...funding research, sharing discoveries.
A. S. Alhomida
Professor of Biochemistry and Vice Dean for Graduate Studies and Scientific Research, King Saud University, College of Science, Riyadh, Saudi Arabia
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International journal of toxicology 29(3)
Increased urinary excretion of carnitine and acylcarnitine by mercuric chloride is reversed by 2,3-dimercapto-1-propanesulfonic acid in rats.
This investigation was aimed to study the effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on mercuric chloride (HgCl(2))-induced alterations in urinary excretion of various carnitine fractions including free carnitine (FC), acylcarnitine (AC),... expand abstract and total carnitine (TC). Different groups of Wistar male rats were treated with HgCl(2) at the doses of 0.1, 0.5, 1.0, 2.0, and 3.0 mg/kg body weight, and the animals were sacrificed at 24 hours following HgCl(2) injection. A separate batch of animals received HgCl(2) (2 mg/kg) with or without DMPS (100 mg/kg) and sacrificed at 24 or 48 hours after dosing. Administration of HgCl(2) resulted in statistically significant and dose-dependent increase in the urinary excretion of FC, AC, and TC in rats. However, the ratio of urinary AC:FC was significantly decreased by HgCl(2). Pretreatment with DMPS offered statistically significant protection against HgCl(2)-induced alterations in various urinary carnitine fractions in rats. collapse abstract
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Lipids in health and disease 9
The changes in various hydroxyproline fractions in aortic tissue of rabbits are closely related to the progression of atherosclerosis.
BACKGROUND: The most important function of collagen and elastin is to induce several mechanical parameters which are known to play a dominant role in governing mechanical properties of the blood vessels. The aortic tissue of rabbit is one of the impo... expand abstractrtant sources of collagen and elastin. The effects of high fat diet (HFD) on the hydroxyproline (Hyp) fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits have not been documented before. The present study was undertaken to investigate the changes in Hyp fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits during the progression of atherosclerosis. The atherosclerotic model used in this study was the New Zealand white rabbit (male; 12 weeks old). Twenty five rabbits were individually caged, and divided into control group (NOR; n = 10) and HFD group (CHO; n = 15). The control group was fed (100 g/day) of normal (NOR) diet for a period of 15 weeks. The HFD group was fed normal diet supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period of time. RESULTS: We found that the TC, LDLC, and TG (mg/dl) were significantly (p < 0.001) increased in HFD rabbits compared with control rabbits with percentage normalized changes of 1198%, 1591%, and 710%, respectively. The peptide-bound Hyp in the serum was significantly (P < 0.05) increased in HFD rabbits compared with control rabbits with percentage normalized change of 517% while it significantly (P < 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 65%. The protein-bound Hyp in the serum was significantly (P < 0.01) increased in HFD rabbits compared with control rabbits with percentage normalized change of 100%; the protein-bound Hyp in the aortic tissues of control rabbits was 235.30 +/- 55.14 (Mean +/- SD) while it was not detectable (ND) in HFD rabbits. Total serum Hyp showed no significant (P < 0.05) change in HFD rabbits compared with control rabbits while it was significantly (P < 0.05) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73%. The total collagen was significantly (p < 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73% which was supported by histological study. CONCLUSIONS: These results suggest that percentage decrease in various Hyp fractions in aortic tissue of HFD rabbits are closely related to percentage decrease of collagen content in aortic tissues of HFD rabbits. These results also suggest that it may be possible to use the changes in various Hyp fractions in aortic tissues of rabbits as an important risk factor during the progression of atherosclerosis. collapse abstract
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Clinical biochemistry 2010 Feb; 43(4-5)
Significant impact of pace of eating on serum ghrelin and glucose levels.
OBJECTIVES: To study the effect of normal versus slow eating on serum ghrelin, glucose, insulin, and C-peptide levels in healthy subjects from Riyadh, Saudi Arabia. DESIGN AND METHODS: The specified breakfast meal was served on two randomized occasio... expand abstractns to 24 healthy volunteers to eat with a normal pace or at a slow rate. Venous blood samples were collected at 7 time points for biochemical analysis. RESULTS: The slow ingestion of meals resulted in a significant increase in blood glucose and ghrelin levels as compared to normal pace of eating. CONCLUSIONS: Normal eating speed appears to be beneficial for maintaining the optimal blood glucose and ghrelin levels. collapse abstract
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Toxicological sciences : an official journal of the Society of Toxicology 2009 Apr; 109(1)
Neurovestibular toxicities of acrylonitrile and iminodipropionitrile in rats: a comparative evaluation of putative mechanisms and target sites.
This investigation was aimed to study the effects of individual and concomitant exposures of the two nitrile compounds, the industrially important acrylonitrile (ACN; 5, 15, 45 mg/kg/day) and the positive control iminodipropionitrile (IDPN; 100 mg/kg... expand abstract/day) in rats. The six treatment groups were 1 (control), 2 (ACN 5), 3 (ACN 15), 4 (ACN 45), 5 (IDPN), and 6 (IDPN + ACN 15). Both the drugs were started on the same day and continued for 9 days (IDPN was given daily 30 min before ACN but stopped a day earlier). The animals were daily observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex, and contact inhibition of righting reflex. There was no dyskinetic behavioral abnormality in the animals treated with any of the three doses of ACN whereas all the rats in IDPN alone treated group developed clear symptoms of excitation, circling, and chorea syndrome (ECC syndrome) on day 9. Concomitant treatment of rats with ACN significantly attenuated the severity of IDPN-induced behavioral deficits. Administration of ACN significantly depleted glutathione (GSH) in striatum, hippocampus and cerebral cortex; IDPN significantly reduced the GSH only in striatum. The anterior striatum showed intense tyrosine hydroxylase (TH) expression in IDPN alone treated rat as compared to control and ACN alone treated rat. Cotreatment with ACN reduced the intensity of TH immunostaining in IDPN-treated rats. Administration of IDPN alone caused massive loss of vestibular sensory hair cells in the crista ampullaris whereas the sensory epithelium appeared intact in ACN alone treated groups. The animals receiving the combination of ACN and IDPN showed comparatively less degeneration of sensory hair cells than IDPN alone group. These findings suggest that ACN and IDPN produce different behavioral effects that are exerted through entirely different mechanisms; the nervous and vestibular systems appear to be the major target sites of these toxins, respectively. collapse abstract
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Bioinformatics and biology insights 2
Effects of feeding periods of high cholesterol and saturated fat diet on blood biochemistry and hydroxyproline fractions in rabbits.
Hypercholesterolemia and hypertriglyceridemia are considered as important risk factors during the atherosclerotic process. The aim of the present investigation was to study the total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high ... expand abstractdensity lipoprotein (HDL), triglyceride (TG), platelet levels and hydroxyproline fractions during the pathogenesis of atherosclerosis. For this purpose, twenty five 12-weeks, New Zealand white male rabbits, were purchased, individually caged, and divided into either control group or cholesterol-fed group. The control group (n = 10) was fed 100 g/day of normal diet, ORC-4 (Oriental Yeast Co. Ltd., Tokyo, Japan) for a period of 15 weeks. The cholesterol-fed group (n = 15) was fed a high cholesterol and saturated fat diet of ORC-4 containing 1% cholesterol plus 1% olive oil (100 g/day) for periods of 5 (group 1), 10 (group 2) and 15 (group 3) weeks. Blood sample from each animal was taken at the end of the experimental period for the biochemical analysis. The results of the present study showed that TC, LDLC, TG, HDLC and platelets were significantly (P < 0.01) increased in cholesterol-fed rabbits as compared with control rabbits. The serum hydroxyproline (Hyp) in rabbits belonging to group 1 showed no significant alteration when compared to control group. Group 2 rabbits showed a significant increase of 103% (P < 0.01) and 100% (P < 0.001) in free and protein-bound hydroxyproline fractions respectively when compared to control rabbits. However, there was no significant change in peptide-bound and total serum hydroxyproline levels as compared to the control group (P > 0.05). There was no significant (P > 0.05) decrease of free serum hydroxyproline in group 3 rabbits when compared to control rabbits. On the other hand, group 3 rabbits showed a significant increase in peptide-bound and protein-bound Hyp by 517% (P < 0.05) and 100% (P < 0.01) respectively when compared to control rabbits. However, total serum Hyp in group 3 rabbits showed no significant (P > 0.05) change when compared to control rabbits. These results suggest that feeding rabbits high cholesterol and saturated fat diet for feeding periods of 5, 10 and 15 weeks induced significant change in TC, LDLC, HDL, TG, platelet levels and various Hyp fractions in serum without any significant change in the total Hyp content. collapse abstract
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Clinical and experimental medicine 2006 Sep; 6(3)
Fluctuations in fasting blood glucose and serum fructosamine in pregnant women monitored on successive antenatal visits.
Fasting blood glucose (FBG) and serum fructosamine are simple and commonly used tests for monitoring diabetes mellitus. Unfortunately, both these parameters are associated with high error rates and therefore used with caution in high-risk populations... expand abstract. Setting high cut-off values for these parameters increases the sensitivity but at the cost of poor specificity (more false positives). Continued efforts have been made to evaluate the efficacy of FBG and fructosamine, singly or in combination, in avoiding a large number of unnecessary oral glucose tolerance tests (OGTT). Therefore, to better understand their time-course trends, we analysed FBG and c-fructosamine in 211 blood samples from 51 Saudi pregnant women during their multiple (> or =3) antenatal visits. The mean+/-standard deviation of FBG and c-fructosamine were 5.22+/-1.07 and 2.22+/-0.25 mmol/l respectively with a significant correlation between their individual values. Using the FBG cut-off >5.3 mmol/l, 19 subjects were classified as hyperglycaemic; this frequency was reduced to 1 when a FBG cut-off of >7.0 mmol/l was used. Combined values of FBG (>5.3 mmol/l) and c-fructosamine (>2.5 mmol/l) filtered 6 high-risk subjects with a prediction of gestational diabetes mellitus (GDM). Analysis of variance revealed high within-group variance for FBG. These fluctuations were also confirmed by higher coefficient of variations (CVs) for FBG (13.27%) as compared to c-fructosamine (5.49%). The CVs of FBG were not correlated with those of corresponding CVs of c-fructosamine (R = 0.007, P = 0.962), indicating that the fluctuations in FBG were independent of fluctuations in c-fructosamine. These findings clearly suggest that the paired values of FBG and c-fructosamine would be more advantageous than their individual values in filtering high-risk patients on whom OGTT should be performed. collapse abstract
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Medical science monitor : international medical journal of experimental and clinical research 2006 Feb; 12(3)
Effect of mercuric chloride on urinary excretion of free hydroxyproline.
BACKGROUND: The present study was undertaken to study the effect of mercuric chloride (HgCl2) on the collagen metabolism in rats and the protective effect of 2, 3-dimercapto-1-propane sulfonic acid (DMPS) in HgCl2-treated rats. MATERIAL/METHODS: The ... expand abstractexperimental groups studied were (i) a control group (ii) rats injected with a single intraperitoneal (ip) dose of 2 mg of HgCl2/kg body weight (HgCl2-treated group, n=10 rats), (iii) Rats injected with a single dose (ip) of 100 mg of DMPS/kg body weight (DMPS group, n=10 rats), (iv) rats injected with a single dose (ip) of 100 mg of DMPS/kg body weight followed by a single dose (ip) of 2 mg of HgCl2/kg body weight 1 hour after a 100-mg DMPS injection (DMPS + HgCl2-treated group, n=10 rats). Half of the rats from each group were sacrificed after 24 hours and the other half after 48 hours of treatment. RESULTS: A dose of 2.0 mg HgCl2/kg body weight caused an impairment of glomerular function, which was reflected by significant increases in the levels of serum creatinine and serum urea nitrogen in HgCl2-treated rats compared with control rats. Administration of 2.0 mg of HgCl2/kg body weight significantly increased urinary excretion of free hydroxyproline in HgCI2-treated rats compared with the control rats, reflecting increased collagen breakdown. CONCLUSIONS: Administration of DMPS one hour before HgCl2 treatment caused the restoration of altered parameters to near normal levels. collapse abstract
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Molecular and cellular biochemistry 2005 Feb; 271(1-2)
Effect of mercuric chloride on various hydroxyproline fractions in rat serum.
Mercuric chloride (HgCl2) disturbs the collagen metabolism in the body which is reflected by altered hydroxyproline fractions in the serum. The aim of the present investigation was to study the effect of HgCl2 treatment on various hydroxyproline (Hyp... expand abstract) fractions in rat serum and the effect of 2,3-dimercapto-1-propane sulfonic acid (DMPS) treatment on serum Hyp fractions in HgCl2 treated rats. Other parameters studied included body weight, food intake, water intake and kidney weight. Doses of HgCl2 used were 0.1, 0.5, 1.0, 2.0, 3.0 mg/kg body weight and that of DMPS was 100 mg DMPS/kg body weight. All the doses of HgCl2 used caused significant (p < 0.01) alterations in free, peptide-bound and protein-bound Hyp in the serum when compared with control rats but a dose of 2 mg/kg body weight caused significant (p < 0.001) alteration even in the total serum Hyp when compared to control rats. Administration of DMPS prior HgCl2 treatment of rats sacrificed 24 h after the treatment caused a significant decrease of 52% (p < 0.01) in free Hyp when compared to similar HgCl2 treated rats. DMPS treatment with HgCl2 also caused an increase of 61% (p < 0.001) and 114% (p < 0.001) in peptide- and protein-bound Hyp respectively, when compared to HgCl2 treated rats sacrificed 24 h after mercuric chloride and DMPS treatment. Administration of DMPS followed by HgCl2 to rats which were sacrificed 48 h later caused no significant change in the total and free Hyp when compared to HgCl2 treated rats which were sacrificed 48 h after the treatment. But there was a significant decrease of 40% (p < 0.001) in peptide-bound Hyp and an increase in of 77% (p < 0.001) in protein-bound Hyp when compared to HgCl2 treated rats sacrificed 48 h after the treatment. The present study shows that HgCl2 treatment caused significant alterations in serum Hyp fractions reflecting disturbed composition of connective tissues which were not reversed by DMPS treatment. collapse abstract
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Journal of biochemistry and molecular biology 2003 Mar; 36(2)
Investigation into the distribution of total, free, peptide-bound, protein-bound, soluble- and insoluble-collagen hydroxyproline in various bovine tissues.
Collagen is a family of proteins which consists of several genetically distinct molecular species and is intimately involved in tissue organization, function, differentiation and development. The purpose of this study was to investigate the concentra... expand abstracttion of different hydroxyproline (Hyp) fractions viz., total, free, peptide-bound, protein-bound, soluble- and insoluble-collagen hydroxyproline (Hyp) in various bovine tissues. Results showed that liver had the highest concentration of free Hyp followed by kidney, brain, spleen, lungs, muscle and heart. Liver also had the highest concentration of peptide-bound collagen Hyp followed by kidney, heart, spleen, lungs, brain and muscle. The concentration of protein-bound collagen Hyp was highest in the liver, followed by kidney, spleen, lungs, muscle, brain and heart. Total Hyp was highest in the liver, followed by kidney, spleen, brain, heart, muscle and lungs. Liver also had significantly high concentration of collagen as compared to other tissues examined (P<0.001). Spleen had the significantly higher concentration of soluble-collagen Hyp when compared to other tissues (P<0.001). This was followed by heart, muscle, lungs, brain, kidney and liver. Heart had the highest concentration of insoluble-collagen Hyp followed by lungs, kidney, liver, muscle, spleen and brain. The variation among the insoluble-collagen Hyp concentration of heart and muscle, spleen and brain was significant (P<0.001). We speculate that these differences could be due to the variation in turn over of rate of collagen metabolism in this species. collapse abstract
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In vivo (Athens, Greece) 16(1)
Antagonist effect of chloroquine and tumor necrosis factor on hepatic oxidative stress and antioxidant defense in normal and Plasmodium yoelii nigeriensis-infected mice.
BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Tumor necrosis factor (TNF) has been implicated in the pathogenesis of malaria by production of reactive oxygen species. Chloroquine... expand abstract is a traditionally used antimalarial and has been postulated to inhibit TNF secretion during malaria infection. OBJECTIVE: The study the comparative effect of chloroquine and TNF treatment on hepatic oxidative stress and antioxidant defense indices in normal and P. y. nigeriensis-infected mice. MATERIALS AND METHODS: The mice were divided into six groups, each consisting of four to six animals. They were normal mice, normal mice treated with chloroquine, normal mice treated with TNF-alpha, P. y. nigeriensis-infected mice, P. y. nigeriensis-infected mice treated with chloroquine and P. y. nigeriensis-infected mice treated with TNF-alpha. RESULTS: Chloroquine treatment of the normal mice caused no significant alterations in hepatic oxidative stress and antioxidant defense indices while TNF treatment of normal mice caused a significant decrease in hepatic superoxide dismutase. Chloroquine treatment of P. y. nigeriensis-infected mice caused a decrease in blood parasitemia which was accompanied by restoration of altered indices to near normal levels. However, TNF treatment of P. y. nigeriensis-infected mice had no effect on blood parasitemia but caused a significant increase of hepatic xanthine oxidase and lipid peroxidation and a decrease in the activity of hepatic superoxide dismutase. CONCLUSION: Exogenous TNF acts synergistically with P. y. nigeriensis infection to generate oxidative stress in the host and also causes an impairment of the antioxidant defense enzyme SOD, while chloroquine treatment reduces the severity of malaria infection by decreasing the blood parasitemia and also perhaps by inhibiting the TNF release. collapse abstract
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Journal of biochemistry, molecular biology, and biophysics : JBMBB : the official journal of the Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) 2002 Mar; 6(2)
Hydroxyproline distribution in the plasma of various mammals.
We have investigated the presence of total, free, protein-bound and peptide-bound hydroxyproline (Hyp) in the plasma of different mammals viz., camel, bovine, sheep, human, rabbit and rat. Total Hyp was significantly highest in human followed by rabb... expand abstractit, rat, bovine, sheep and camel (P<0.001). Free Hyp was significantly highest in human followed by rabbit, rat, camel, bovine and sheep (P<0.001). However, the protein-bound Hyp content was significantly highest in rat followed by bovine, human, camel, rabbit and sheep (P<0.001). Peptide-bound Hyp was significantly highest in human plasma followed by sheep and rabbit (P<0.001). No peptide-bound Hyp was detected in the plasma of camel, bovine or rat. In the human plasma, peptide-bound Hyp constituted 60% of the total plasma Hyp, followed by protein-bound Hyp, which was 35% of the total, Hyp and free Hyp, which was 15% of the total plasma Hyp. In the sheep plasma peptide-bound Hyp constituted about 50% of total Hyp followed by protein-bound (40% of the total Hyp) and free Hyp, which formed 10% of total Hyp. In the rabbit plasma protein-bound Hyp constituted 50% of the total Hyp fraction, followed by peptide-bound and free, which constituted about 30 and 20%, respectively, of the total Hyp fraction of the plasma. Peptide-bound Hyp formed 92, 84 and 82% of the total plasma Hyp in rat, camel and bovine, respectively. Free Hyp constituted about 8% of the total plasma Hyp in rat and 18% of total Hyp in bovine and camel, respectively. The causes of the significant variations in different collagen structure and composition with respect to the different species examined are not known, however, these variations may results from differences in turn-over rate of Hyp in those species. collapse abstract
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Molecular and cellular biochemistry 2002 Feb; 232(1-2)
Methemoglobin reductase activity and in vitro sensitivity towards oxidant induced methemoglobinemia in swiss mice and beagle dogs erythrocytes.
The NADH methemoglobin-reductase (EC 1.6.2.2) is mainly responsible for the maintenance of hemoglobin in its reduced and active state. The present study reveals the comparative status of this enzyme in normal Beagle dogs, rats, mice, mastomys and ham... expand abstractsters erythrocytes. The spectrophotometric and electrophoretic determinations showed that the above mentioned enzyme was deficient in the Beagle dog's erythrocytes. Furthermore, in vitro studies on the sensitivity of these rodents and Beagle dogs hemolysate towards oxidants, like primaquine and sodium nitrate, depicted a higher level of methemoglobin formation in the Beagle dogs hemolysate as compared to that of the rodent species. The deficiency of methemoglobin reductase in Beagle dogs erythrocytes could be responsible for their increased sensitivity towards oxidant induced methemoglobinemia. collapse abstract
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Archives of medical research 32(5)
Oral theophylline changes renal carnitine palmitoyltransferase activity in rats.
BACKGROUND: Carnitine plays a critical role in lipid metabolism. Carnitine deficiency may adversely affect the oxidation of fatty acids and further aggravate abnormal lipid metabolism. Our objective was to investigate the effect of theophylline on th... expand abstracte activity of carnitine palmitoyltransferase (CPT) in renal tissues of rats for 5-week-interval treatments. METHODS: The study was a randomized, controlled animal study. Theophylline was given at 100 mg/kg body weight (b.w.)/day and effects were monitored after a treatment period of between 1 and 5 weeks. RESULTS: Theophylline treatment caused a significant increase in renal CPT activity as compared to either control or placebo groups. Moreover, the results showed positive correlations between the renal concentration of long-chain acylcarnitine (LC), activity of CPT, urinary excretion of acylcarnitine (AC), and plasma concentration of LC (p <0.01), respectively. CONCLUSIONS: The observed changes in activity of renal CPT might be due to the result from theophylline-enhanced mobilization of lipid from adipose tissues that consequently stimulated an increased carnitine transport into the renal tissues to form palmitoylcarnitine groups for subsequent beta-oxidation inside the mitochondria. Thus, these accumulations of palmitoylcarnitine groups in mitochondria may increase the catalytic action of CPT. collapse abstract
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Journal of enzyme inhibition 16(2)
Evaluation of theophylline-stimulated changes in carnitine palmitoyltransferase activity in skeletal muscle and liver of rats.
The effect of theophylline treatments on the activity of carnitine palmitoyltransferase (CPT) in skeletal muscle and the liver of rats was investigated. Theophylline was administered at 100 mg/kg bw/day and effects were monitored after a treatment pe... expand abstractriod that lasted between a week and five weeks. Results showed that a significant increase in the activity of CPT was observed in skeletal muscle of theophylline-treated groups as compared to either control or placebo groups. However, there was no significant change in the activity of CPT in the hepatic tissues of theophylline-treated groups. The observed discrepancies in activity of CPT might be due to the presence of two isoenzymes, the muscle type (M-CPT) and liver type (L-CPT); it is possible that theophylline affects only M-CPT activity. collapse abstract
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In vivo (Athens, Greece) 15(1)
Effect of poly ICLC treatment on hepatic oxidative stress and antioxidant defense indices in Plasmodium yoelii nigeriensis infected mice.
BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) are important mediators of tissue injury during malaria infection. OBJECTIVE: To study the status of h... expand abstractepatic oxidative stress and antioxidant defense indices during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and poly ICLC treatment of normal and P. y. nigeriensis infected Swiss albino mice. METHODS: Mice were divided into four groups viz., 1. Normal mice, 2. Normal mice treated with poly ICLC (5 mg/kg body weight, i.p.), 3. P. y. nigeriensis infected mice and 4. P. y. nigeriensis infected mice treated with poly ICLC (5 mg/kg body weight, i.p.). RESULTS: P. y. nigeriensis infection caused a significant increase in hepatic oxidative stress indices viz., xanthine oxidase and lipid peroxidation. This was accompanied by a significant increase in antioxidant defense indices viz., reduced glutathione (GSH), glutathione reductase while superoxide dismutase and catalase showed a significant decrease with respect to normal mice. Poly ICLC treatment of P. y. nigeriensis infected mice did not cure blood parasitemia. However, poly ICLC treatment of normal and P. y. nigeriensis resulted in an increased generation of hepatic oxidative stress and an associated increase in the antioxidant defense indices. CONCLUSION: poly ICLC therapy alone is not sufficient to treat the malaria infection caused by multiple drug resistant strain of P. y. nigeriensis. Therefore there is a need to develop newer antimalarias which can act alone or in combination with traditional antimalarials to be effective against drug resistant malarial parasite. collapse abstract
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Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 2001 Jun; 129(4)
Changes in rodent-erythrocyte methemoglobin reductase system produced by two malaria parasites, viz. Plasmodium yoelii nigeriensis and Plasmodium berghei.
The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin and methemoglobin in blood. Exposure of red blood cells to oxidative stress (pathological/physiological) may cause impairment to this equilibrium.... expand abstract We studied the status of erythrocytic methemoglobin and the related reductase system during Plasmodium yoelii nigeriensis infection in mice and P. berghei infection in mastomys. Malaria infection was induced by intraperitoneal inoculation with 10(6) infected erythrocytes. The present investigation revealed a significant decrease in the activity of methemoglobin reductase, with a concomitant rise in methemoglobin content during P. yoelii nigeriensis infection in mice erythrocytes. This was accompanied with a significant increase in reduced glutathione and ascorbate levels. The activity of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase increased with a progressive rise in parasitemia. However, no methemoglobin or associated reductase activity was detected in normal and P. berghei-infected mastomys. P. berghei infection in mastomys resulted in an increase in the level of reduced glutathione and ascorbate in erythrocytes, and also in the activity of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase. These results suggest that antioxidants/antioxidant enzymes may prevent or reduce the formation of methemoglobin in the host and thereby protect the host from methemoglobinemia. collapse abstract
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Drug and chemical toxicology 2001 Apr; 24(2)
Effect of beta-arteether treatment on erythrocytic methemoglobin reductase system in Plasmodium yoelii nigeriensis infected mice.
BACKGROUND: The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin (Hb) and methemoglobin (MetHb) in blood. Exposure of red blood cells to an oxidative stress (pathological/physiological) may cause imp... expand abstractairment in this equilibrium. OBJECTIVE: The status of MetHb and the related reductase system was studied during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and beta-arteether treatment in mice. METHODS: Mice were divided into four groups. Normal group, normal mice treated with beta-arteether, P. y. nigeriensis infected mice and P. y. nigeriensis infected mice treated with beta-arteether. RESULTS: The present investigation revealed a marked decrease in the activity of MetHb reductase, with concomitant rise in MetHb levels during P. y. nigeriensis infection in mice erythrocytes (P < 0.001) as compared to normal mice. However, the activities of the associated enzymes viz., lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase were found to be increased with progressive rise in parasitemia. beta-Arteether treatment (12.5 mg/kg body weight) of infected mice (parasitemia 20-25%) from day 5 of post infection resulted in complete clearance of parasitemia on day 7 of post infection, which was accompanied by restoration of all the altered above mentioned indices to near normal levels as compared to infected mice (P < 0.001). CONCLUSION: These results suggest that there is a marked impairment of methemoglobin and methemoglobin reductase system during P. y. nigeriensis infection in mice. beta-Arteether treatment of infected mice resulted in complete clearance of parasitemia which also caused the restoration of methemoglobin and methemoglobin reductase system to near normal levels. collapse abstract
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Molecular and cellular biochemistry 2000 Dec; 217(1-2)
A study on distribution of different hydroxyproline fractions in the bovine ocular tissues.
The purpose of this study was to determine the content of total, free, peptide-bound, protein-bound, soluble- and insoluble collagen hydroxyproline (Hyp) in tissues of bovine eye. The results show that lens had the highest content of free Hyp. This w... expand abstractas followed by cornea, retina, iris and aqueous humor. The difference between the Hyp content of lens and iris (p < 0.01) and aqueous humor (p < 0.001) was significant. The peptide-bound Hyp was highest in iris followed by cornea, ciliary body, sclera, lens, aqueous humor and retina. Significant differences (p < 0.001) was observed between the concentration of peptide-bound Hyp of iris and ciliary body, sclera, lens, aqueous humor and retina. Protein-bound Hyp was highest in iris, followed by ciliary body, sclera, cornea, lens, retina and aqueous humor. The difference between the protein-bound Hyp levels of iris and sclera, cornea, lens, retina and aqueous humor was significant (p < 0.001). No peptide-bound and protein-bound Hyp was detected in vitreous humor. Iris had the highest content of total Hyp. This was followed by cornea, ciliary body, sclera, lens, retina, vitreous humor and aqueous humor. The difference in the Hyp content of iris with ciliary body, sclera, lens, retina, vitreous humor and aqueous humor was significant (p < 0.001). Cornea had significantly (p < 0.001) higher content of soluble- and insoluble-collagen Hyp as compared to other tissues. This was followed by ciliary body, sclera, lens, iris and retina. Iris had the highest content of collagen. This was followed by cornea, ciliary body, sclera, lens, retina, vitreous humor and aqueous humor. The difference in the collagen content of iris with ciliary body, sclera, lens, retina, vitreous humor and aqueous humor was significant (p < 0.001). collapse abstract
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In vivo (Athens, Greece) 14(4)
Studies on erythrocytic methemoglobin reductase systems in Plasmodium yoelii nigeriensis infected mice.
BACKGROUND: The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin and methemoglobin in blood. Exposure of red blood cells to oxidative stress (pathological/physiological) causes an impairment in this ... expand abstractequilibrium. OBJECTIVE: To study the status of methemoglobin and the related reductase system during Plasmoidum yoelii nigeriensis (P. y. nigeriensis) infection in mice. METHOD: Mice were divided into two groups viz., normal mice and P. y. nigeriensis infected mice. Malaria infection was induced by intraperitoneal inoculation of 10(6) infected erythrocytes. RESULTS: The present investigation revealed significant decrease in the activity of methemoglobin reductase, with concomitant rise in methemoglobin content during P. y. nigeriensis infection in mice erythrocytes. This was accompanied with a significant increase in reduced glutathione and ascorbic acid levels. Also the activities of the associated enzymes viz., lactate dehydrogenase, glucose-6-Phosphate dehydrogenase and glutathione reductase were found to increase with progressive rise in parasitemia. CONCLUSION: P. y. nigeriensis infection in mice results in impairment of methemoglobin reductase in the host. collapse abstract
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Cell biochemistry and function 2000 Nov; 18(4)
Investigation of total, free, peptide-bound, protein-bound, soluble and insoluble collagen hydroxyproline content in tissues from the Arabian camel (Camelus dromedarius).
This study was conducted to determine the concentration of total, free, peptide-bound, protein-bound, soluble and insoluble collagen hydroxyproline (Hyp) in tissues from the Arabian camel (Camelus dromedarius). Results indicated that there were signi... expand abstractficant differences in the concentration of total, free, peptide-bound, protein-bound, soluble and insoluble collagen Hyp in various tissues (P < 0.01). Camel kidney showed a significantly high concentration of total, free, peptide-bound and protein-bound Hyp and collagen content as compared to other tissues examined (P < 0.01). Kidney also showed a significantly high concentration of soluble collagen Hyp as compared to other tissues examined (P < 0.01). However, the concentration of insoluble collagen Hyp was significantly high in liver when compared to other tissues (P < 0.01). These variations may result from differences in the collagen structure and/or composition in this species. collapse abstract
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Drug and chemical toxicology 2000 Oct; 23(4)
Effect of tumor necrosis factor on hepatic oxidative stress and antioxidant defense indices in normal and Plasmodium yeolii nigeriensis infected mice.
BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide along with endogenously produced tumor necrosis factor (TN... expand abstractF) have been implicated in the pathogenesis of malaria. OBJECTIVE: Study the effect of TNF on hepatic oxidative stress and antioxidant defense indices in normal and P. y. nigeriensis infected mice. METHODS: Mice were divided into four groups. Normal group, TNF treated group, P. y. nigeriensis infected group, and P. y. nigeriensis infected mice treated with TNF group (250 microg/kg body weight, i.p.). RESULTS: TNF treatment of normal mice caused a highly significant decrease in hepatic superoxide dismutase (SOD) while changes in other oxidative stress and antioxidant defense indices were nonsignificant. On the other hand, TNF treatment of P. y. nigeriensis infected mice caused a highly significant increase in hepatic xanthine oxidase, lipid peroxidation and a significant decrease in hepatic SOD with respect to infected mice. CONCLUSION: These results suggest that exogenous TNF acts synergistically with P. y. nigeriensis infection to generate oxidative stress in the host and also causes an impairment of antioxidant defense enzyme such as superoxide dismutase. collapse abstract
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Biochemical pharmacology 2000 Aug; 60(4)
Kinetics of human acetylcholinesterase inhibition by the novel experimental Alzheimer therapeutic agent, tolserine.
Characterization of the kinetic parameters of tolserine, a novel acetylcholinesterase (AChE) inhibitor of potential in the therapy of Alzheimer's disease, to inhibit purified human erythrocyte AChE was undertaken for the first time. An IC(50) value w... expand abstractas estimated by three methods. Its mean value was found to be 8.13 nM, whereas the IC(100) was observed to be 25.5 nM as calculated by single graphical method. The Michaelis-Menten constant (K(m)) for the hydrolysis of the substrate acetylthiocholine iodide was found to be 0.08 mM. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the partial non-competitive type. The value of K(i) was estimated as 4.69 nM by the primary and secondary replots of the Dixon as well as secondary replots of the Lineweaver-Burk plot. Four new kinetic constants were also investigated by polynomial regression analysis of the relationship between the apparent K(i) (K(Iapp)) and substrate concentration, which may open new avenues for the kinetic study of the inhibition of several enzymes by a wide variety of inhibitors in vitro. Tolserine proved to be a highly potent inhibitor of human AChE compared to its structural analogues physostigmine and phenserine. collapse abstract
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Proceedings of the National Science Council, Republic of China. Part B, Life sciences 2000 Jun; 24(3)
Thermodynamic analysis of human retinal acetylcholinesterase inhibition using an anti-Alzheimer's drug, tacrine, through the development of a dual substrate and temperature model.
The present study determines the energy parameters, such as the Gibb's free energy change (deltaG), enthalpy change (deltaH), heat of activation (deltaH*), entropy change (deltaS), temperature coefficient (Q10) and activation energy (Ea), of human re... expand abstracttinal acetylcholinesterase (AChE, EC 3.1.1.7) inhibition by tacrine. The stereo-frequency collisions factor (PZ, the number of sterically and energetically favorable collisions occurring between tacrine and AChE) was also studied in this investigation. Tacrine significantly increased the value of deltaG, deltaH, deltaH*, Q10, Ea and PZ factor, and decreased the value of deltaS for AChE. Since there is no known report on the inhibition of human retinal AChE by tacrine, these results were compared with the reported values for the energy parameters of camel retinal and chicken brain AChE inhibition by an anti-cancer drug, cyclophosphamide. The uniqueness of this approach lies in the development of the 'dual substrate and dual temperature' model, which may open up a new, more efficient avenue for the study of various enzyme catalyzed reactions. collapse abstract
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In vivo (Athens, Greece) 13(6)
Status of hepatic oxidative stress and antioxidant defense systems during chloroquine treatment of Plasmodium yoelii nigeriensis infected mice.
BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide have been implicated in the pathogenesis of malaria. OBJEC... expand abstractTIVE: Study the effect of the chloroquine treatment on hepatic oxidative stress and antioxidant defense indices in multiple drug resistant (MDR) P. y. nigeriensis infected mice. METHODS: Mice were divided into four groups. Normal group, chloroquine treated normal group, P. y. nigeriensis infected group, and P. y. nigeriensis infected mice treated with chloroquine group (10 mg/kg body weight, i.p.). RESULTS: P. y. nigeriensis infection resulted in a significant decrease in the hepatic protein levels and caused a significant increase in the hepatic oxidative stress indices such as xanthine oxidase and lipid peroxidation and also an increase in the antioxidant defense indices viz, reduced glutathione (GSH), and glutathione reductase, but a significant decrease in superoxide dismutase (SOD) and catalase. The chloroquine treatment of P. y. nigeriensis (MDR strain) infected mice did not completely cure blood parasitemia, but resulted in a decrease of blood parasitemia. This was accompanied by decrease in hepatic oxidative stress indices and an associated change in the antioxidant defense indices towards normalization. CONCLUSION: Chloroquine therapy alone is not sufficient to treat the malaria infection caused by multiple drug resistant strain of P. y. nigeriensis. Therefore, there is a need to develop newer antimalarials which could act alone or in combination with traditional antimalarials to be effective against drug resistant malarial parasites. collapse abstract
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British journal of biomedical science 56(3)
Effect of haemodialysis on peripheral lymphocyte carnitine levels in patients with chronic pyelonephritis.
The effect of haemodialysis on peripheral blood lymphocyte levels of total carnitine (TC), free carnitine (FC) and acylcarnitine (AC), and on the ratio of AC to FC, is investigated in 20 healthy subjects (13 men and seven women) and 27 patients (10 m... expand abstracten and 17 women) with chronic pyelonephritis. The mean predialysis peripheral lymphocyte levels of TC, FC and AC were not significantly different from those in the healthy controls (P > 0.05). However, after haemodialysis, peripheral lymphocyte levels of TC, FC and AC decreased significantly, compared with either predialysis (TC: 40%, FC: 37%, AC: 52%) or healthy controls (TC: 61%, FC: 63%, AC: 50%) (P < 0.01). Furthermore, after haemodialysis the AC/FC ratio was significantly higher, compared with either predialysis (41%) or healthy controls (38%) (P < 0.01). collapse abstract
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