Department of Biological Sciences
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Item Favourable influence of low molecular weight heparin in mitigating the peroxidative membrane damage induced by a cytotoxic agent and an atherogenic diet(Sage, 2003) Deepa, P.R.The present study is aimed to demonstrate the protective effect of a heparin derivative, low molecular weight heparin (LMWH) against erythrocyte membrane injury. Two models serve to induce membrane lipid peroxidative damage, namely a potent cytotoxic agent, adriamycin and a hypercholesterolemic atherogenic diet. Two groups of male Wistar rats (1409-10 g) received a single intravenous injection of adriamycin (ADR, 7.5 mg/kg), while two other groups were fed an atherogenic diet comprising a supplementation of 4% cholesterol, 1% cholic acid and 0.5% thiouracil (CCT diet) for 2 weeks. For each of the above two groups, LMWH (Troparin; 300 mg/day per rat subcutaneously) treatment commenced on day 8 and continued for a week. One group was maintained as the normal control group, and another group that received only LMWH treatment was designated as the LMWH drug control group. Erythrocyte membrane was isolated and assayed for its cholesterol levels, lipid peroxidation and ATPases activity. The activities of antioxidant enzymes were assessed in the haemolysate. The findings of the study were that both adriamycin and the atherogenic diet produced elevated membrane cholesterol levels and lipid peroxidation. The membrane ATPases suffered loss in activity. Accentuated oxidative stress was marked by rise in the activities of antioxidant enzymes (SOD, catalase and GPx). LMWH intervention reverted these changes thereby normalizing the membrane composition and function. The membrane protective effect of LMWH is illuminated by this work.Item The cytoprotective role of a low-molecular-weight heparin fragment studied in an experimental model of glomerulotoxicity(Elsiever, 2003) Deepa, P.R.Abnormal glomerular glycosaminoglycan metabolism is involved in the onset of the morphological and functional aberrations of glomerulopathies. In the present study, a heparin derivative, low-molecular-weight heparin, was tested for its ability to afford renoprotection in an established model of experimental glomerulopathy. Two groups of male albino rats of the Wistar strain (140±10 g) received a single intravenous injection of adriamycin (7.5 mg/kg) to induce glomerulopathy, and one of them received low-molecular-weight heparin (Certoparin Sodium, Troparin®; 300 μg/day/rat s.c.) treatment, commencing on day 8, for a week. Urinary protein/creatinine ratio, serum albumin, urea, uric acid and creatinine clearance were evaluated. Renal cell injury was assessed in terms of renal tissue lactate dehydrogenase, aminotransferases (aspartate and alanine transaminases) and alkaline phosphatase activities, as well as renal antioxidant status (superoxide dismutase, catalase and glutathione peroxidase, reduced glutathione, vitamins E and C). The kidney tissue was subjected to histopathologic examination. Low-molecular-weight heparin significantly reduced proteinuria and improved creatinine clearance and serum albumin levels in the rats with glomerulopathy. The significant rise in serum uric acid in the rats with glomerulopathy was reversed by low-molecular-weight heparin. Altered tissue enzyme activities in response to injury, oxidative stress challenged renal antioxidant system and abnormal renal histology were observed in the untreated nephrotic rats, while low-molecular-weight heparin treatment protected the nephrotic rats against these changes. Thus, in this study, low-molecular-weight heparin was evaluated for its role in combating glomerular injury, on the basis of some salient biochemical parameters, oxidative injury indices and histologic picture. The ability of low-molecular-weight heparin to restore glomerular anatamo-functional features in this nephrotoxic condition illuminates its multi-faceted renoprotective role.Item Protective effect of low molecular weight heparin on oxidative injury and cellular abnormalities in adriamycin-induced cardiac and hepatic toxicity(Elsiever, 2003) Deepa, P.R.The aim of the present work is to evaluate the effect of a heparin derivative, low molecular weight heparin (LMWH) on the biochemical changes, tissue peroxidative damage and abnormal antioxidant levels in adriamycin (ADR) induced cardiac and hepatic toxicity. Male Wistar rats (140±10 g) were divided into four groups: untreated control (group I), ADR group (a single dose intravenous injection of 7.5 mg/kg ADR—group II), LMWH control (300 μg/day per rat s.c. for 1 week—group III) and ADR plus LMWH group (7.5 mg/kg ADR on day 1 of study period followed by LMWH treatment, 300 μg/day per rat commencing on day 8 and continued for a week. At the end of the 2-week experimental period, all animals were terminated. Cellular damage was assessed in terms of serum and tissue lactate dehydrogenase (LDH), aminotransferases and alkaline phosphatase (ALP) activities. Creatine phosphokinase (CPK) was assessed in the serum and heart tissue. The role of LMWH in altering the oxidative stress in ADR-induced toxicity was evaluated on the basis of its influence on cardiac and hepatic lipid peroxidation and antioxidant status (enzymatic and non-enzymatic)—superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), reduced glutathione (GSH), α-tocopherol (Vitamin E) and ascorbate (Vitamin C). LMWH administration to ADR-induced rats prevented the rise in serum and tissue levels of LDH, aminotransferases and ALP, while these parameters were significantly elevated in the ADR group in comparison with the control group. Cardiotoxicity indicated by rise in serum CPK in the ADR group was attenuated by LMWH treatment in group IV. LMWH decreased the cardiac and hepatic lipid peroxidation induced by ADR. Histologic examination revealed that the ADR-induced deleterious changes in the heart and liver tissues were offset by LMWH treatment. Restoration of cellular normalcy accredits LMWH with cytoprotective role in adriamycin-induced cardiac and hepatic toxicity.Item Salubrious effect of low molecular weight heparin on atherogenic diet-induced cardiac, hepatic and renal lipid peroxidation and collapse of antioxidant defences(Springer, 2003) Deepa, P.R.The present work showcases the distressing picture of oxidative stress in the cardiac, hepatic and renal tissues, in an experimental model based on early phase atherogenesis. The protection rendered by LMWH intervention forms part of the same study. Male Wistar rats of 140 ± 10 g were categorized as four groups. One group served as untreated control and another as LMWH drug control group. Two groups were fed a hypercholesterolemic atherogenic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil; CCT diet) for 2 weeks; one of these groups received LMWH treatment of 300 μg/day/rat for 7 days. The biochemical index of tissue lipid peroxidation (LPO) was assessed in terms of MDA formation. Heart, liver and kidney tissues of CCT-diet fed rats showed significantly elevated levels of LPO. In the early phase atherosclerotic group, we observed abnormal changes in the activities/levels of tissue enzymic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic (reduced glutathione, ascorbate and α-tocopherol) antioxidants. We report normalized LPO levels and antioxidant defences in the atherogenic rats treated with LMWH. Thus the present study highlights the hepatic, cardiac and renal oxidative changes induced by experimental atherogenesis, and the protection rendered by LMWH treatment in atherosclerotic cardiovascular conditions.Item Protective effects of certoparin sodium, a low molecular weight heparin derivative, in experimental atherosclerosis(Elsiever, 2004) Deepa, P.R.The association of atherosclerosis and hypercholesterolemia is well known. Hypercholesterolemic diet-induced atherogenesis is a widely accepted experimental model that is amenable to exploration of both the disease as well as therapeutic interventions. We evaluated the role of low molecular weight heparin (LMWH) in modulating the early biochemical changes in atherogenesis. Methods: Male Wistar rats (140±10 g) were fed an atherogenic diet comprising of normal rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil (CCT diet) for 2 weeks. While one of the CCT diet-fed group served as the untreated pathologic model, the other group received LMWH (Certoparin sodium, Troparin®; 300 μg/day/rat s.c.) treatment, commencing on day 8 and continued for 1 week. Results: Decreased concentrations of serum albumin and increased serum urea, uric acid and creatinine concentrations were normalized by LMWH treatment. The atherogenic diet induced abnormal rise in the activities of lactate dehydrogenase, aminotransferases and alkaline phosphatase, as well as the high serum cholesterol and triglyceride concentrations were restored to near control values in the treated group. LMWH administration prevented the hypertrophic cardiac histology and fatty changes in the liver in early atherogenesis. Conclusion: The present study encapsulates the early cellular abnormalities in the heart, liver and kidney tissues of atherogenic diet fed rats. Treatment with LMWH affords considerable protection to the tissues challenged by hypercholesterolemia, evidenced by its correction of lipemia and restoration of serum and tissue indices of injury, to normalcy. LMWH intervention minimized the atherogenic diet-induced histopathological lesions in heart, liver and kidney tissues.Item Atheroprotective effect of exogenous heparin-derivative treatment on the aortic disturbances and lipoprotein oxidation in hypercholesterolemic diet fed rats(Elsiever, 2005) Deepa, P.R.The present work explores the myriad of biochemical and cellular changes that are featured in the early stages of atherosclerosis; if unchecked these changes lead to the complicated atherosclerotic plaque formation. The influence of a low-molecular-weight heparin derivative on the aortic aberrations and lipoprotein oxidation has been assessed in an experimental model of hypercholesterolemic atherogenesis.Item Beneficial cardio-renovascular effects of a low-molecular-weight heparin-derivative on adriamycin-induced glycosaminoglycanuria and tissue lipid abnormalities(Elsiever, 2005) Deepa, P.R.The present work includes a study on the glycosaminoglycanuric condition induced by adriamycin (ADR, a chemotherapeutic agent) and the accompanying secondary hyperlipidemia, wherein the treatment with a low-molecular-weight heparin-derivative (LMWH), certoparin, is evaluated for its protective role (if any) on these parameters. Two groups of male albino rats of the Wistar strain (140 ± 10 g) received a single intravenous injection of adriamycin (7.5 mg/kg), and one of these groups was treated with a low-molecular-weight heparin-derivative (Certoparin Sodium, Troparin®; 300 μg/day/rat s.c.), commencing on day 8, for a week. Urinary total glycosaminoglycans excretion of the untreated ADR-induced group was found to increase on the 8th and the 15th days of observation, when compared with the controls. The LMWH treatment commencing on day 8 resulted in minimising the glycosaminoglycans (GAGs) excretion by day 15 (p < 0.001). Plasma, cardiac, hepatic and renal lipids (cholesterol, triglycerides and phospholipids) showed a sharp increase in the pathologic group, along with a rise in plasma LDL and VLDL cholesterol and drop in HDL cholesterol levels, paralleled by abnormal activities of the enzymes involved in lipid metabolism. LMWH treated group showed a normalised lipid profile and the activities of the lipid-metabolising enzymes was close to that of controls. It is concluded herein that adriamycin administration resulted in severe nephropathy manifested by increased glycosaminoglycanuria and abnormal lipid metabolism, and that LMWH treatment afforded substantial protection by restoring glomerular structure and function, and normalised the plasma and tissue lipid levels, lipoprotein profile and the activities of lipid-metabolising enzymes.Item Biochemical evaluation of the inflammatory changes in cardiac, hepatic and renal tissues of adriamycin-administered rats and the modulatory role of exogenous heparin-derivative treatment(Elsiever, 2005) Deepa, P.R.The aim of the present work is to evaluate the role of a heparin derivative, low molecular weight heparin (LMWH), certoparin on the inflammatory changes in adriamycin (ADR) cytotoxicity on a biochemical basis. Male Wistar rats (140 ± 10 g) were divided into four groups: untreated control, ADR group (a single dose intravenous injection of 7.5 mg/kg ADR), LMWH control (300 μg/(day rat) s.c. for 1 week) and ADR plus LMWH group (7.5 mg/kg ADR on day 1 of study period followed by LMWH treatment, 300 μg/(day rat) commencing on day 8 and continued for 1 week). At the end of the 2-week experimental period, biochemical assessment of the inflammatory status was carried out in the plasma, cardiac, hepatic and renal tissues. Increased concentrations of plasma C-reactive protein (CRP) and fibrinogen indicated severe inflammation in the ADR cytotoxic rats. These acute-phase inflammatory markers diminished significantly in the LMWH treated group, when compared with the cytotoxic group (p < 0.001). Tissue damage was marked by elevated levels of plasma and tissue hexose, hexosamine, hexuronic acid and sialic acid, which were reversed on LMWH administration (p < 0.001). The activities of lysosomal enzymes was measured in the experimental groups, and it was observed that the ADR induced rats showed a marked increase in the enzymic activities, while LMWH treated rats revealed normal activities. The present study throws light on the inflammatory changes in the ADR-challenged heart, liver and kidney tissues, and projects the biochemical basis for the anti-inflammatory property of the LMWH, certoparin.Item Influence of a low-molecular-weight heparin derivative on the nitric oxide levels and apoptotic DNA damage in adriamycin-induced cardiac and renal toxicity(Elsiever, 2006) Deepa, P.R.The spectrum of the anti-apoptotic potential of heparin is currently under scrutiny in various tissues and under various pathological situations. In this study, the role of a low-molecular-weight heparin derivative (LMWH), certoparin in adriamycin-induced oxidative DNA damage has been evaluated in the cardiac and renal tissues. Two groups of male albino rats of the Wistar strain (140 ± 10 g) received a single intravenous injection of adriamycin (7.5 mg/kg), and one of them received low-molecular-weight heparin (Certoparin Sodium, 300 μg/day/rat s.c.) treatment, commencing on day 8, continued for a week. The nitrosative stress in ADR cytotoxicity is indicated by the 1.51-fold cardiac and 2.36-fold renal increase in reactive nitrogen species (RNS), while LMWH treatment restores normalcy (p < 0.001). The influence of LMWH on the pro-inflammatory and pro-apoptotic cytokine, TNF-α was studied. Renal and cardiac levels of TNF-α showed a significant rise (p < 0.001) in the ADR cytotoxic group, while the TNF-α values departed towards control levels in the LMWH treated group (p < 0.001). DNA damage indicated by the fragmentation pattern (agarose gel electrophoresis) and the significantly increased comet tail length (p < 0.001) observed after alkaline single cell gel electrophoresis confirmed the toxicity induced by ADR on DNA in the untreated group. In the LMWH-treated group, the observation of intact DNA band after agarose gel electrophoresis, and the finding of comet tail length being comparable with that of the control substantiated the protection rendered by the LMWH, certoparin. In short, the results suggest that the low-molecular-weight heparin derivative, certoparin exerts beneficial effects on the nitrosative status, and on the biological macromolecules as DNA and curtails the rise of the pro-apoptotic and pro-inflammatory cytokine, TNF-α in the cardiac and renal tissues.Item Favourable modulation of the inflammatory changes in hypercholesterolemic atherogenesis by a low-molecular-weight heparin derivative(Elsiever, 2006) Deepa, P.R.In the hypercholesterolemic state, the net result of combined oxidative and nitrosative stress is a pro-inflammatory phenotype that is manifested as increased adhesion molecule expression, enhanced leucocyte trafficking, and increased vascular permeability. The present work explores the inflammatory aspects of hypercholesterolemic atherogenesis, and also evaluates the role of a low-molecular-weight heparin derivative (LMWH), Certoparin, on a biochemical basis.