Department of Biological Sciences

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Subject: search.filters.subject.Low molecular weight heparin

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    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.
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    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.
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    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.
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    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.
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    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.
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    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.
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    Exogenous Heparin-Derivative Affords Protection Against Lipid Anomalies and Apoptotic DNA Damage in Experimental Atherogenesis
    (Bentham Science, 2006) Deepa, P.R.
    Background: Cholesterol-induced cytotoxicity is a major cause of death of macrophages in atherosclerotic lesions. Apoptosis, or programmed cell death, plays an important role in atherogenesis. A deficiency of endogenous heparin activity is said to result in hypertriglyceridemia, hypercholesterolemia and enhanced atherogenesis, which is corrected on injecting exogenous heparin. In the current study, a low-molecular-weight heparin (LMWH), certoparin was tested for its influence on lipid anomalies and apoptotic damage in early atherogenesis. Methods and results: Two groups of 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 two weeks. One group was left untreated, the other was administered certoparin (300 μg/day/rat) commencing on day 8 and continued for a week. At the end of the two-week experimental period, we found significant elevation in plasma free cholesterol, free fatty acids and phospholipids (p < 0.001) and abnormal accumulation of cholesterol, triglycerides and phospholipids in the cardiac, hepatic and renal tissues of the untreated animals. Administration of LMWH subcutaneously corrected the lipid anomalies partly by restoring the altered activities of lipid metabolizing enzymes including total lipase, lipoprotein lipase, lecithin: cholesterol acyl transferase, cholesterol ester synthetase and hydrolase. Protein aggregation and cross- linking were observed in the cardiac microsomes of the untreated hypercholesterolemic group, along with significantly high malondialdehyde levels (p < 0.001); LMWH treatment afforded considerable protection against this oxidative damage. DNA fragmentation analysis and comet assay revealed marked DNA damage in the cardiovascular tissue from the untreated hypercholesterolemic group that was minimized by subcutaneous LMWH treatment. Conclusion: The LMWH, certoparin favorably modulates lipid disturbances in cardiac, hepatic and renal tissues, exerts a beneficial effect on oxidative changes and the structural integrity of cardiac microsomal membranes, and protects against apoptotic DNA damage in the cardiovascular tissue, thereby proving to be potentially anti-atherogenic.