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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.