The cytoprotective role of a low-molecular-weight heparin fragment studied in an experimental model of glomerulotoxicity.
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 microg/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.
Department of Medical Biochemistry, DrAL Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Perinkulam Ravi
PR
Deepa
Palaninathan
P
Varalakshmi
D000818:Animals; D000900:Anti-Bacterial Agents; D000925:Anticoagulants / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood / Q000652:urine; D004317:Doxorubicin; D006025:Glycosaminoglycans / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D000975:Antioxidants; D006025:Glycosaminoglycans; D006495:Heparin, Low-Molecular-Weight; D010446:Peptide Fragments; D014527:Uric Acid; D004317:Doxorubicin; D003404:Creatinine