Protective effects of certoparin sodium, a low molecular weight heparin derivative, in experimental atherosclerosis

Background: 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: Mate 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(R); 300 mug/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. (C) 2003 Elsevier B.V. All rights reserved.