Single and chronic administration of ciprofibrate or of ciprofibrate-glycinate in male Fischer 344 rats: Comparison of the effects on morphological and biochemical parameters in liver and blood

摘要: Fibrates lead to a reduction of serum triglycerides and cholesterol in hyperlipidemic patients. Their therapeutic use, however, can be associated with adverse effects like gastrointestinal disorders, myalgia, myositis hepatotoxicity. Large doses even cause hepatocellular carcinoma rodents. Additionally, interactions the biotransformation other compounds at cytochrome P450 (CYP) system have been observed. Thus, discovery new derivatives less these side is great interest. In present study single (10 mg/kg body weight) or 4-week (1 10 weight daily) oral administration ciprofibrate newly synthesized ciprofibrate-glycinate was investigated adult male Fischer 344 rats. Serum lipid concentrations were distinctly decreased after but only slightly chronic two fibrates, whereas liver parameters revealed slight concentration time dependent Histologically, hypertrophy, an eosinophilia, reduced glycogen content also apoptosis hepatocytes Effects more pronounced treatment application higher dosage. All CYP enzymes induced manner. Resulting mediated monooxygenase oxidase activities showed dependency both on enzyme induction hepatotoxic effects. With no parameter major differences seen between ciprofibrate-glycinate. investigations noticeable advantages over its parent compound ciprofibrate.