Effect of atorvastatin and ascorbic acid on the gastrocnemius muscle of hyperlipidemic rats: histological, histochemical and biochemical study

Atorvastatin is a member of statins family which are widely used for the treatment of hyperlipidemia and coronary heart disease. Unfortunately, it induces muscle toxicity that limits its use. The present work was performed to evaluate the extent of these toxic effects and to clarify the role of high dose of vitamin C [ascorbic acid] in controling hyperlipidemia and as a protective against statin myotoxicity. This study was conducted on forty adult male albino rats divided into one control group [eight rats] and four experimental groups [eight rats each]. Animals of the control group received normal standard diet while the experimental groups were fed hyperlipidemic diet alone [Group I], or with an additional i.p 200 mg vitamin C [Group II], oral 2.5 mg atorvastatin [Group III] and both vitamin C and atorvastatin [Group IV]. After three months, total lipids and creatine phosphokinase were measured. Histological and histochemical changes in gastrocnemius muscle were also evaluated. The biochemical results established efficacy of both drugs [atorvastatin and vit C] either alone or combined in the treatment of hyperlipidemia by a highly significant reduction of total cholesterol, triglycerides [TG], low-density lipoprotein [LDL] and elevation of high-density lipoprotein [HDL]. CPK showed a highly significant increase in group III only. This group [Group III] showed variable degrees of cellular affection and myopathic changes in the form of splitting, fragmentation, loss of transverse striations, and focal areas of degeneration with vacuoles and cellular infiltration. Peripheral accumulation of glycogen and an apparent decrease in succinic dehydrogenase activity were also seen. Electron microscopy revealed that the myofibrils were not in register and showed many vacuoles, irregular nuclei and mitochondrial affection. Active fibroblasts and an apparent increase in collagen fibers were also seen. The last group [IV] which received vit. C in addition to atorvastatin showed few degenerated muscle fibers with many new regenerating ones. The regenerating fibers showed numerous, central or peripheral nuclei. The glycogen content was patchy among muscle fibers and there was an apparent increase in succinic dehydrogenase enzyme activity. From the above findings, it could be concluded that vitamin C is a safe and effective lipid-lowering drug alternative to statins. It can also protect against statin myotoxicity

Elucidacion de los mecanismos de fototoxidad inducida por farmacos / Mechanisms of phototoxicity induced by pharmaceutical products

First of all some general concepts are given on phototoxic activity of pharmaceutical products which full fill the structural characteristics required to decompose by light and to cause biological damage, either themselves, their photoproducts or the products of their metabolism. These considerations are important due to the fact that this field of research is fairly new. Next, a review is given on recent research carried out in this laboratory on the photochemistry and phototoxicity of fibric acid and their derivatives and finally a refc5r cview is made as well on the photochemistry and phototoxicity of antibacterial quinolones. Mechanisms are postulated for the photochemical decomposition of the substances investigated and possible mechanism for the in vitro activity at cellular level are also presented