الفهرس | Only 14 pages are availabe for public view |
Abstract Cisplatin is a platinum compound with an antineoplastic activity. It has been widely and successfully used against a variety of human tumors. Unfortunately, a major obstacle to more wide spread use of cisplatin is the persistence of sever toxic side effects, The major dose-limiting factor of the drug is nephrotoxicity which is dose dependent and apparently irreversible in some cases, increased oxidative stress and apoptosis have been implicated in the cardiotoxicity and nephrotoxicity that limits the clinical use of cisplatin as an anti-tumoral drug, The present study was performed to: I) To study the protective role of a-lipoic acid against cisplatin-induced cardiotoxicity and nephrotoxicity 3) To investigate the possible effect of a-lipoic acid on the antitumor activity of cisplatin in mice bearing Solid and Ascites Ehrlich carcinoma, Malerats were used and classified into four groups, First group received a single LP, injection with normal saline (Control), The second group received LP, cisplatin injection (1 Omg ! kg). Third group received a single LP, injection of a-lipoic acid (100 mg / kg). Fourth group received LP. cisplatin injection (10 mg / kg) and LP, injection of a-lipoic acid (100 mg / kg) 30 minutes prior to cisplatin. Twenty-four hours after the last treatment, Blood samples were withdrawn from the rats of each group by heart puncture after light ether anesthesia using test tubes, Serum was separated, and then the following parameters were determined: 1. Determination of Blood Urea Nitrogen (BUN), II. Determination of Serum Creatinine (Cr). 111. Determination of serum lactate dehydrogenase (LDH) , IV, Determination of serum creatine kinase (CK). Heart and both kidneys were immediately dissected out and freed .from adjacent tissues, washed in cold saline to remove any excess blood, blotted to dry on filter paper and then weighed prior to biochemical analysis, Each organ was homogenized in cold saline to give 20% homogenate, The homogenate was used for determine lipid peroxides (MDA), reduced glutathione (GSH), nitric oxide (NO) and superoxide dismutase (SOD), In addition, DNA-fragmentation and caspase-3 activation in kidney tissues were studied, Finally, parts of the kidneys and heart were used for histopathological examination |