Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Physiology

Background & aim: cisplatin as antineoplastic drug belonging to platinum family has a severely nephrotoxic and neurotoxic side effects. L-carnitine (LC) is a natural compound with a nephro-protective and neuro-protective activity in several experimental studies. In the present study we have tested the hypothesis that LC may have a protective role on cisplatin induced nephropathy and neuropathy. Experimental Design: 48 male rats, 8 weeks old, their weight varies between 180 - 200 grams, randomly divided into 6 groups, each group included 8 rats. Control group. LC group received L- carnitine (250mg/kg body weight by daily intra-peritoneal injections for 3 days). Nephropathy group received single injection of cisplatin (20mg/kg body weight intra-peritoneal). Neuropathy group received daily intra {u2013} peritoneal injections of 2.3mg /kg body weight cisplatin within two rounds of 5 days with 5 {u2013} day break in between. LC Treated nephropathy group, L carnitine was injected IP after single injection of cisplatin for 3 days. LC Treated neuropathy group, L carnitine was injected IP after the second round of 5 days for 3 days On last day of experiment, serum levels of urea and creatinine were measured from each rat on the following groups (control group, LC group, nephropathy group and LC treated nephropathy group) then the rats were sacrificed by cerebral concussion and their kidneys were excised, weighted and processed for electron microscope for structural assessment. In addition, the distal end of rat tail of the following groups (control group, LC group, neuropathy group and LC treated neuropathy group) was immersed in hot water bath then latency for rat to withdrawal its tail was measured to assess the sensory affection of peripheral nerves then the right sciatic nerve was dissected and placed in moist chamber to be stimulated by power lab device for assessment of nerve conduction velocity and the amplitude of action potential Results: LC treatment after cisplatin injection was able to significantly reduce the nephrotoxicity and neurotoxicity of cisplatin in rat models. Serum urea and creatinine after treatment with LC were significantly reduced in comparison to the cisplatin group, in addition, LC treatment showed significantly increase in the physiological parameters of sciatic nerve. In conclusion: L-carnitine has a beneficial effect on improvement of neuropathy and nephropathy induced by cisplatin via its anti {u2013}oxidant effect and its ability to scavenge free oxygen radicals

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