Protective effect of aminoguanidine against cyclosporine induced nephrotoxicity and hepatotoxicity in rats: histological and biochemical study

Cyclosporine A [CsA] is a potent and effective immuno-suppressive agent used to prevent rejection in organ transplant surgery and autoimmune diseases. Its use is frequently accompanied by nephrotoxicity and hepatotoxicity. The present study was designed to investigate the possible protective effect of aminoguanidine on Cyclosporine induced nephrotoxicity and hepatotoxicity in male albino rats. A total of sixty healthy adult male albino rats were used divided into four equal groups in this study. Group I rats served as control treated with distilled water orally only, group II was treated with CsA in a dose of 25mg/kg orally daily for 21 days, group III treated with CsA concurrently with aminoguanidine in doses of 25 and 20mg/kg orally daily for 21 days respectively and group IV was treated with olive oil orally [vehicle for CsA]. Rats were sacrificed 24 hs after last dose, blood, kidney and liver samples were taken. Histopathological examination by light and electron microscopic, immunohistochemistry for active caspase-3 were done. Besides, biochemical measurement; serum nitric oxide level and kidney and liver functions tests were done. CsA oral administration for 21 days significantly increased serum nitric oxide level impaired the renal and hepatic function tests and markedly distorted the renal and hepatic morphology in light and electron microscopic examination. Aminoguanidine administration improved serum nitric oxide level, kidney and liver function tests and preserved renal and hepatic morphological structures. Aminoguanidine has a protective effect against Cyclosporine induced nephrotoxicity and hepatotoxicity

Therapeutic efficacy of alpha lipoic acid in combination with succimer against lead-induced oxidative stress, hepatotoxicity and nephrotoxicity in rats

Lead toxicity is a worldwide health problem due to continuous exposure of the population to lead in the environment especially workers in industries. It affects many body organs especially the liver and kidneys. The aim of this study is to investigate and compare the therapeutic potential of alpha lipoic acid [ALA] when it is administrated alone and in combination with succimer or dimercaptosuccinic acid [DMSA] against lead induced oxidative stress, hepatotoxicity and nephrotoxicity. Seventy five healthy male albino rats were used divided into 5 equal groups. Group [1] the control group was administrated distilled water orally for 6 weeks. Group [II] rats were given lead acetate [0.2%] in drinking water for 5 weeks and distilled water only orally during the 6[th] week. Group [III, IV and V] rats were given lead acetate [0.2%] in drinking water for 5 weeks followed by DMSA in a dose of 20 mg/kg body weigh/day intraperitoneally [i.p.] alone, ALA in a dose of 25 mg/kg body weigh/day [i.p.] alone and both drugs in combination during the 6[th] week only respectively. Rats were sacrificed after six weeks. Blood lead level serum lipid peroxides [TBARS], serum total antioxidant [TAG] and serum nitric oxide [NO] levels were measured. Also Liver function tests [serum alkaline phosphatase, glutamic oxalacetic transaminase and glutamaic pyruvic transaminase] were measured. In addition, kidney function tests [serum urea, creatinine and uric acid] were done. Results showed an increase in the mean of blood lead level, increase serum TBARS levels, decrease serum TAG and NG levels and increase levels of liver and kidney function tests in lead treated group. Treatment with DMSA alone resulted in reduction of blood lead levels, improvement of serum NG level but not decrease serum TBARS level and moderate decrease in the elevated liver and kidney function test parameters. Rats treated with ALA alone showed no reduction in the elevated blood lead levels, but decreased serum TBARS and improved serum NO, TAG levels, liver and kidney function tests. Rats treated with DMSA and ALA concurrently showed decrease in blood lead levels, decrease serum TBARS, increase serum NO and TAG levels to near normal level and corrected liver and kidney function tests. In conclusion administration of ALA has beneficial effect as thiol-mediated antioxidant function when given to occupationally exposed workers to lead and during treatment of lead poisoning with DMSA as it increases its efficacy