Cyclosporin (CSA) has been universally used as an immunosuppressant for the management of allotransplantation and autoimmune diseases. However, nephrotoxicity of CSA limits its use to optimum level. Aluminum (Al) is an extensively distributed element in the environment and human exposure to this metal is unavoidable. Recent studies suggest that even a slight impairment of renal function may increase the Al body burden significantly, which may lead to neurotoxicity, nephrotoxicity, osteodystrophy or hypochromic anemia. In the present study, an attempt was made to study the effect of concomitant use of Al and CSA on structure and function of kidney in rats. This study was undertaken in two steps. In the first set of experiments, the effect of single dose of Al (1% Al2(SO4)3 18H2O) on the nephrotoxicity of multiple doses of CSA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) was studied, where as in the second set of experiments the effect of multiple doses of Al (0.25%, 0.5% and 1%) on single dose of CSA (50 mg/kg) was undertaken. Male Sprague-Dawley rats (weighing 230 +/- 20 g) were used in this study. CSA was given once a day by gavage for seven days, where as Al was given in drinking water for the same period. Twenty four hours after the last dose of CSA, animals were sacrificed and blood and kidney were collected for biochemical and histopathological studies. The bio-chemical parameters included blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Al levels. The kidney homogenates were assayed for malondialdehyde (MDA) and lipid hydroperoxides (LPH). Treatment of rats with CSA alone produced dose-dependent structural and functional changes in kidney. Although Al alone failed to produce any deleterious effect on renal function, it significantly increased the bioavailability and nephrotoxicity of CSA. Al also exacerbated CSA induced increase in oxidative stress (as evident by increased MDA and LPH). Thus, the exacerbation of CSA nephrotoxicity by Al may be attributed to increased bioavailability of CSA and excessive generation of free radicals following concomitant use of these drugs.
Numerous clinical reports suggest the beneficial effects of chelation therapy for the treatment of atherosclerosis. However, the results of these studies are inconclusive and controversial. The purpose of this present study was to examine the prophylactic and therapeutic effects of chelation liquid (CHL) in experimental atherosclerosis. Twenty New Zealand white rabbits were fed a 1% cholesterol-supplemented diet for 45 days. In the prophylactic phase of the study subcutaneous 300 mg EDTA + 500 mg magnesium sulphate (MgSO4) injections (five rabbits) and isotonic saline (five rabbits) were given to test and control groups, respectively, along with cholesterol rich diet. The CHL treatment ameliorated the rise of serum cholesterol and serum triglyceride concentrations, lowered serum calcium concentrations and reduced the aortic atheroma. In the therapeutic phase of the experiment the cholesterol diet was stopped and the remaining 10 animals were returned to normal diet. Five of these rabbits were given CHL injections and other five animals were given isotonic saline injections for 121 days. Although the level of cholesterol and triglyceride were not significantly different in the two groups, the serum calcium concentration and the percentage of the area of flate aortic specimen occupied by atheroma were significantly lower in the CHL treated rabbits as compared to controls. It is concluded that CHL injections have a definite prophylactic effect on atherogenesis in the cholesterol-fed rabbit, and may have some therapeutic value in the regression phase. Further confirmatory studies are suggested.
Background:The use of cyclosporin (CsA) in the presence of other nephrotoxic drugs poses a great challenge to physicians. This study was designed to address the effect of concomitant administration of mercury and cyclosporin on nephrotoxicity of rats.Methods-Male Spragu~-Dawley rats (weighing 230 + 20 g) were divided into the following 8 groups of 7 animals each: group 1, control; group 2, mercury alone; group 3, cyclosporin 12.5 mg/kg; group 4, cyclosporin 25 mg/kg; group 5, CsA50 mg/kg; group 6, CsA 12.5 mg/kg + mercury; group 7, CsA 25 mg/kg + mercury; and group 8, CsA 50 mg/kg + mercury. Mercury (1 mg/kg) was given by subcutaneous injection, and CsA, by oral gavage; drugs were given once a day for 7 days. Twenty-four hours after the last dose of drugs, the animals were killed, and blood samples were assayed for BUN, serum creatinine, and CsA levels. The left kidney was analyzed for malondialdehyde, lipid hydroperoxides, vitamin E, and glutathione levels, and histopathologic analysis was done on the right kidney.
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