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Cisplatin (CDDP), an anticancer drug, induces remarkable toxicity in the kidneys of animals and humans and it has been well documented that reactive oxygen species and the renal antioxidant system are strongly involved in acute renal damage induced by CDDP. The aim of the present study was to investigate whether or not the renal antioxidant system plays also an important role in chronic renal damage induced by repeated doses of CDDP (1 mg/kg intraperitoneally twice weekly during 10 weeks in rats). In order to elucidate it, serum creatinine and urea levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS) content, as well as renal superoxide dismutase and glutathione peroxidase activities were measured in the kidney homogenates of chronically CDDP-treated rats and additionally histological studies were performed in the rat kidneys. The chronic treatment with CDDP induced a significant increase in creatinine and urea levels in serum, but the other parameters mentioned above were not significantly modified as compared to the values in nontreated rats. Taking into account these results, we conclude that chronic CDDP administration induces also severe nephrotoxicity, in contrast to CDDP acute application, without any significant modification in the activity of relevant antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, renal glutathione and lipid peroxides, by which the role of the antioxidant system in chronic nephrotoxicity induced by CDDP in rats is uncertain.

BACKGROUND: Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species AIMS: To analyze the effect of ozone administration after cisplatin-induced acute nephrotoxicity. METHODS: Male Sprague-Dawley rats were treated with five intra-rectal applications of ozone/oxygen mixture at 0.36, 1.1 and 1.8 mg/kg after cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were taken off 5 days after cisplatin treatment. Creatinine was measured in the serum and the activities of antioxidant enzymes and thiobarbituric acid reactive substances and glutathione content were analyzed in renal homogenate. RESULTS: Ozone treatment diminished the increase in serum creatinine levels, the glutathione depletion and also reversed the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric reactive substances was decreased by ozone/oxygen mixture applied after cisplatin. CONCLUSION: Intrarectal applications of ozone reversed the renal pro-oxidant unbalance induced by cisplatin treatment by the way of stimulation to some constituents of antioxidant system in the kidney, and thereby it decreased the renal damage.

The protective effects of lobenzarit disodium against the toxicity of allyl alcohol were investigated in vitro using isolated rat hepatocytes and in vivo using mice. In mice, at i.p. doses of 25, 50 and 100 mg/kg lobenzarit significantly decreased the activity of alanine amino transferase (ALT) in serum and the concentration of malondialdehyde (MDA) in liver homogenates, both of which were increased by allyl alcohol at a dose of 64 mg/kg. At concentrations of 0.2 and 0.3 mM, lobenzarit reduced the release of lactate dehydrogenase (LDH) and the levels of malondialdehyde (MDA) induced by 0.4 mM of allyl alcohol in isolated rat hepatocytes. However, lobenzarit did not increase the levels of reduced glutathione (GSH) depleted by allyl alcohol in any of the two experimental models. The protective effects of lobenzarit were dose- and concentration-dependent and they were most obvious when lobenzarit was administered 30 min before allyl alcohol. It is concluded that lobenzarit exerts the observed protective effects most likely by its antioxidant properties.