The pathophysiologic mechanisms leading to acute ischemic renal failure are not completely understood. Melatonin, a compound with well-known antioxidant properties, reduces IR-induced renal injury. The purpose of the present study was to investigate the changes in levels of tumor necrosis factor (TNF)-alpha, IL-beta, and IL-6 in postischemic reperfused renal tissue, and to determine whether the protective effect of melatonin is related the modulation of the production of these inflammatory molecules. Male Wistar albino rats were unilaterally nephrectomized and subjected to 1 hr of renal pedicle occlusion followed by 2 hr or 24 hr of reperfusion. Melatonin (10 mg/kg, i.p.) or vehicle was administrated at 10 min prior to ischemia. After 24 hr of the reperfusion, following decapitation, kidney samples were taken both for histologic examination and for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, total antioxidant capacity (TAC), total oxidative stress (TOS), creatinine, and blood urea nitrogen (BUN). These were measured in serum samples. TNF-alpha, IL-beta, and IL-6 were measured in kidney samples after 2 hr of reperfusion. IR caused a significant increase in renal MDA, MPO, TOS, creatinine, and BUN while decrease TAC without any change in TNF-alpha, IL-beta, and IL-6 levels. Melatonin treatment reduced the biochemical indices without any change in the cytokine levels and ameliorated histopathologic alterations induced by IR. The protective effect of melatonin on IR-induced renal injury is related to its antioxidant properties but not to proinflammatory cytokines.

BACKGROUND: The aim of this study was to investigate the effects of lycopene (Lyc) on methotrexate (Mtx) induced liver toxicity in rats. METHODS: Twenty-eight male Sprague-Dawley rats were divided into four equal groups: control, Lyc, Mtx and Mtx-L: Control group: Rats were given only the vehicle. Lyc group: Rats were given Lyc (10 mg/kg) with corn oil by oral gavage for ten days. Mtx group: Rats were injected intraperitoneally with a single dose of 20 mg/kg of Mtx and given corn oil by oral gavage. Mtx-L group: Rats were post-treated with Lyc (10 mg/kg) for ten days after a single dose of Mtx (20 mg/kg). RESULTS: Mtx administration increased histopathological damage, TNF-α, IL-1β, TOS, TAS and OSI levels in tissues; AST, ALT levels in the blood. Sinusoidal dilatation, infl ammatory cell infi ltration and congestion were signifi cantly improved in the Mtx-L aon histopathologic examination of the rats. In Mtx-L group that were treated at the Lyc, TNF-α and IL-1β levels of liver tissue were decreased signifi cantly compared to Mtx group whereas the decrease in OSI was not signifi cant. Lyc treatment improved the AST and ALT values in Mtx-L group. But only AST improvement was signifi cant. CONCLUSIONS: The results of this study revealed that Lyc might be useful in protecting the liver from injury due to Mtx in rats by reducing the increased proinfl ammatory cytokine levels (Tab. 4, Fig. 1, Ref. 44). Text in PDF www.elis.sk.

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This study was performed to evaluate the effect of melatonin on methanol-induced liver injury. We evaluated the levels of malondialdehyde (MDA), protein carbonylation (PC), myeloperoxidase (MPO) activities and to assess lipid peroxidation, protein oxidation, neutrophil accumulation and nitrite which is a stable end product of nitric oxide respectively. We also studied superoxide dismutase, catalase, and glutathione peroxidase activities of liver tissue to evaluate the changes in the antioxidant status. Histopathological alterations were also determined. The experiment was performed on Wistar rats, which received intragastric 3 g/kg methanol as a 50% solution in isotonic saline once. After 6 and 24 hr all the drug received and intoxicated rats were killed under anesthesia. Pretreatment with melatonin (10 mg/kg) decreased the MDA levels significantly, restored the PC levels to the control, prevented the increase of nitrite level and MPO activity significantly and reversed to the control levels, prevented the reduction in all of the antioxidant enzyme activities. Additionally in melatonin treated group piecemeal necrosis, lobular lytic necrosis, and portal inflammation returned to normal histologic appearances when compared with methanol administration. In conclusion, melatonin has protective effects against methanol-induced hepatic injury.

Methotrexate (Mtx), used for its anticancer and immunsuppresive properties, is known to be a nephrotoxic agent. We aimed to investigate the effects of lycopene (Lyc) alone or combined with melatonin (Mel) on Mtxinduced nephrotoxicity since both of these agents have antioxidant and anti-inflammatory effects. Nephrotoxicity was induced by intraperitoneal administration of methotrexate at a dose of 20 mg/kg. Treatment both with Lyc alone and Lyc combined with Mel provided significant reduction in tumor necrosis factor-alpha, interleukin 1-beta and ceruloplasmin levels in Mtx administered rats. Hovewer, Lyc combined with Mel provided a significant reduction also in NO levels. Hstopathological examination showed that there was an obvious improvement in the degenerative changes compared to Mtx administrated group with the Lyc combined Mel group giving best protection. In conclusion Lyc alone and combined with Mel provided significant improvement against renal damage caused by Mtx, preseumably via antioxidant and anti-inflammatory activities.