Melatonin prevents acetaminophen-induced nephrotoxicity in rats

Abstract

Nephrotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug, and there is no specific treatment for APAP-induced renal damage. It has been reported that reactive oxygen metabolites or free radicals are important mediators of APAP toxicity. In this study, the protective role of melatonin (MLT) on APAP-induced nephrotoxicity was investigated in rats. For this purpose, nephrotoxicity was induced in male Wistar albino rats by intraperitoneal (i.p.) administration of a single dose of 1,000 mg/kg APAP. Some of these rats also received i.p. melatonin (10 mg/kg) 20 min after administration of APAP. The rats were sacrificed 24 h after administration of APAP. Urea and creatinine levels were measured in the blood, and levels of malondialdehyde (MDA) and glutathione (GSH), and glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activity were determined in renal tissue. Serum urea and creatinine levels increased significantly as a result of APAP nephrotoxicity. A significant increase in MDA and decreases in GSH level and GSH-Px, CAT, and SOD activity indicated that APAP-induced renal damage was mediated through oxidative stress. Significant beneficial changes were noted in serum and tissue oxidative stress indicators in rats treated with MLT. These biochemical observations were supplemented by histopathological examination of kidney sections, which revealed that MLT also reduced the severity of APAP-induced histological alterations in the kidney. These results indicate that administration of APAP causes oxidative stress to renal tissue and that MLT protects against the oxidative damage associated with APAP.

Effects of medical ozone therapy on acetaminophen-induced nephrotoxicity in rats

“…The other histopathological findings of APAPinduced nephrotoxicity in rats are tubular epithelial degeneration, proximal tubular vacuolization, cell desquamation, necrosis and cellular debris in the proximal tubules, and cortical interstitial congestion. [1][2][3]5 These results are also consistent with our histopathological findings. The important finding of this study was that ozone therapy ameliorated the APAPinduced severe histopathological renal changes.…”

“…Different studies have shown that APAP-induced renal damage is consistent with acute tubular necrosis. [1][2][3][22][23][24] Direct toxic effect of APAP on capillary wall may be responsible from APAP-induced acute tubular necrosis. The other histopathological findings of APAPinduced nephrotoxicity in rats are tubular epithelial degeneration, proximal tubular vacuolization, cell desquamation, necrosis and cellular debris in the proximal tubules, and cortical interstitial congestion.…”

“…Renal insufficiency occurs in approximately 1-2% of the patients with an overdose of APAP. [1][2][3][4] The main toxicity of APAP is the result of drug metabolism in the liver and other organs. At the pharmacologic doses, APAP is metabolized mostly to inactive compounds via Phase II reactions by conjunction by sulfate and glucuronide.…”

Melatonin and Vitamin C Ameliorate Alcohol-Induced Oxidative Stress and eNOS Expression in Rat Kidney

“…[38][39][40] Yurtcu et al 41 demonstrated that melatonin is a potent antioxidant agent in preventing testicular ischemia-reperfusion (I-R) injury. Ilbey et al 18 found that melatonin treatment inhibited the increase in lipid peroxidation in acetaminopheninduced nephrotoxicity. In another study, Abraham et al 42 reported that melatonin pretreatment reduced methotrexate-induced oxidative stress and alteration in the activity of antioxidant enzymes.…”

“…17 Regarding the protective effect of melatonin on renal alterations various studies have been carried out and it has been found to protect tissues against oxidative damage generated by a variety of toxic agents. 18 Nitric oxide (NO) is a free radical gaseous molecule with a biological half-life of a few seconds. NO is generated from the guanidine nitrogen of L-arginine by three isoforms of nitric oxide synthase (NOS), that is, neuronal NOS (nNOS, NOS-1), endothelial NOS (eNOS, NOS-3), and inducible NOS (iNOS, NOS-2).…”