Effect Of Melatonin On Ketamine-related Renal Injury By Increasing Nrf2 And HO-1 In Rats

Objective: To elucidate the efficacy and possible mechanism of melatonin in treating ketamine-induced kidney damage involved in oxidative stress injury.Methods: Thirty-two male rats were distributed into the following four groups according to the random number table method: received a single daily intraperitoneal injection of normal saline(CON group),30 mg/Kg ketamine(KET group),5mg/Kg melatonin(MLT group)and 30 mg/Kg ketamine combined with 5mg/Kg melatonin(KET+MLT group)for a period of 12 weeks.After 12 weeks,all these rats were anesthetized and the renal were taken out for further study.Content of SOD,GSH-PX and MAD were studied to evaluate renal oxidative injury.TUNEL assay was performed to detect cell apoptosis.Histological staining were also performed to assess the damaged of renal tissue.The expression level of HO-1 were measured by western blotting.Results: After 12 weeks of peritoneal injection,it shown a decreased trend compared to other groups that the weight of rats in KET group.The urination time of rats in the KET group were increased compared to other groups.The KET group was a significantly increased in the level of serum creatinine,blood urea nitrogen,and MDA.The KET group shown many cells apoptosis and inflammatory cell infiltration,along with a significantly decreased the content of SOD,GSH-PX.There were a lot of glomerular atrophy and interstitial cord in renal tissue.Melatonin treatment resulted in reduction of parameters of oxidative stress,cell apoptosis,along with reduced the aggravation of renal interstitial fibrosis.Furthermore,melatonin treatment attenuated glomerular atrophy and inflammatory cell infiltration,it was also found a significantly increase the level of Nrf2 and HO-1 in the renal tissue after melatonin treatment.Conclusions: Our study indicates that ketamine induced glomerular atrophy and inflammatory cell infiltration,along with cell apoptosis.Melatonin treatment could ameliorate ketamine induce renal oxidative injury and i mproves kidney function via activation of the Nrf2 and HO-1 expression.