A Preliminary Study On Ketamine Abuse Induced Bladder Oxidative Stress Injury Of Rats

Objective:To investigate the bladder oxidative stress injury of SD rats that induced by ketamine abuse and explore the role of melatonin on this process.Methods:Thirty male SD rats, which all 2 months old and weights 200±20 gram, were randomly divided into 3 groups:NS group, HK group and MT group. They were received intraperitoneal injection of saline,100 milligram per kilogram of ketamine and 100 milligram per kilogram of ketamine plus 10 milligram per kilogram of melatonin once a day, respectively. All these rats were weighed twice a week and the dose of drugs were changed according to their weights.After 12 weeks of peritoneal injection, all these rats were anesthetized.The bladders has been taken out for further study and HE staining, Masson staining,TUNEL assay, immunohistochemistry staining and transmission electron microscope were conducted.Results:After 12 weeks of peritoneal injection, the weight of rats in HK group decreased and activity increased than the NS group, while the rats in MT group just the same as the rats in NS group. The HE staining shows that the bladder epitheliums of HK group are thinner than other groups and some even fall off in some cases. The bladder epitheliums of MT group just the same as the NS group, which means there is no significant epithelium fall off even edema in this two groups. The Masson staining shows that the fibers in HK group increased when comparing to NS group and there is no difference between NS group and MT group. The immunohistochemistry staining shows that iNOS and COX-2 protein are all increased relatively in HK group (P<0.05) when compared to the NS group, and they all decreased when compares the MT group to HK group (P<0.05).Furthermore, there is no significant difference between the MT group and the NS group. The result of TUNEL assay is that the HK group have higher numbers of apoptotic cells compared with NS group and MT group (P<0.05).The transmission electron microscope finds that the mitochondrial vacuolation and swelling in bladder epithelium of the HK group.Conclusion:Oxidative stress related enzymes, iNOS and COX-2 protein, may have an important role in ketamine abuse related bladder injury. Melatonin, a powerful antioxidant, can protect the bladder of the rats from ketamine abuse related bladder injury.