gene reduces oxidative stress in the bladder by regulating the NF-κB pathway in a mouse model of ketamine-induced cystitis.

Aldehyde dehydrogenase 2 (aldh2) serves an important role in the development of organ injury. Therefore, the present study investigated the effects of aldh2 on the oxidative stress response in a mouse model of ketamine-induced cystitis (KIC). A total of 60 8-week-old male Institute of Cancer Research wild-type (WT) mice and 45 knock-out (KO) mice were randomized to receive low-dose ketamine (30 mg/kg), high-dose ketamine (60 mg/kg) or normal saline (controls). At 4, 8 and 12 weeks post-injection, bladder tissues were harvested and used to investigate the protective mechanisms of aldh2 on bladder function. The results demonstrated that KO mice exhibited significant weight loss following chronic ketamine injection compared with that in WT mice. Furthermore, ketamine treatment increased the urination rate (P<0.05), pathological score (P<0.05), levels of the oxidative stress product malondialdehyde (P<0.05) in addition to reducing the expression of the anti-oxidative stress enzyme superoxide dismutase (P<0.05) and glutathione-SH (P<0.05). Oxidative stress in KO mice was also found to significantly enhance the expression of proteins associated with the NF-κB signaling pathway, which promoted the expression of inducible nitric oxide synthase (P<0.05) and cyclooxygenase-2 (P<0.05) further. Finally, KO mice demonstrated higher severity of fibrosis in the submucosal and muscular layers of the bladder. In conclusion, the present study suggests that aldh2 serves a protective role in preventing inflammation and fibrosis in KIC.