<em>Aldh2</em> gene reduces oxidative stress in the bladder by regulating the NF‑&kappa;B pathway in a mouse model of ketamine‑induced cystitis

Abstract

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 aldh2 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 aldh2 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 aldh2 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, aldh2 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.

Aldehyde dehydrogenase 2 alleviates monosodium iodoacetate-induced oxidative stress, inflammation and apoptosis in chondrocytes via inhibiting aquaporin 4 expression

“…Clinically, abnormal ALDH2 expression contributes to a large amount of human diseases [ 27 , 28 ]. It has been reported that ALDH2 knock-out mice exhibits significantly enhanced oxidative stress and inflammation in ketamine-induced cystitis [ 7 ]. Activation of ALDH2 protects against fibrosis, apoptosis and necroptosis in primary cardiomyocytes induced by high glucose via repression of oxidative stress and inflammation [ 29 ].…”

“…Aldehyde dehydrogenase 2 (ALDH2), a member of the aldehyde dehydrogenase (ALDH) superfamily that has 19 ALDH subtypes, regulates aldehyde metabolism by eliminating cytotoxic aldehydes, thereby reducing oxidative stress and inhibiting the production of reactive oxygen species (ROS)-related toxic products [ 6 ]. Compelling evidence indicate that ALDH2 gene alleviates ketamine-induced cystitis in mouse model through inhibiting oxidative stress [ 7 ]. ALDH2 overexpression contributes to the reduction of ROS production and inhibit inflammation in high glucose-induced H9C2 cardiac cell injury [ 8 ].…”

A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma

“…Recently, intense efforts are being made to clarify the genome‐wide association of BUC and identify more valuable candidate genes for diagnostic markers, and therapeutic targets [ 5 ]. The variants of aldehyde dehydrogenase (ALDH2) enzyme were demonstrated to be closely associated with the higher recurrence rate of BUC [ 8 ]. CD44 polymorphisms probably responding for the susceptibility of BUC were potential for a molecular prognostic marker [ 9 ].…”