Evaluation of Therapeutic Effects of Vardenafil Targeting Nrf2 and NLRP3 Inflammasomes in a Rat Model of Ulcerative Colitis

Abstract

Aims: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disorder that known to increase the risk of colon cancer. Erectile dysfunction(ED) is common in patients with UC. Vardenafil, which is a drug commonly prescribed for treatment of ED, has been shown to have antioxidant effects; nevertheless, its significance in UC has not been determined. Thus, this current study was designed to investigate the potential therapeutic effects of vardenafil against acetic acid-induced UC and to identify possible underlying mechanisms.

Main methods: Induction of UC was accomplished using 3% acetic acid (AA) instilled rectally. In total, 45 male Wistar rats were classified into 5 groups: control group, UC group, sulfasalazine (100 mg\kg\day) group vardenafil (10 mg\kg\day) group, and combined sulfasalazine and vardenafil group.

Key findings: Vardenafil, alone and in combination with sulfasalazine, significantly ameliorated the severity of UC as indicated by reduced colon weight/body weight ratio, colon weight /colon length ratio, and macroscopic and microscopic scores of UC. Vardenafil significantly reduced oxidative stress as evidenced by decreased malondialdehyde abundance and increased colonic superoxide dismutase, nuclear factor erythroid-2-related factor-2, and heme oxygenase_1 concentrations. Moreover, treatment with vardenafil significantly suppressed NLRP3 inflammasome signaling pathway as indicated by decreased colonic concentrations of NOD-like receptor 3, caspase-1, and interleukin 1 beta.

Significance: Our findings prove that vardenafil has anti-inflammatory and anti-oxidant effects against AA-induced UC through activating Nrf2 signaling and suppressing NLRP3 inflammasome activation. Thus, vardenafil may represent a promising therapeutic candidate for treatment of UC especially for UC patients suffering from ED.

Aims: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disorder that known to increase the risk of colon cancer. Erectile dysfunction(ED) is common in patients with UC. Vardenafil, which is a drug commonly prescribed for treatment of ED, has been shown to have antioxidant effects; nevertheless, its significance in UC has not been determined. Thus, this current study was designed to investigate the potential therapeutic effects of vardenafil against acetic acid-induced UC and to identify possible underlying mechanisms.

Main methods: Induction of UC was accomplished using 3% acetic acid (AA) instilled rectally. In total, 45 male Wistar rats were classified into 5 groups: control group, UC group, sulfasalazine (100 mg\kg\day) group vardenafil (10 mg\kg\day) group, and combined sulfasalazine and vardenafil group.

Key findings: Vardenafil, alone and in combination with sulfasalazine, significantly ameliorated the severity of UC as indicated by reduced colon weight/body weight ratio, colon weight /colon length ratio, and macroscopic and microscopic scores of UC. Vardenafil significantly reduced oxidative stress as evidenced by decreased malondialdehyde abundance and increased colonic superoxide dismutase, nuclear factor erythroid-2-related factor-2, and heme oxygenase_1 concentrations. Moreover, treatment with vardenafil significantly suppressed NLRP3 inflammasome signaling pathway as indicated by decreased colonic concentrations of NOD-like receptor 3, caspase-1, and interleukin 1 beta.

Significance: Our findings prove that vardenafil has anti-inflammatory and anti-oxidant effects against AA-induced UC through activating Nrf2 signaling and suppressing NLRP3 inflammasome activation. Thus, vardenafil may represent a promising therapeutic candidate for treatment of UC especially for UC patients suffering from ED.