Sildenafil improves radiation-induced oral mucositis by attenuating oxidative stress, NF-κB, ERK and JNK signalling pathways
Abstract
Gastric ulcers, a prevalent gastrointestinal disorder marked by mucosal damage, sometimes resist complete healing with existing therapies. This study evaluated the therapeutic potential of tadalafil, both alone and in combination with omeprazole, in a rat model of acetic acid-induced chronic gastric ulcer. Male Wistar rats were divided into six groups: sham, model, omeprazole (40 mg/kg), low-dose tadalafil (20 mg/kg), high-dose tadalafil (40 mg/kg), and a combination of tadalafil (20 mg/kg) and omeprazole (40 mg/kg). Gastric ulcers were induced using acetic acid, followed by daily oral treatments for 12 days. Parameters assessed included ulcer size, lipid peroxidation, and the expression of nuclear factor kappa B (NF-κB, a protein complex regulating inflammation), vimentin, and proliferating cell nuclear antigen (PCNA, a marker of cell proliferation). Additionally, mRNA levels of AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), along with tissue nitric oxide (NO) metabolites (NOx), were measured. Low-dose tadalafil (20 mg/kg) significantly decreased ulcer size and inflammation while enhancing cell proliferation, independent of AMPK mRNA change. In contrast, high-dose tadalafil (40 mg/kg) failed to confer similar benefits, exacerbating inflammation and increasing NOx levels. The combination of tadalafil and omeprazole demonstrated efficacy comparable to low-dose tadalafil alone, sustaining eNOS…
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