Protective Effect of Piperine on Indomethacin‐Induced Intestinal Damage

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammation and chronic pain. Chronic use of NSAIDs is associated with adverse events and organ damage, especially to the gastric mucosa and small intestine. This study evaluates the protective effect of piperine on indomethacin-induced intestinal damage. Eighteen male Mus musculus mice, aged 6-8 weeks, were used. Intestinal damage was induced with indomethacin (10 mg/mL) and cotreatment with piperine (20 mg/mL), both administered orally. After 14 days, the animals were euthanized. Biochemical serological analysis was performed. Intestinal inflammation was assessed based on macroscopic, histopathological, and metagenomic analyses. Histopathological analysis showed a reduction in small intestine inflammation (p < 0.05) and the disappearance of necrosis in the intestinal wall of the large intestine. Crypt and villus measurements showed increased values in the piperine-treated group (p < 0.05). An approximately six-fold increase in aspartate aminotransferase (AST) was observed in the Indomethacin group (p < 0.05). Regarding the intestinal microbiota, an increase in genus diversity was observed in the piperine-treated group (p < 0.05). There was a 50% reduction in micronucleus formation with the administration of piperine 20 mg/kg (p < 0.05). It was concluded that cotreatment with piperine has great potential in mitigating the side effects caused by NSAIDs.