Protective effects of guarana (Paullinia cupana) against methotrexate-induced intestinal damage in mice

Abstract

This study aimed to examine the effects of guarana ( Paullinia cupana ) on intestinal damage induced by MTX in mice. Mice were classified into four groups: control, MTX, guarana ( Paullinia cupana ), and guarana ( Paullinia cupana ) together with MTX. Total antioxidant capacity together with glutathione, superoxide dismutase, MDA, ALT, AST, myeloperoxidase, total protein and IL-1β were detected in the serum. Bax and Bcl2 expressions were detected in intestine together with histopathological examination and immunohistochemical examination of caspase-9. Intoxication with MTX inhibited antioxidant and promoted myeloperoxidase activity in experimental mouse models but pre-administration of guarana ameliorated this effect by inhibiting IL-1β. Real-time quantitative PCR (qRT-PCR) analysis found that MTX intoxication upregulated BAX expression, causing apoptosis, and downregulated Bcl2 expression. These were also brought under control following guarana pre-administration. Histological examination of intestine indicated hyperplasia and desquamation of superficial epithelium of villi in the MTX-administered group, as well as round cell infiltration in the lamina propria. Pre-administration of guarana protected against these effects. The MTX group showed that caspase-9 expression was upregulated, increasing immune-reactivity in comparison to the guarana experimental groups. These combined effects lead to the conclusion that guarana has a preventative or protective effect against MTX-induced oxidative stress in the intestinal tissue.