Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

Abstract

Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

Nimesulide Inhibits MAPK/COX-2 Pathway, and Prevents Oxidative Stress, Inflammation, and Apoptosis in Testes of Cisplatin-Challenged Rats

“…The selective COX-2 inhibitor, NSE, exerted antioxidant, antinitrosative, anti-inflammatory, and anti-apoptotic properties in different models of tissue injuries, including the testes. Similar to the current study, prior investigations revealed that NSE reduced the production of oxidative/nitrosative stress biomarkers and inflammatory cytokines, preserved the endogenous antioxidants, and prevented the elevations of apoptotic biomarkers [8][9][10][11][12]. In addition, prior investigations demonstrated that oxidative stress induced by CSP up-regulated JNK and p38 MAPKs signaling pathways.…”

“…It is approved for the treatment of acute pains, osteoarthritis, and primary dysmenorrhea [7]. It was reported in the literature that NSE provided significant antioxidant, antiinflammatory, and anti-apoptotic effects in different models [8][9][10][11]. Additionally, a recent study showed that NSE significantly protected the testes of rats against ischemia/reperfusion injury resulting from torsion/detorsion [12].…”

Development of an alternative zebrafish model for drug‐induced intestinal toxicity

“…Indomethacin is a representative of intestinal toxicants that can cause lesions in the gastrointestinal tract by direct mucosal irritation and by inhibition of prostaglandin synthesis (Khazaeinia & Jamali, ). Diclofenac and methotrexate are also representative intestinal toxicants causing the ulcer, bleeding or inflammation of the small intestine (Arslan et al, ; Zhong et al, ). We compared zebrafish against rat and Caco‐2 cell line models as an alternative model for drug‐induced intestinal toxicity.…”

Effects of anakinra on the small intestine mucositis induced by methotrexate in rats

“…reactive oxygen species are known to have a role in the oxidative stress caused by MtX [11]. Arslan et al reported that MdA level which is the end product of lipid peroxidation was increased; tGsH, glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase which are antioxidants were decreased in the small intestine mucositis caused by MtX [3]. MtX caused oxidative stress by increasing MdA levels and decreasing tGsH levels in the small intestine tissue and confirmed histopatho-logical changes [2].…”