期刊
INFLAMMOPHARMACOLOGY
卷 31, 期 4, 页码 2091-2102出版社
SPRINGER BASEL AG
DOI: 10.1007/s10787-023-01261-6
关键词
Intestinal toxicity; Chemotherapy; Mitochondrial oxidative stress; Mitochondrial dysfunction; Mitochondria-targeted antioxidant; Combinatorial therapy
This study investigated the protective effect of Mito-TEMPO against 5-FU-induced intestinal toxicity. The results showed that Mito-TEMPO pre-treatment improved intestinal histopathological alterations, reduced inflammatory cell infiltration and apoptotic cell death, and improved mitochondrial function and oxidative stress. Therefore, Mito-TEMPO may be used as an adjuvant therapy in 5-FU chemotherapy.
BackgroundRecent evidences highlight role of mitochondria in the development of 5-fluorouracil (5-FU)-induced intestinal toxicity. Mitochondria-targeted antioxidants are well-known for their protective effects in mitochondrial oxidative stress- mediated diseases. In the present study, we investigated protective effect of Mito-TEMPO in 5-FU-induced intestinal toxicity.MethodsMito-TEMPO (0.1 mg/kg b.w.) was administered intraperitoneally to male BALB/c mice for 7 days, followed by co-administration of 5-FU for next 4 days (intraperitoneal 12 mg/kg b.w.). Protective effect of Mito-TEMPO on intestinal toxicity was assessed in terms of histopathological alterations, modulation in inflammatory markers, apoptotic cell death, expression of 8-OhDG, mitochondrial functional status and oxidative stress.Results5-FU administered animals showed altered intestinal histoarchitecture wherein a shortening and atrophy of the villi was observed. The crypts were disorganized and inflammatory cell infiltration was noted. Mito-TEMPO pre-protected animals demonstrated improved histoarchitecture with normalization of villus height, better organized crypts and reduced inflammatory cell infiltration. The inflammatory markers and myeloperoxidase activity were normalized in mito-TEMPO protected group. A significant reduction in intestinal apoptotic cell death and expression of 8-OhDG was also observed in mito-TEMPO group as compared to 5-FU group. Further, mtROS, mtLPO and mitochondrial antioxidant defense status were improved by mito-TEMPO.ConclusionMito-TEMPO exerted significant protective effect against 5-FU-induced intestinal toxicity. Therefore, it may be used as an adjuvant in 5-FU chemotherapy.
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