Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study

• Published in: Inflammopharmacology 2023-08, Vol.31 (4), p.2091-2102
• Main Authors: Tambe, Prasad Kisan, Qsee, H. S., Bharati, Sanjay
• Format: Article
• Language: English
• Subjects: Allergology; Animals; Antioxidants - metabolism; Apoptosis; Biomedical and Life Sciences; Biomedicine; Dermatology; Gastroenterology; Immunology; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Male; Mice; Mitochondria; Mitomycin - metabolism; Mitomycin - pharmacology; Mitomycin - therapeutic use; Original; Original Article; Oxidative Stress; Pharmacology/Toxicology; Rheumatology
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-023-01261-6

Background Recent 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. Methods Mito-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. Results 5-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. Conclusion Mito-TEMPO exerted significant protective effect against 5-FU-induced intestinal toxicity. Therefore, it may be used as an adjuvant in 5-FU chemotherapy.