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Role of free radical scavenging activity of vasoactive intestinal peptide in the attenuation of mitochondrial dysfunction to ameliorate dextran sulphate sodium‐induced colitis in mice: Implications in ulcerative colitis
Author(s) -
Spoorthi Bengaluru Chandraiah,
More Sunil S.,
Gautham Santhekadur Annappa,
Ghosh Shashwati,
Saha Ishita,
Maiti Arpan Kumar
Publication year - 2020
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/1751-2980.12932
Subject(s) - vasoactive intestinal peptide , colitis , superoxide dismutase , nitric oxide , ulcerative colitis , chemistry , catalase , peroxynitrite , pharmacology , biochemistry , medicine , hydroxyl radical , nitric oxide synthase , superoxide , oxidative stress , antioxidant , enzyme , receptor , disease , neuropeptide
Objective To evaluate the efficacy of vasoactive intestinal peptide (VIP) in treating ulcerative colitis (UC), targeting colonic mitochondrial dysfunction by virtue of its free radical scavenging properties for maintenance of colon mucosal integrity. Methods A murine model was administered with dextran sodium sulfate (DSS) to induce colitis in C57BL/6J mice at 3.5%/g bodyweight for 3 cycles of 5 days each, followed by an intraperitoneal dose of VIP at 0.5 nmol/L per mouse per day for 10 days. The post‐treatment mice were sacrificed and their colon samples were utilized for further analysis. To substantiate the in vivo findings and identify the reactive species involved in progression of UC, Caco‐2 cells were subjected to DSS (5%) for 24 hours at 37 °C with or without VIP (10 nmol/L) in the presence or absence of specific free radical scavengers and antioxidants. Results Treatment with VIP reduced histopathological severity of colitis and cell death markers in murine model, leading to partial recovery of inhibited mitochondrial respiratory complexes, altered mitochondrial membrane potential and lowered adenosine triphosphate generation. Interestingly, in vitro treatment with VIP restored mitochondrial functions and its efficacy was equal to super oxide dismutase and dimethyl sulfoxide, indicating involvement of superoxide free radical (O 2 •‐ ) and hydroxyl radical ( • OH) in progression of UC. However, catalase, N ω ‐nitro‐ l ‐arginine methyl ester and mercaptoethylguanidine were ineffective, indicating non‐involvement of hydrogen peroxide, nitric oxide and ONOO − in UC. Conclusion By virtue of its free radical scavenging properties VIP can act as a potent anti‐colitogenic agent, reversing colonic mitochondrial dysfunction for treating UC.