Abstract
As controversy exists about the efficacy of substance P (SP) in treating ulcerative colitis (UC) with no previous study highlighting the impact of SP on mitochondrial dysfunction in this diseased condition, it became logical to perform the present study. C57BL/6 J mice were administered with DSS @ 3.5%/gm body weight for 3 cycles of 5 days each followed by i.v. dose of SP @ 5nmole per kg for consecutive 7 days. Histopathological features were noticed in the affected colon along with colonic mitochondrial dysfunction, alterations in mitochondrial stress variables and enhanced colonic cell death. Interestingly, SP failed to reverse colitic features and proved ineffective in inhibiting mitochondrial dysfunction. Unexpectedly SP alone seemed to impart detrimental effects on some of the mitochondrial functions, enhanced lipid peroxidation and increased staining intensities for caspases 3 and 9 in the normal colon. To substantiate in vivo findings and to assess free radical scavenging property of SP, Caco-2 cells were exposed to DSS with or without SP in the presence and absence of specific free radical scavengers and antioxidants. Interestingly, in vitro treatment with SP failed to restore mitochondrial functions and its efficacy proved below par compared to SOD and DMSO indicating involvement of O2•− and •OH in the progression of UC. Besides, catalase, L-NAME and MEG proved ineffective indicating non-involvement of H2O2, NO and ONOO− in UC. Thus, SP may not be a potent anti-colitogenic agent targeting colonic mitochondrial dysfunction for maintenance of colon epithelial tract as it lacks free radical scavenging property.
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Acknowledgements
The authors are thankful to the Department of Science and Technology (DST), New Delhi, India, for funding this research (Sanctioned No. EMR/SERB/2016/001981).
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Department of Science and Technology (DST), New Delhi, India (Grant No. EMR/SERB/2016/001981).
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Spoorthi B. C. (S.B.C); Shashwati Ghosh (S.G); Ishita Saha (I.S); Sunil S More (S.S.M); Gautham S.A (G.S.A); Arpan K Maiti (A.K.M). S.B.C, S.G, I.S, S.S.M and A.K.M were involved in bench work and performed the experiments. S.B.C, G.S.A, S.S.M and A.K.M designed the work and involved in conceptualization. All authors supported technically. A.K.M provided financial assistance. S.B.C, S.S.M and A.K.M interpreted data and wrote the manuscript, and all authors reviewed it.
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All experimental protocols were permitted by the ethical committee of animal care and use of Dayananda Sagar University, Bengaluru, Karnataka, India (Registration No. 606/02/C/CPCSEA).
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Chandraiah, S.B., Ghosh, S., Saha, I. et al. Substance P failed to reverse dextran sulfate sodium-induced murine colitis mediated by mitochondrial dysfunction: implications in ulcerative colitis. 3 Biotech 11, 199 (2021). https://doi.org/10.1007/s13205-021-02755-2
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DOI: https://doi.org/10.1007/s13205-021-02755-2