Amelioration of adrenaline induced oxidative gastrointestinal damages in rat by melatonin through SIRT1-NFκB and PGC1α-AMPKα cascades

Melatonin prevents adrenaline induced intestinal damage

  • Palash Kumar Pal Department of Physiology, University of Calcutta, Rajabazar Science College Campus, 92, APC Road, Kolkata 700 009, INDIA
  • Swaimanti Sarkar Department of Physiology, University of Calcutta, Rajabazar Science College Campus, 92, APC Road, Kolkata 700 009, INDIA
  • Sanatan Mishra Department of Physiology, Vidyasagar College, Kolkata 700 006, INDIA
  • Sreya Chattopadhyay Department of Physiology, University of Calcutta, Rajabazar Science College Campus, 92, APC Road, Kolkata 700 009, INDIA
  • Aindrila Chattopadhyay Department of Physiology, Vidyasagar College, Kolkata 700 006, INDIA
  • Debasish Bandyopadhyay aOxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University of Calcutta, 92, APC Road, Kolkata-700009
Keywords: adrenaline, oxidative stress, tissue damage, antioxidant, gastrointestinal tract, melatonin

Abstract


Adrenaline at high pharmacological doses may lead to oxidative damages in diverse organs including gut. In this study, we attempt to elucidate the potentially protective effects of melatonin on gastrointestinal (GI) tissue damages induced by adrenaline. Rats were injected (s.c.) with different doses (0.125, 0.25 and 0.50 mg/kg) of adrenaline bitartrate (AD) for 15 days with or without melatonin (2.5, 5 and 10 mg/kg; orally). The results showed that adrenaline caused massive histological and ultra-structural GI injuries and melatonin (20 mg/kg) effectively protected these injuries. The protective mechanisms are related to the antioxidant and anti-inflammatory activities of melatonin indicated by increased glutathione levels and antioxidant enzymes as well as decreased oxidative stress markers and pro-inflammatory cytokines in GI tissues. The signal pathways of melatonin include up-regulating expression of Nrf2, SIRT1 and Bcl2, while down-regulating NFκB, TNFα and Bax. Melatonin also targeted mitochondrial energy homeostasis and biogenesis by up-regulating expression of PGC1α, AMPKα and SOD2 and reduced leakage of cytochrome c.  The SIRT1-NFκB and PGC1α-AMPKα signal transduction pathways seem to play the central roles involving in melatonin’s protective effects on gastric damages induced by the high doses of adrenaline.


 

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Published
2020-10-09
How to Cite
[1]
Pal, P.K., Sarkar, S., Mishra, S., Chattopadhyay, S., Chattopadhyay, A. and Bandyopadhyay, D. 2020. Amelioration of adrenaline induced oxidative gastrointestinal damages in rat by melatonin through SIRT1-NFκB and PGC1α-AMPKα cascades. Melatonin Research. 3, 4 (Oct. 2020), 482-502. DOI:https://doi.org/https://doi.org/10.32794/mr11250074.
Section
Research Articles

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