Role of ADMA/DDAH-1 and iNOS/eNOS signaling in the gastroprotective effect of tadalafil against indomethacin-induced gastric injury.

Autor: Mohamed YT; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 62514, Egypt. Electronic address: yasmin.ibrahim@nub.edu.eg., Naguib IA; Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia. Electronic address: i.abdelaal@tu.edu.sa., Abo-Saif AA; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 62514, Egypt. Electronic address: ali.aboseif@nub.edu.eg., Elkomy MH; Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia. Electronic address: mhalkomy@ju.edu.sa., Alghamdi BS; Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah 22252, Saudi Arabia; Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: basalghamdi@kau.edu.sa., Mohamed WR; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: wafaa.mohamed@pharm.bsu.edu.eg.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Jun; Vol. 150, pp. 113026. Date of Electronic Publication: 2022 Apr 28.
DOI: 10.1016/j.biopha.2022.113026
Abstrakt: Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcers represent a significant clinical concern and adversely affect the quality of life. Inducible nitric oxide synthase/endothelial nitric oxide synthase (iNOS/eNOS) and asymmetric dimethylarginine/ dimethylarginine dimethylaminohydrolase-1 (ADMA/DDAH-1) signaling are key players in gastric ulcer pathogenesis. This work was planned to explore the role of iNOS/eNOS and ADMA/DDAH-1 signaling in rats with indomethacin-induced gastric ulcer, as potential pathways for the gastro-protective effect of tadalafil. Split into 5 separate groups, rats were assigned to control, tadalafil (10 mg/kg, p.o), indomethacin (single oral dose of 60 mg/kg), indomethacin + pantoprazole (40 mg/kg, p.o), and indomethacin + tadalafil (10 mg/kg, p.o). The results indicated that pretreatment with tadalafil significantly reduced ulcer index (UI), increased preventive index (PI), and counteracted indomethacin-induced histopathological aberrations. Tadalafil significantly reduced the gastric content of NO while it significantly elevated that of GSH and enhanced SOD activity. It significantly reduced the gastric expression of TNF-α and ADMA while it significantly elevated that of COX-2, PGE-2, and DDAH-1. Western blot analysis revealed that pretreatment with tadalafil significantly reduced iNOS protein expression while it significantly elevated that of eNOS. Collectively, these data suggest that tadalafil exerts potential protective effect against indomethacin-induced ulcer through suppression of inflammation, attenuation of oxidative stress, and boosting of antioxidants. Moreover, tadalafil protective effects are mediated via upregulation of PGE-2 with modulating the signaling pathways of ADMA/DDAH-1, and iNOS/eNOS. As a result, the current evidence corroborates the use of tadalafil in controlling gastric ulcers and preventing NSAID gastric side effects.
(Copyright © 2022. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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