Captopril suppresses hepatic mammalian target of rapamycin cell signaling and biomarkers of inflammation and oxidative stress in thioacetamide-induced hepatotoxicity in rats

Arch Physiol Biochem. 2021 Oct;127(5):414-421. doi: 10.1080/13813455.2019.1647249. Epub 2019 Jul 31.

Abstract

Background: The potential inhibitory effects of captopril, the angiotensin-converting enzyme inhibitor, on thioacetamide (TAA)-induced hepatic mammalian target of rapamycin (mTOR), liver injury enzymes, blood pressure, and biomarkers of inflammation and oxidative stress have not been investigated before.

Materials and methods: Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (model group) or were pretreated with captopril (150 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment (protective group).

Results: Captopril significantly (p < .05) inhibited TAA-induced hypertension, liver tissue levels of mTOR, TIMP-1, TNF-α, IL-6, MDA; and blood levels of lipids, ALT, and AST. We further demonstrated a significant (p < .01) positive correlation between mTOR scoring and the levels of inflammatory, oxidative and liver injury biomarkers.

Conclusions: Captopril protects against TAA-induced mTOR, liver injury enzymes, dyslipidemia, hypertension, inflammation, and oxidative stress.

Keywords: Captopril; liver injury; mTOR; rat model; thioacetamide.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Biomarkers* / metabolism
  • Captopril* / pharmacology
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Oxidative Stress* / drug effects
  • Rats
  • Rats, Wistar
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases* / metabolism
  • Thioacetamide* / toxicity

Substances

  • Captopril
  • Thioacetamide
  • TOR Serine-Threonine Kinases
  • Biomarkers
  • mTOR protein, rat
  • Angiotensin-Converting Enzyme Inhibitors