Effect of S-methylisothiourea in acetaminophen-induced hepatotoxicity in rat

Amar S. More, Rashmi R. Kumari, Gaurav Gupta, Kandasamy Kathirvel, Milindmitra K. Lonare, Rohini S. Dhayagude, Dhirendra Kumar, Dinesh Kumar, Anil K. Sharma, Surendra K. Tandan

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Nitric oxide synthesized from inducible nitric oxide synthase (iNOS) plays role in acetaminophen (APAP)-induced liver damage. The present study was undertaken to evaluate the effect of iNOS inhibitor S-methylisothiourea (SMT) in APAP-induced hepatotoxicity in rats (1 g/kg, i.p.). SMT was (10, 30, and 100 mg/kg; i.p.) given 30 min before and 3 h after APAP administration. At 6 and 24 h, blood was collected to measure alanine transaminase (ALT), aspartate transaminase (AST), and nitrate plus nitrite (NOx) levels in serum. At 48 h, animals were sacrificed, and blood and liver tissues were collected for biochemical estimation. SMT reduced significantly the serum ALT, AST, and NOx levels at 24 and 48 h and liver NOx levels at 48 h as compared with APAP-treated control. The amount of peroxynitrite measured by rhodamine assay was significantly reduced by SMT, as compared with APAP-treated control group. SMT treatment (30 mg/kg) has significantly reduced the lipid peroxidation and protein carbonyl levels, increased SOD and catalase, and reduced glutathione and total thiol levels significantly as compared with APAP-treated control. SMT 30 mg/kg dose has protected animals from APAP-induced hypotension and reduced iNOS gene expression. Hepatocytes were isolated from animals, and effect of SMT on apoptosis, MTP, and ROS generation was studied, and their increased value in APAP intoxicated group was found to be significantly decreased by SMT (30 mg/kg) at 24 and 48 h. In conclusion, nitric oxide produced from iNOS plays important role in toxicity at late hours (24 to 48 h), and SMT inhibits iNOS and reduces oxidative and nitrosative stress.

Original languageEnglish (US)
Pages (from-to)1127-1139
Number of pages13
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume385
Issue number11
DOIs
StatePublished - Nov 1 2012

Keywords

  • Acetaminophen
  • Inducible nitric oxide synthase (iNOS)
  • Peroxynitrite
  • Reactive oxygen species
  • S-methylisothiourea

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    More, A. S., Kumari, R. R., Gupta, G., Kathirvel, K., Lonare, M. K., Dhayagude, R. S., Kumar, D., Kumar, D., Sharma, A. K., & Tandan, S. K. (2012). Effect of S-methylisothiourea in acetaminophen-induced hepatotoxicity in rat. Naunyn-Schmiedeberg's Archives of Pharmacology, 385(11), 1127-1139. https://doi.org/10.1007/s00210-012-0789-0