Acetaminophen increases the risk of arsenic-mediated development of hepatic damage in rats by enhancing redox-signaling mechanism

Chhaya Rani Majhi, Saleem Khan, Marie Dennis Leo, Shahid Prawez, Amit Kumar, Palanisamy Sankar, Avinash Gopal Telang, Souvendra Nath Sarkar

Research output: Contribution to journalArticle

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Abstract

We evaluated whether the commonly used analgesic-antipyretic drug acetaminophen can modify the arsenic-induced hepatic oxidative stress and also whether withdrawal of acetaminophen administration during the course of long-term arsenic exposure can increase susceptibility of liver to arsenic toxicity. Acetaminophen was co-administered orally to rats for 3 days following 28 days of arsenic pre-exposure (Phase-I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase-II). Arsenic increased lipid peroxidation and reactive oxygen species (ROS) generation, depleted glutathione (GSH), and decreased superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR) activities. Acetaminophen caused exacerbation of arsenic-mediated lipid peroxidation and ROS generation and further enhancement of serum alanine aminotransferase and aspartate aminotransferase activities. In Phase-I, acetaminophen caused further GSH depletion and reduction in SOD, catalase, GPx and GR activities, but in Phase-II, only GPx and GR activities were more affected. Arsenic did not alter basal and inducible nitric oxide synthase (iNOS)-mediated NO production, but decreased constitutive NOS (cNOS)-mediated NO release. Arsenic reduced expression of endothelial NOS (eNOS) and iNOS genes. Acetaminophen up-regulated eNOS and iNOS expression and NO production in Phase-I, but reversed these effects in Phase-II. Results reveal that acetaminophen increased the risk of arsenic-mediated hepatic oxidative damage. Withdrawal of acetaminophen administration also increased susceptibility of liver to hepatotoxicity. Both ROS and NO appeared to mediate lipid peroxidation in Phase-I, whereas only ROS appeared responsible for peroxidative damage in Phase-II.

Original languageEnglish (US)
Pages (from-to)187-198
Number of pages12
JournalEnvironmental Toxicology
Volume29
Issue number2
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Fingerprint

Arsenic
Acetaminophen
Oxidation-Reduction
Rats
arsenic
damage
Liver
Glutathione Reductase
Reactive Oxygen Species
Nitric Oxide Synthase Type II
nitric oxide
Glutathione Peroxidase
Lipid Peroxidation
Nitric Oxide Synthase Type III
lipid
Lipids
Catalase
Superoxide Dismutase
Antipyretics
Oxidative stress

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

Cite this

Acetaminophen increases the risk of arsenic-mediated development of hepatic damage in rats by enhancing redox-signaling mechanism. / Majhi, Chhaya Rani; Khan, Saleem; Leo, Marie Dennis; Prawez, Shahid; Kumar, Amit; Sankar, Palanisamy; Telang, Avinash Gopal; Sarkar, Souvendra Nath.

In: Environmental Toxicology, Vol. 29, No. 2, 01.02.2014, p. 187-198.

Research output: Contribution to journalArticle

Majhi, Chhaya Rani ; Khan, Saleem ; Leo, Marie Dennis ; Prawez, Shahid ; Kumar, Amit ; Sankar, Palanisamy ; Telang, Avinash Gopal ; Sarkar, Souvendra Nath. / Acetaminophen increases the risk of arsenic-mediated development of hepatic damage in rats by enhancing redox-signaling mechanism. In: Environmental Toxicology. 2014 ; Vol. 29, No. 2. pp. 187-198.
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AU - Sarkar, Souvendra Nath

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