Samaneh Nakhaee1, Mohammad Dastjerdi2, Hesam Roumi2, Omid Mehrpour1,3, Khadijeh Farrokhfall4. 1. Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS), Birjand, Iran. 2. Cardiovascular Research Center, Birjand University of Medical Sciences, Birjand, Iran. 3. Mel and Enid Zuckerman, College of Public Health, University of Arizona, Tucson, Arizona, USA. 4. Cardiovascular Research Center, Birjand University of Medical Sciences, Birjand, Iran. kfarrokhfall@yahoo.com.
Abstract
BACKGROUND: Acetaminophen (APAP) induced hepatotoxicity is a clinically important problem. Up to now, interventive therapy with n-acetylcysteine (NAC) has been considered as a gold-standard treatment for APAP overdose. However, no study has focused on the efficacy of these drugs' concurrent administration on probable enhancing therapeutic outcomes. Thus, this study was aimed to investigate the analgesic effect of co-administration of NAC and acetaminophen in male rats. The NAC-APAP drug formulation may demonstrate the stranger antinociceptive effect. METHODS: Forty-eight male Sprague-Dawley rats (12-14 weeks) randomly divided into six equal groups; control, APAP (received 300 mg/kg APAP), NAC (received 600 mg/kg NAC) and APAP+ NAC groups that received simultaneously 300 mg/kg APAP with 200-600 mg/kg NAC (AN200, AN400, AN600). All administrations were done orally for once. The antinociceptive effect was recorded by measurement of latency period on a hot plate in 30, 60, and 90 min after administrations. RESULTS: The results showed that NAC's concurrent administration with APAP, dose-dependently increased APAP analgesic effects (p< 0.0001). Moreover, NAC treatment exhibited an antinociceptive effect in 60 and 90 min, per se. The treatments had no adverse effect on liver enzymes and oxidative stress. CONCLUSION: Co-administration of NAC with APAP can improve the antinociceptive effect of APAP. It is suggested that this compound can enhance analgesic effects of APAP and eventually lead to a reduction in acetaminophen dose. Further studies are needed to evaluate the molecular mechanism of this hyper analgesic effect.
BACKGROUND: Acetaminophen (APAP) induced hepatotoxicity is a clinically important problem. Up to now, interventive therapy with n-acetylcysteine (NAC) has been considered as a gold-standard treatment for APAP overdose. However, no study has focused on the efficacy of these drugs' concurrent administration on probable enhancing therapeutic outcomes. Thus, this study was aimed to investigate the analgesic effect of co-administration of NAC and acetaminophen in male rats. The NAC-APAP drug formulation may demonstrate the stranger antinociceptive effect. METHODS: Forty-eight male Sprague-Dawley rats (12-14 weeks) randomly divided into six equal groups; control, APAP (received 300 mg/kg APAP), NAC (received 600 mg/kg NAC) and APAP+ NAC groups that received simultaneously 300 mg/kg APAP with 200-600 mg/kg NAC (AN200, AN400, AN600). All administrations were done orally for once. The antinociceptive effect was recorded by measurement of latency period on a hot plate in 30, 60, and 90 min after administrations. RESULTS: The results showed that NAC's concurrent administration with APAP, dose-dependently increased APAP analgesic effects (p< 0.0001). Moreover, NAC treatment exhibited an antinociceptive effect in 60 and 90 min, per se. The treatments had no adverse effect on liver enzymes and oxidative stress. CONCLUSION: Co-administration of NAC with APAP can improve the antinociceptive effect of APAP. It is suggested that this compound can enhance analgesic effects of APAP and eventually lead to a reduction in acetaminophen dose. Further studies are needed to evaluate the molecular mechanism of this hyper analgesic effect.
Entities:
Keywords:
Acetaminophen; Analgesic effect; Co-administration; Hot plate; N-acetyl cysteine; Pain; Rat
Authors: T Pelissier; A Alloui; F Caussade; C Dubray; A Cloarec; J Lavarenne; A Eschalier Journal: J Pharmacol Exp Ther Date: 1996-07 Impact factor: 4.030
Authors: Andréa Horst; Carolina Kolberg; Maira S Moraes; Ana Paula K Riffel; Isabela A Finamor; Adriane Belló-Klein; Maria Amália Pavanato; Wania A Partata Journal: Neurosci Lett Date: 2014-04-03 Impact factor: 3.046