Drug Res (Stuttg) 2017; 67(04): 217-222
DOI: 10.1055/s-0042-123034
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Mechanistic Approach for Toxic Effects of Bupropion in Primary Rat Hepatocytes

Elham Ahmadian
1   Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2   Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3   Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
4   Students’ Research Committee, Tabriz University
,
Hossein Babaei
2   Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3   Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
Alireza Mohajjel Nayebi
3   Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
Aziz Eftekhari
3   Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
4   Students’ Research Committee, Tabriz University
,
Mohammad Ali Eghbal
2   Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3   Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 02 November 2016

accepted 21 November 2016

Publication Date:
24 January 2017 (online)

Abstract

Bupropion is a widely prescribed antidepressant/smoke cessation drug. However, hepatotoxicity is one of its side effects reported in some recipients. The mechanisms by which bupropion induces hepatotoxicity is not clear yet. This experiment was intended to assess the cytotoxic mechanisms of bupropion toward primary rat hepatocytes. Additionally, the effect of α-tocopherol succinate (ALPHA-TOS) and N-acetyl cysteine (NAC) and mitochondrial permeability transition (MPT) pore sealing agent cyclosporine A (Cs A) on this toxicity was investigated. Cell death, LDH leakage, reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and mitochondrial depolarization were examined as toxicity indicators. Results revealed that bupropion led to a surge in ROS formation, depletion of intracellular glutathione, elevation of LPO, and mitochondrial collapse. ALPHA-TOS, NAC and Cs A administration diminished the intensity of cellular damage caused by bupropion. This experiment suggests the protective role of ALPHA-TOS, NAC and Cs A against bupropion-mediated cytotoxicity possibly through their reactive radical scavenging properties and their impacts on mitochondria. Furthermore, mitochondria might be contributed to the oxidative stress response and subsequent toxicological results observed by bupropion.

 
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