Protective effect of NAC against malathion-induced oxidative stress in freshly isolated rat hepatocytes
Journal Title: Advanced Pharmaceutical Bulletin - Year 2012, Vol 2, Issue 1
Abstract
Purpose: Induction of oxidative stress by Organophosphate compounds (OPs) has been previously reported. In the present work, the mechanism of protective effects of N-acetylcysteine as a glutathion (GSH) prodrug against malathion–induced cell toxicity was investigated. In this work, freshly isolated rat hepatocytes were used to determine the effect of NAC on malathion-induced cytotoxicity, formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Methods: Rat hepatocytes were isolated using collagenase perfusion and then cell viability, mitchondrial membrane potential (MMP) and ROS formation were determined using trypan blue exclusion, Rhodamine 123 fluorescence and fluorogenic probe, 2', 7' -dichlorofluorescin diacetate (DCFH-DA), respectively. Results: Despite the protective effect of NAC on malathion-induced cell toxicity and MMP dysfunction, its efficacy against ROS formation was not adequate to completely protect the cells. Conclusion: Cytotoxic effects of malathion regardless of its cholinergic feature, is started with gradual free radical production but, the main factor that causes cell death, is mitochondrial dysfunction, so that reduction of ROS formation alone is not sufficient for cell survival, and the maintenance of mitochondrial integrity through different mechanisms is the most ameliorative factor specially at high levels of cell damage, as NAC seemed to protect cells with various fashions apart from ROS scavenging in concentrations higher than malathion’s LC50.
Authors and Affiliations
Sara Mostafalou, Mohammad Abdollahi, Mohammad Ali Eghbal, Nazli Saeedi Kouzehkonani
Keywords
Related Articles
- EP ID EP114562
- DOI 10.5681/apb.2012.011
- Views 108
- Downloads 0
Effect of Aflatoxin B1 on Growth of Bovine Mammary Epithelial Cells in 3D and Monolayer Culture System
Purpose: Many studies have been showed transfer of aflatoxins, toxins produced by Aspergillus flvaus and Aspergillus parasiticus fungi, into milk. These toxins are transferred into the milk through digestive system by ea...
Comparison of Cytotoxic Activity of L778123 as a Farnesyltranferase Inhibitor and Doxorubicin against A549 and HT-29 Cell Lines
Purpose: Farnesyltransferase (FTase) is a zinc-dependent enzyme that adds a farnesyl group to the Ras proteins. L778, 123 is a potent peptidomimetic imidazole-containing FTase inhibitor. Methods: L778123 was synthesized...
Antimicrobial and Cytotoxic Activity of Three Bitter Plants-Enhydra fluctuans, Andrographis Peniculata and Clerodendrum Viscosum.
Purpose: In this study, three important medicinal plants (Enhydra fluctuans Lour, Clerodendrum viscosum Vent and Andrographis peniculata Wall) of Bangladesh were investigated to analyze their antimicrobial and cytotoxic...
Cytoprotective Effects of Organosulfur Compounds against Methimazole-Induced Toxicity in Isolated Rat Hepatocytes
Purpose: Methimazole is a drug widely used in hyperthyroidism. However, life-threatening hepatotoxicity has been associated with its clinical use. No protective agent has been found to be effective against methimazole-in...
Lactose Engineering for Better Performance in Dry Powder Inhalers
Dry powder inhaler (DPI) is generally formulated as a powder mixture of coarse carrier particles and micronized drug with aerodynamic diameters of 1-5 μm. Carrier particles are used to improve drug particle flowability,...