Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression

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Nikravesh Hojatolla; KHODAYAR MOHAMMAD JAVAD; MAHDAVINIA MASOUD; MANSOURI ESRAFIL; Zeidooni Leila; DEHBASHI FERESHTEH

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Journal: Advanced Pharmaceutical Bulletin Year:2018 | Volume:8 | Issue:2 Page(s): 331-339

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Title

Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression

Author(s)

Keywords

Acetaminophen

Oxidative Stress

Gemfibrozil

Hepatoprotective

Mice

Abstract

Purpose: Gemfibrozil (GEM) apart from agonist activity at peroxisome proliferator-activated receptor-alpha (PPAR-α ) has antioxidant and anti-inflammatory properties. Accordingly, the present study was designed to investigate the protective effect of GEM on acute liver toxicity induced by Acetaminophen (APAP) in Mice. Methods: In this study, Mice divided in seven groups include, control group, APAP group, GEM group, three APAP groups pretreated with GEM at the doses of 25, 50 and 100 mg/kg respectively and APAP group pretreated with N-Acetyl cysteine. GEM, NAC or vehicle were administered for 10 days. In last day, GEM and NAC were gavaged 1 h before and 1 h after APAP injection. Twenty four hours after APAP, Mice were sacrificed. Serum parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver tissue markers including catalase enzyme activity, reactive oxygen species (ROS), malondialdehyde and reduced glutathione (GSH) levels determined and histopathological parameters measured. Results: GEM led to significant decrease in serum ALT and AST activities and increase in catalase activity and hepatic GSH level and reduces malondialdehyde and ROS levels in the liver tissue. In confirmation, histopathological findings revealed that GEM decrease degeneration, vacuolation and necrosis of hepatocytes and infiltration of inflammatory cells. Conclusion: Present data demonstrated that GEM has antioxidant properties and can protect the liver from APAP toxicity, just in the same pathway that toxicity occurs by toxic ROS and that GEM may be an alternative therapeutic agent to NAC in APAP toxicity.

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APA: Copy

Nikravesh, Hojatolla, KHODAYAR, MOHAMMAD JAVAD, MAHDAVINIA, MASOUD, MANSOURI, ESRAFIL, Zeidooni, Leila, & DEHBASHI, FERESHTEH. (2018). Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression. ADVANCED PHARMACEUTICAL BULLETIN, 8(2), 331-339. SID. https://sid.ir/paper/745772/en

Vancouver: Copy

Nikravesh Hojatolla, KHODAYAR MOHAMMAD JAVAD, MAHDAVINIA MASOUD, MANSOURI ESRAFIL, Zeidooni Leila, DEHBASHI FERESHTEH. Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression. ADVANCED PHARMACEUTICAL BULLETIN[Internet]. 2018;8(2):331-339. Available from: https://sid.ir/paper/745772/en

IEEE: Copy

Hojatolla Nikravesh, MOHAMMAD JAVAD KHODAYAR, MASOUD MAHDAVINIA, ESRAFIL MANSOURI, Leila Zeidooni, and FERESHTEH DEHBASHI, “Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression,” ADVANCED PHARMACEUTICAL BULLETIN, vol. 8, no. 2, pp. 331–339, 2018, [Online]. Available: https://sid.ir/paper/745772/en

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