Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effect of rosiglitazone on 20-hydroxyeicosatetraenoic acid levels and CYP4F2 expression in HepG2 cells

Yazun Jarrar^1,2, Su-Jun Lee¹

¹Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, Busan, South Korea; ²Department of Pharmacy, College of Pharmacy, Alzaytoonah University of Jordan, Amman, Jordan.

For correspondence:- Su-Jun Lee Email: 2sujun@inje.ac.kr Tel:+82518905911

Accepted: 18 March 2021 Published: 30 April 2021

Citation: Jarrar Y, Lee S. Effect of rosiglitazone on 20-hydroxyeicosatetraenoic acid levels and CYP4F2 expression in HepG2 cells. Trop J Pharm Res 2021; 20(4):703-708 doi: 10.4314/tjpr.v20i4.6

© 2021 The authors.
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Abstract

Purpose: To determine the effect of rosiglitazone on the levels of the cardiotoxic arachidonic acid metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE), in the human liver hepatocellular carcinoma cell line, HepG2.

Methods: HepG2 cells were treated with thiazolidinedione rosiglitazone and the mRNA and protein expressions of cytochrome P450 4F2 (CYP4F2) responsible for synthesizing 20-HETE were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The levels of 20-HETE were evaluated using liquid chromatography/mass spectrometry (LC-MS).

Results: Rosiglitazone significantly increased the levels of CYP4F2 mRNA and protein when compared with the control group (p < 0.05). This was correlated with significantly increased 20-HETE levels in the culture medium of rosiglitazone-treated cells in a dose-dependent manner (p < 0.05). The PPARγ antagonist, GW9662, significantly repressed the increased production of 20-HETE and CYP4F2 mRNA protein (p < 0.05).

Conclusion: Rosiglitazone increases the synthesis of 20-HETE via activation of PPARγ receptor and upregulation of CYP4F2. These findings may provide an additional explanation, at least in part, for the unwanted side effects of rosiglitazone on the cardiovascular system.

Keywords: Thiazolidinediones; 20-HETE, CYP4, PPAR?, HepG2 cells