FEBS Open Bio (Apr 2023)

Effect of atorvastatin on lipoxygenase pathway‐related gene expression in an in vitro model of lipid accumulation in hepatocytes

  • Ivanna Carolina Golfetto Miskiewicz,
  • Hyen Chung Cho,
  • Ji In Lee,
  • Jihye Lee,
  • Yenna Lee,
  • Yun Kyung Lee,
  • Sung Hee Choi

DOI
https://doi.org/10.1002/2211-5463.13552
Journal volume & issue
Vol. 13, no. 4
pp. 606 – 616

Abstract

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Lipid accumulation in hepatocytes can result from an imbalance between lipid acquisition and lipid catabolism. In recent years, it has been discovered that eicosanoids derived from arachidonic acid (AA) have the potential to create specialized pro‐resolving lipid mediators to actively resolve inflammation, but it is not clear whether AA and lipoxygenases exert effects on hepatic inflammation. Here, the effects of atorvastatin on the expression of cytoplasmic phospholipase A2 (cPLA2) and lipoxygenase pathway genes (ALOX5, ALOX12, ALOX15, and ALOX15B) were evaluated in an in vitro model of palmitic acid (PA)‐induced hepatocyte lipid accumulation in McA‐RH7777 (McA) cells. Palmitic acid increased cPLA2 expression, intracellular AA levels, and ALOX12 expression (P < 0.05). Atorvastatin at various concentrations had no significant effects on AA levels or on cPLA2, ALOX15, and ALOX15B expressions. ALOX5 was not detected, despite multiple measurements. Pro‐inflammatory IL‐1β expression levels were upregulated by PA (P < 0.01) and attenuated by atorvastatin (P < 0.001). TNFα did not differ among groups. The expression levels of anti‐inflammatory IL‐10 decreased in response to PA (P < 0.05), but were not affected by atorvastatin. In conclusion, in an in vitro model of lipid accumulation in McA cells, atorvastatin reduced IL‐1β; however, its effect was not mediated by AA and the lipoxygenase pathway at the established doses and treatment duration. Further research is required to investigate time‐response data, as well as other drugs and integrated cell systems that could influence the lipoxygenase pathway and modulate inflammation in liver diseases.

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