Effect of methylsulfonylmethane on oxidative stress and CYP3A93 expression in fetal horse liver cells
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Objective: Stress-induced cytotoxicity caused by xenobiotics and endogenous metabolites induces the production of reactive oxygen species and often results in damage to cellular components such as DNA, proteins, and lipids. The cytochrome P450 (CYP) family of enzymes are most abundant in hepatocytes, where they play key roles in regulating cellular stress responses. We aimed to determine the effects of the antioxidant compound, methylsulfonylmethane (MSM), on oxidative stress response, and study the cytochrome P450 family 3 subfamily A (<i>CYP3A</i>) gene expression in fetal horse hepatocytes.Methods: The expression of hepatocyte markers and <i>CYP3A</i> family genes (<i>CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96</i>, and <i>CYP3A97</i>) were assessed in different organ tissues of the horse and fetal horse liver-derived cells (FHLCs) using quantitative reverse transcription polymerase chain reaction. To elucidate the antioxidant effects of MSM on FHLCs, cell viability, levels of oxidative markers, and gene expression of <i>CYP3A</i> were investigated in H<sub>2</sub>O<sub>2</sub>-induced oxidative stress in the presence and absence of MSM.Results: FHLCs exhibited features of liver cells and simultaneously maintained the typical genetic characteristics of normal liver tissue; however, the expression profiles of some liver markers and <i>CYP3A</i> genes, except that of <i>CYP3A93</i>, were different. The expression of <i>CYP3A93</i> specifically increased after the addition of H<sub>2</sub>O<sub>2</sub> to the culture medium. MSM treatment reduced oxidative stress as well as the expression of <i>CYP3A93</i> and heme oxygenase 1, an oxidative marker in FHLCs.Conclusion: MSM could reduce oxidative stress and hepatotoxicity in FHLCs by altering <i>CYP3A93</i> expression and related signaling pathways.
Abstract
Objective: Stress-induced cytotoxicity caused by xenobiotics and endogenous metabolites induces the production of reactive oxygen species and often results in damage to cellular components such as DNA, proteins, and lipids. The cytochrome P450 (CYP) family of enzymes are most abundant in hepatocytes, where they play key roles in regulating cellular stress responses. We aimed to determine the effects of the antioxidant compound, methylsulfonylmethane (MSM), on oxidative stress response, and study the cytochrome P450 family 3 subfamily A (CYP3A) gene expression in fetal horse hepatocytes. Methods: The expression of hepatocyte markers and CYP3A family genes (CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, and CYP3A97) were assessed in different organ tissues of the horse and fetal horse liver-derived cells (FHLCs) using quantitative reverse transcription polymerase chain reaction. To elucidate the antioxidant effects of MSM on FHLCs, cell viability, levels of oxidative markers, and gene expression of CYP3A were investigated in H2O2-induced oxidative stress in the presence and absence of MSM. Results: FHLCs exhibited features of liver cells and simultaneously maintained the typical genetic characteristics of normal liver tissue; however, the expression profiles of some liver markers and CYP3A genes, except that of CYP3A93, were different. The expression of CYP3A93 specifically increased after the addition of H2O2 to the culture medium. MSM treatment reduced oxidative stress as well as the expression of CYP3A93 and heme oxygenase 1, an oxidative marker in FHLCs. Conclusion: MSM could reduce oxidative stress and hepatotoxicity in FHLCs by altering CYP3A93 expression and related signaling pathways.
참고문헌 (25)
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