AI Article Synopsis

  • Cytochrome P450 2E1 (CYP2E1) plays a key role in converting isoniazid (INH) into harmful metabolites, contributing to liver damage; this study examines the impact of folic acid (FA) on this process.
  • In a controlled experiment with male Balb/c mice, those receiving folic acid showed lower levels of the enzyme CYP2E1 and reduced liver injury indicators compared to those not receiving FA, suggesting a protective effect.
  • The findings indicate that folic acid may help alleviate INH-induced liver injury by decreasing CYP2E1 expression and enhancing certain metabolic pathways, particularly through increased RNA methylation levels.

Article Abstract

Background: Cytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury.

Methods: Male Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism.

Results: FA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The -methyladenosine RNA methylation level of significantly increased in the FA group compared with the INH group, while the DNA methylation levels of were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of .

Conclusion: FA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116731PMC
http://dx.doi.org/10.3389/fnut.2024.1389684DOI Listing

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