Cyp4f16, a member of the cytochrome P450 4F family, catalyzes the hydroxylation of eicosanoids such as leukotriene B(4), prostaglandins, lipoxins, and hydroxyeicosatetraenoic acids [2]. It is involved in the arachidonic acid metabolism pathway and its functions are likely tissue-and species-specific [2]. Genetic models like mouse models are valuable for studying its role.

In C57BL/6 mice, arsenic trioxide (ATO) treatment induced Cyp4f16, leading to a significant elevation in 20-HETE formation, indicating its role in ATO-induced alteration of hepatic arachidonic acid metabolite formation [1]. In HL-1 cells (a murine atrial cell line), Cyp4f16 mRNA levels were higher compared to mouse hearts, and the cells were able to metabolize arachidonic acid, suggesting a potential role in cardiovascular-related processes [3]. Also, acute mercury toxicity in C57Bl/6 mouse hearts induced Cyp4f16 gene expression, along with changes in other cytochrome P450s and soluble epoxide hydrolase, potentially contributing to mercury-induced cardiotoxicity [4].

In conclusion, Cyp4f16 is an important enzyme in the arachidonic acid metabolism pathway. Studies using mouse models, such as those exposed to ATO or mercury, have revealed its role in hepatic and cardiac processes related to these toxicant-induced responses. Understanding Cyp4f16's functions may provide insights into the mechanisms of hepatotoxicity and cardiotoxicity, offering potential targets for therapeutic intervention in related disease conditions.

References:

1. El-Ghiaty, Mahmoud A, Alqahtani, Mohammed A, El-Mahrouk, Sara R, Alammari, Ahmad H, El-Kadi, Ayman O S. 2024. Alteration of Hepatic Cytochrome P450 Expression and Arachidonic Acid Metabolism by Arsenic Trioxide (ATO) in C57BL/6 Mice. In Biological trace element research, 203, 1000-1015. doi:10.1007/s12011-024-04225-1. https://pubmed.ncbi.nlm.nih.gov/38758479/

2. Cui, X, Kawashima, H, Barclay, T B, Morgan, E T, Strobel, H W. . Molecular cloning and regulation of expression of two novel mouse CYP4F genes: expression in peroxisome proliferator-activated receptor alpha-deficient mice upon lipopolysaccharide and clofibrate challenges. In The Journal of pharmacology and experimental therapeutics, 296, 542-50. doi:. https://pubmed.ncbi.nlm.nih.gov/11160642/

3. Elshenawy, Osama H, Anwar-Mohamed, Anwar, Abdelhamid, Ghada, El-Kadi, Ayman O S. 2012. Murine atrial HL-1 cell line is a reliable model to study drug metabolizing enzymes in the heart. In Vascular pharmacology, 58, 326-33. doi:10.1016/j.vph.2012.12.002. https://pubmed.ncbi.nlm.nih.gov/23268359/

4. Amara, Issa E A, Elshenawy, Osama H, Abdelrady, Mohamed, El-Kadi, Ayman O S. 2014. Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57Bl/6 mouse heart. In Toxicology letters, 226, 53-62. doi:10.1016/j.toxlet.2014.01.025. https://pubmed.ncbi.nlm.nih.gov/24472606/