Dietary Allicin Supplementation inhibits Hepatic CYP3A37 in chickens: Evidence from in vitro and in vivo models

Allicin, a natural compound with antibacterial and antioxidant properties, is a promising antibiotic-alternative feed additive. This study investigated its impact on cytochrome P450 3A37 (CYP3A37) in broilers. Broilers were fed a basal diet supplemented with 0, 40, or 80 mg/kg allicin for 42 days. In vivo results revealed a biphasic effect: CYP3A37 activity was induced on day 14 but significantly inhibited on days 28 and 42. This inhibition was accompanied by downregulation of CYP3A37 mRNA and protein expression. Consequently, allicin (80 mg/kg) altered the pharmacokinetics of the CYP3A37 substrate dapsone, increasing its AUC and decreasing its clearance. In vitro assays demonstrated that allicin acts as a non-competitive inhibitor of CYP3A37 with an IC50 of 57.31 μM and a Kᵢ of 85.53 μM, in a time- and concentration-dependent manner. In conclusion, long-term allicin supplementation inhibits CYP3A37, posing a potential risk for drug-drug interactions in veterinary practice.