Integrative Transcriptomics of Hepatic Drug Metabolism Enzymes in Cattle Exposed to Pyrethroid Contaminated Pastures in Delta State

Pyrethroid insecticides including cypermethrin and deltamethrin are extensively applied for ectoparasites control and crop protection in Delta State, South South Nigeria, resulting in pasture contamination that exposes grazing cattle to chronic sub-therapeutic doses. Hepatic cytochrome P450 enzymes are primarily responsible for pyrethroid metabolism and their induction or inhibition by persistent chemical exposure can substantially alter the pharmacokinetics of co-administered veterinary drugs, creating drug interaction risks with clinical and food safety implications. This study characterised the hepatic transcriptomic response to chronic pyrethroid exposure in cattle naturally grazing contaminated pastures in Delta State, with specific focus on CYP450, UDP-glucuronosyltransferase, and glutathione S-transferase gene expression and its functional consequences on drug metabolism. Thirty cattle from pyrethroid-contaminated farms and 15 age-matched controls from non-contaminated farms in Anambra State were enrolled. Liver biopsies were collected under sedation and subjected to RNA sequencing using Illumina NovaSeq. Pyrethroid body burden was confirmed by GC-MS quantification of 3-phenoxybenzoic acid in urine as a metabolic biomarker. In vivo drug metabolism was characterised using midazolam as a CYP3A4 probe substrate. Transcriptomics identified significant upregulation of CYP3A4, CYP2B6, CYP1A2, and UGT1A1 in exposed cattle, with validated qRT-PCR confirming 3.2 to 7.8 fold induction of key CYP genes. Midazolam pharmacokinetics showed significantly reduced area under the curve and shorter half-life in exposed cattle, confirming functionally relevant enzyme induction. These findings establish that pasture pyrethroid exposure induces hepatic drug-metabolising enzyme expression in Nigerian cattle, with direct implications for veterinary drug efficacy and food safety withdrawal period guidelines. Keywords: transcriptomics, pyrethroid, drug metabolism, CYP450, Delta State.