Subchronic Low-Dose Dietary Methoxychlor Exposure Causes Hepatic and Renal Injury in Broilers: In Vivo Evidence and Network Toxicology Predictions.
TL;DR
Overall, subchronic dietary MXC exposure at low concentrations adversely affected broiler growth and produced hepatic and renal injury accompanied by systemic inflammatory and oxidative perturbations.
Abstract
Methoxychlor (MXC) is a persistent organochlorine pesticide that may enter poultry production through contaminated feed. However, the effects of prolonged low-dose dietary exposure in avian species remain poorly characterized. In this study, male broilers were fed diets containing 0, 2, 10, 50, or 200 μg/kg MXC for 42 days. Growth performance, hematological and serum biochemical indices, organ indices, histopathology, and serum inflammatory and oxidative-stress markers were evaluated; network toxicology and molecular docking were used as exploratory computational analyses. MXC treatment produced stage-specific growth effects, with reduced average daily gain during days 22-42 in the 2, 10, and 200 μg/kg groups. At day 42, kidney indices were increased in all MXC-treated groups, and histological examination revealed treatment-related lesions in the liver and kidneys. Serum cytokine and redox markers also changed in a time- and treatment-dependent manner, without a clear monotonic concentration-response pattern. Network analysis based primarily on human databases predicted 239 overlapping MXC-liver-injury candidate targets and prioritized 44 candidate hub targets, including AKT1, SRC, and CASP3, with enrichment of NF-κB- and PI3K-Akt-related pathways. Docking analyses predicted favorable modeled interactions between MXC and six selected candidate hub proteins. Overall, subchronic dietary MXC exposure at low concentrations adversely affected broiler growth and produced hepatic and renal injury accompanied by systemic inflammatory and oxidative perturbations. The computational results are hypothesis-generating and require direct biological validation.