Intermittent Organophosphate Pesticide Exposure Induces Hepatic Injury in Goats with Subclinical Fatty Liver via Immune Activation and Energy Metabolism Reprogramming.

Abstract

Organophosphate pesticides are widely used in livestock production, yet their impact on the liver, particularly with repeated low-dose exposure in animals with underlying metabolic stress, remains poorly understood. We examined this using a goat model where treated animals received intermittent trichlorfon poisoning followed by antidote rescue, mimicking field conditions. Unexpectedly, our control goats turned out to have fatty liver, forcing us to reframe the study around how OP exposure worsens pre-existing liver damage. Poisoned goats showed aggravated fat accumulation, focal cell death, and inflammatory infiltration, alongside striking blood changes including leukocytosis, microcytic anemia, and an unusual enzyme pattern with falling ALT and rising AST/ALT ratio suggesting mitochondrial injury. Proteomics revealed 326 altered proteins clustering in immune activation, specifically complement proteins C3 and C5 and TNF pathway molecules, and energy metabolism, specifically suppressed oxidative phosphorylation and enhanced glycolysis, with these two processes feeding each other to amplify damage. Spleen, kidney, and intestine also suffered injury. Thus, intermittent OP exposure hits fatty liver hard through combined immune overdrive and metabolic crisis, with proteins such as C3 and GAPDH offering potential markers or therapeutic targets.