Original Investigation of the Biochemical Mechanisms of Ochratoxin A-Induced Nephrotoxicity and Immune Suppression in Pigs Fed Contaminated Maize in Kogi State, North Central Nigeria

Ochratoxin A contamination of stored maize is a persistent food safety and livestock health challenge in North Central Nigeria, and the integrated molecular mechanisms of ochratoxin A-induced nephrotoxicity and concurrent immune suppression in Nigerian pig populations have not been mechanistically characterised. This doctoral study investigated the biochemical mechanisms of ochratoxin A nephrotoxicity and immune suppression in Large White pigs fed naturally contaminated maize at two exposure levels over a twelve-week period in Lokoja, Kogi State. Sixty pigs were divided into control, low-dose (50 ppb ochratoxin A), and high-dose (200 ppb ochratoxin A) groups. Renal tubular biomarkers including urinary N-acetyl-beta-D-glucosaminidase, kidney injury molecule-1, and clusterin were measured weekly. Immunological indices including lymphocyte proliferation, immunoglobulin G and M concentrations, interferon-gamma, and natural killer cell cytotoxicity were assessed monthly. Renal tissue was collected post-mortem for histopathology and caspase-3, caspase-9, and Bcl-2 immunohistochemistry. Ochratoxin A exposure induced a progressive dose-dependent rise in urinary kidney injury molecule-1 from week four, preceding histological tubular necrosis by two weeks. Apoptotic pathway activation confirmed mitochondria-dependent caspase-9 as the primary mechanistic route of tubular cell death. Immunoglobulin concentrations and interferon-gamma were significantly reduced by week eight in both exposed groups, with natural killer cell cytotoxicity reduced by 52% in the high-dose group. The mechanistic dissection of dual nephrotoxic and immunotoxic pathways in this study provides original insights into ochratoxin A livestock pathology and supports regulatory action on permissible mycotoxin levels in Nigerian pig feed. Keywords: ochratoxin A, nephrotoxicity, immune suppression, pigs, kidney injury molecule-1.