Integrated pathways of T-2 toxin-induced neurotoxicity and protection by sodium butyrate in quails.

Abstract

BACKGROUND: T-2 toxin, a prevalent mycotoxin in feed, poses severe health risks to poultry. While its systemic toxicity is recognized, its neurotoxic effects in birds, and effective countermeasures, remain underexplored. Sodium butyrate (NaB), a green feed additive, has shown broad biological benefits, but its potential to alleviate T-2-induced neurotoxicity is unclear. OBJECTIVE: This study aimed to investigate the neurotoxic mechanisms of T-2 toxin in quails and evaluate the protective role of sodium butyrate. METHODS: Two-hundred-and-forty 10-day-old quails were randomly assigned to Control, T-2 toxin (0.9 mg/kg), NaB (500 mg/kg), and T-2+NaB groups. After 14 and 28 days, brain tissues were collected for histopathological (hematoxylin-eosin [HE], Nissl, Fluoro-Jade B [FJB] staining) and molecular analyses (RT-qPCR, Western blot, semi-quantitative PCR) to assess oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. RESULTS: T-2 toxin induced severe brain damage, characterized by neuronal vacuolization, loss of Nissl bodies, and degeneration. It concurrently activated oxidative stress (upregulated Nrf2 [nuclear factor erythroid 2-related factor 2], HO-1 [heme oxygenase-1], NQO1 [NAD(P)H: quinone oxidoreductase 1]), neuroinflammation (elevated TNF-α [tumor necrosis factor-alpha], IL-1β [interleukin-1 beta], IL-6 [interleukin-6], IL-18 [interleukin-18]), and ER stress (increased GRP78 [glucose-regulated protein 78], IRE1α [inositol-requiring enzyme 1 alpha], TRAF2 [TNF receptor-associated factor 2], IKKα/β [IκB kinase alpha/beta], XBP1 [X-box binding protein 1]). Sodium butyrate supplementation significantly mitigated these histopathological alterations and downregulated the overactivated molecular pathways across all three axes. CONCLUSION: This study demonstrates that sodium butyrate confers comprehensive neuroprotection against T-2 toxin in quails by co-ordinately alleviating oxidative stress, neuroinflammation, and ER stress. These findings provide a mechanistic basis for using NaB as a dietary intervention to combat mycotoxin-related neurotoxicity in poultry.

Key Findings

• T-2 toxin induces severe neurotoxicity in quails characterized by neuronal damage and degeneration.
• T-2 toxin activates oxidative stress pathways including upregulation of Nrf2, HO-1, and NQO1.
• Sodium butyrate supplementation significantly mitigates brain damage by downregulating oxidative stress, neuroinflammation, and ER stress pathways.

Clinical Significance

Citation

Cao Changyu, Huang Chuying, Li Xinran. Integrated pathways of T-2 toxin-induced neurotoxicity and protection by sodium butyrate in quails. Chemico-biological interactions. 2026-Jul-04.