Epigallocatechin-3-gallate as a hepatoprotective agent against ochratoxin a: modulating ER stress and...

Ochratoxin A(OTA) is one of the most common foodborne mycotoxins worldwide. Although the kidney is its primary target organ, OTA also causes significant hepatotoxicity in both animals and humans. This study investigated the molecular mechanisms underlying OTA-induced hepatotoxicity, focusing particularly on endoplasmic reticulum(ER) stress and inflammatory signaling pathways, and evaluated the hepatoprotective potential of epigallocatechin-3-gallate(EGCG), a natural polyphenol with antioxidant and anti-inflammatory properties. Thirty Albino Wistar rats were divided into five groups(n = 6 each): a vehicle control group, an OTA(0.5 mg/kg/day, 14 days), OTA(0.5 mg/kg/day) combined with EGCG(50 or 100 mg/kg/day) and 100 mg/kg as an EGCG control. All treatments were administered once daily by oral gavage for 14 days. Oxidative stress markers(glutathione [GSH] and malondialdehyde[MDA]) and glucose-regulated protein 78(GRP78),inositol-requiring enzyme 1α(IRE1α),nuclear factor kappa B(NF-κB), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) mRNA expression were examined in liver tissue together with histopathological assessment of liver tissue. OTA induced hepatic fibrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation, all of which were markedly alleviated by EGCG treatment. OTA significantly reduced GSH levels while elevating MDA levels, reflecting oxidative stress and upregulated IRE1α,NF-κB, TNF-α, and IL-6 expression. EGCG co-administration produced a dose-dependent suppression in IRE1α, NF-κB, TNF-α,and IL-6 expression levels. Notably, GRP78 expression was further elevated with EGCG treatment. Histopathological findings supported the biochemical data, confirming that EGCG attenuated OTA-induced liver damage. This study demonstrated that OTA-induced hepatotoxicity may mediated, at least in part, through modulation of ER stress and NF-κB-driven inflammatory cascades, and that EGCG demonstrated dose-dependent protection by attenuating these responses.