Redox-sensitive and inflammatory pathway modulation by Chrysin confers protection against aflatoxin B1-induced...

This study investigated the protective mechanisms of Chrysin (Ch) against aflatoxin B₁ (AFB₁)-induced hepato-renal toxicity in rats, focusing on oxidative stress, Sirtuin-1 (Sirt-1)/NF-κB signaling, apoptosis, and tissue remodeling pathways. Forty male Wistar albino rats were randomly allocated to Control, Ch, AFB₁, and Ch+AFB₁ groups. Chrysin (25 mg/kg BW /day) was administered orally for 11 days, while AFB₁ (0.5 mg/kg BW /day) for 7 days. AFB₁ exposure induced pronounced hepato-renal injury and histopathological alterations. At the molecular level, it caused excessive oxidative stress, evidenced by glutathione depletion and elevated malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels, indicating lipid peroxidation and oxidative DNA damage. This redox imbalance activated inflammatory signaling, reflected by increased NF-κB p65 and TNF-α, alongside dysregulated Sirt-1 expression, suggesting disruption of redox-sensitive transcriptional control. Persistent oxidative and inflammatory stress further promoted mitochondrial apoptosis, as indicated by upregulated Caspase-3 and Caspase-9, and triggered compensatory proliferation, demonstrated by elevated PCNA and Ki-67 levels. Co-administration of Chrysin mitigated these biochemical and molecular alterations by restoring antioxidant defenses, suppressing NF-κB-mediated inflammation via modulation of the Sirt-1/NF-κB axis, and attenuating apoptotic and proliferative signaling. These molecular improvements were accompanied by preservation of hepatic and renal histoarchitecture. Although the animals exhibited subclinical biochemical and histological stress, no overt clinical illness was observed during the study. In conclusion, AFB₁-induced hepato-renal toxicity is driven by interconnected oxidative, inflammatory, and apoptotic mechanisms. Chrysin provides multi-level protection by modulating these pathways, highlighting its potential as a protective agent against mycotoxin-induced toxic injury.