Aflatoxin B1 Instigated Redox Imbalance is Accompanied by Amplified Indoleamine 2,3-Dioxygenase/tryptophan Catabolism in the Spleen and Erythrocyte of Male Wistar Rats: Protective Influence of Dietary Rutin.

Introduction: Rutin, a dietary flavonoid, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. The underlying mechanism of protection of rutin against Aflatoxin B1 (AFB1)-induced immunotoxicity is not completely elucidated. This study investigated the protective effect of rutin against Aflatoxin B1 (AFB1)-induced immunotoxicity in male Wistar rats, supported by molecular docking and dynamics simulations.

Methods: Forty male Wistar rats were grouped into five: control (corn oil), AFB₁ (0.75 mg/kg bwt), AFB₁ (1.5 mg/kg bwt), rutin (50 mg/kg bwt), and AFB₁ (1.5 mg/kg bwt) + Rutin (50 mg/kg bwt) orally for 30 days.

Results: AFB₁ exposure increased (p < 0.05) oxidative and inflammatory markers, altered hematological indices, and caused histological damage in the spleen and bone marrow. Elevated indoleamine 2,3-dioxygenase (IDO) activity, reduced CD4+ T cells, and unchanged tryptophan 2,3-dioxygenase (TDO) activity were also observed. Docking revealed strong binding affinities for AFB₁ (-9.5 kcal/mol), rutin (-9.7 kcal/mol), and AFB₁-rutin (-10.4 kcal/mol) with IDO. Rutin co-treatment restored oxidative, inflammatory, and hematological indices, mitigated histological damage, and normalized CD4+ T cells and IDO activity, as supported by computational studies.

Discussion: The activities/expression of immunosuppressive indoleamine 2, 3-dioxygenase is mostly regulated by inflammation and oxidative stress. This study provides new insights into the mechanisms underlying the modulation of immunotoxicity of AFB1 by dietary rutin.