Quercetin attenuates cyclophosphamide induced-immunosuppressive indoleamine 2,3-dioxygenase in the hippocampus and cerebral cortex of male Wister rats.

This study investigated the protective effect of quercetin against cyclophosphamide-induced immunosuppressive indoleamine 2,3-dioxygenase (IDO) via the mechanism of oxidative-inflammatory stress and behavioral indices. Cyclophosphamide (CYP) was administered to male Wister rats at a dose of 100 mg/kg with or without quercetin 50 mg/kg every other day for 7 days. Experimental techniques including western blotting, immunohistochemistry analysis, and inflammatory and oxidative stress marker assays were carried out. We also conducted behavioral analyses such as open field, tail suspension, and Y-maze tests for cognitive assessment. The results indicated that quercetin attenuated oxidative-inflammatory stress induced by CYP in the hippocampus and cerebral cortex of male Wister rats by augmenting the activities of antioxidant enzymes and suppressing lipid peroxidation as well as inflammatory mediators such as interleukin-6 and interferon-γ. Concomitantly, quercetin partially prevented the alteration in brain tissue histological architecture and mitigated the activities of IDO/tryptophan 2,3-dioxygenase (TDO) and protein expression of IDO1. This was corroborated by the IDO-quercetin model obtained in silico, revealing a favorable inhibitory interaction between quercetin and the enzyme. Finally, the results of behavioral tests suggested that quercetin significantly prevented the depressive-like posture of the CYP-treated rats. Our study for the first time revealed that quercetin ameliorates the effect of CYP-instigated IDO/TDO activities in the cerebral cortex and hippocampus via restoration of antioxidant enzymes and preventing oxidative-inflammatory stress.

The mechanism of the neuroprotective effect of zinc against cadmium-induced behavioral impairments in male Wister rats: Focus on tryptophan degradation pathway, oxidative-inflammatory stress, and histologic evidence.

The present study investigated the attenuating effects of Zn following Cd-exposure in the activities/expression of indoleamine 2, 3-dioxygenase (IDO), tryptophan 2, 3-dioxygenase (TDO), oxidative-inflammatory response, behavioral indices and histologic architecture in cerebral cortex and hippocampus of male rats. Adult male Wistar rats were exposed to 200 µg/L and 100 µg/L of Cd and/or Zn in drinking water for 42 days. Cd exposure significantly increased IDO and TDO activities, IDO 1 protein expression, inflammatory response, with attendant disruption in antioxidant systems and concomitant elevation in malondialdehyde (MDA) levels in the cerebral cortex and hippocampus. Following Zn co-treatment, Cd-mediated increase in IDO 1 protein expression, IDO, and TDO activities, and decrease in antioxidant enzymes, and an increase in markers of inflammatory response and MDA production were significantly (p < 0.05) reversed compared with control. Moreover, altered behavioral indices and histological architecture of brain sections following Cd exposure was evidently (p < 0.05) prevented by Zn co-treatment relative to control. Overall, Cd-induced alterations in IDO 1 expression, IDO and TDO activities, oxidative-inflammatory response, behavioral indices, and histological architecture in the cerebral cortex and hippocampus of rats within the time course of the investigation were prevented by Zn co-treatment.