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.

Cyclophosphamide instigated hepatic-renal oxidative/inflammatory stress aggravates immunosuppressive indoleamine 2,3-dioxygenase in male rats: Abatement by quercetin.

The hepatic-renal toxicity associated with cyclophosphamide (CYP) treatment in both animals and humans have been reported. Quercetin, a dietary flavonoid, is known to elicit beneficial health effects. However, the influence of quercetin on the hepatic-renal toxicity associated with CYP-instigated indoleamine 2,3-dioxygenase is unavailable in the literature. The current study evaluated the effects of quercetin on the dysfunctional hepatic-renal status triggered by CYP exposure in rats. Experimental animals were exposed to CYP (100 mg/kg) or co-treated with quercetin (50 mg/kg) every other day for 7 days. Results revealed that quercetin treatment significantly assuaged CYP-mediated oxidative-inflammatory response, as well as augmenting serum levels of thyroid hormones. Additionally, quercetin attenuated CYP-induced reduction in antioxidant enzyme activities and enhanced hepatic-renal function markers, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and levels of urea and creatinine. Quercetin efficiently mitigated CYP-mediated increase in myeloperoxidase (MPO) activity, levels of nitric oxide and interleukin-6 (IL-6) in liver and kidney of rats. CYP-induced increase in the activities of immunosuppressive indoleamine 2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase (TDO) in the tissues was abated in quercetin co-treated rats. In conclusion, Quercetin ameliorated deficits in the hepatic-renal function in CYP-exposed rats by lowering the activities/expression of immunosuppressive IDO and TDO via diminution of oxidative-inflammatory stress.