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

• Published in: Toxicology (Amsterdam) Vol. 464; p. 153027
• Main Authors: Ebokaiwe, Azubuike Peter, Obasi, Doris Olachi, Njoku, Rex Clovis C., Osawe, Sharon, Olusanya, Olasiende, Kalu, Winner O.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2021
• Subjects: Animals; Antioxidants - metabolism; Cyclophosphamide - toxicity; Immunosuppressive Agents - toxicity; Indoeamine 2,3-dioxygenase; Indoleamine-Pyrrole 2,3,-Dioxygenase - toxicity; Inflammation - chemically induced; Inflammation - prevention & control; Kidney; Kidney - drug effects; Kidney - pathology; Liver; Liver - drug effects; Liver - pathology; Male; Oxidative Stress - drug effects; Oxidative-inflammatory stress; Quercetin - pharmacology; Rats; Rats, Wistar; Tryptophan 2,3-dioxygenase; Oxidative-inflammatory stress; Tryptophan 2,3-dioxygenase; Indoeamine 2,3-dioxygenase; Liver; Kidney
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2021.153027

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.