Intermediate filament protein expression pattern and inflammatory response changes in kidneys of rats receiving doxorubicin chemotherapy and quercetin. (15th May 2018)

• Record Type: Journal Article
• Authors: Khalil, Samah R.; Mohammed, Amany Tharwat; Abd El-fattah, Amir H.; Zaglool, Asmaa W.
• Is Part Of: Toxicology letters. Volume 288(2018)
• Page Start: 89
• Page End: 98
• Publication Date: 2018-05-15
• Subjects: Doxorubicin -- Intermediate filament proteins -- Myeloperoxidase -- Podocytes -- Quercetin; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.02.024
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Doxorubicin treatment induces nephrotoxic effects and inflammation in male rats. Doxorubicin disturbs the mRNA expression of the intermediate filament proteins. Quercetin exhibits a nephroprotective effect and attenuates the inflammation. Quercetin successfully attenuates the doxorubicin-induced podocyte injury. Quercetin provides a prophylaxis role for use against doxorubicin nephrotoxicity. Abstract: The aim of this study was to explore the potential effects of quercetin (QUR) on doxorubicin (DOX)-induced nephrotoxicity. Fifty male rats were assigned to five groups (10 rats each): a control group, a DOX-treated group (total dose, 15 mg/kg bw, intraperitoneally), a QUR-treated group (50 mg/kg bw/day, orally), a prophylaxis co-treated group, and a therapeutic co-treated group. Biochemical parameters and renal function were measured. Moreover, kidney tissues were homogenized for inflammatory marker evaluation and real-time qPCR analysis to determine the changes in intermediate filament protein mRNA levels (desmin, vimentin, connexin 43 and nestin). QUR exhibited a significant nephroprotective effect, particularly when it was administered prior to and simultaneously with DOX treatment (prophylaxis co-treated group). This role was biochemically demonstrated by the significant modulation of DOX-induced body weight loss, hypoproteinemia, and elevated serum creatinine and urea. Moreover, QUR attenuated the inflammatory response as shown by decreased renal nitric oxide, tumor necrosis factor-α production and myeloperoxidase activity elicited by DOX injection. These biochemical improvements were accompanied by a significant histopathological restoration of rat kidney tissue and successful down-regulation of the intermediate filament protein mRNA levels, indicating amelioration of DOX-induced podocyte injury. Taken together, these results conclusively demonstrated that QUR administration has a prophylactic effect on DOX-induced injury in the rat kidney.