Intermediate filament protein expression pattern and inflammatory response changes in kidneys of rats receiving doxorubicin chemotherapy and quercetin

Toxicol Lett. 2018 May 15:288:89-98. doi: 10.1016/j.toxlet.2018.02.024. Epub 2018 Feb 21.

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.

Keywords: Doxorubicin; Intermediate filament proteins; Myeloperoxidase; Podocytes; Quercetin.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use
  • Antibiotics, Antineoplastic / toxicity*
  • Antioxidants / pharmacology*
  • Doxorubicin / antagonists & inhibitors*
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity*
  • Intermediate Filament Proteins / biosynthesis*
  • Intermediate Filament Proteins / drug effects
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control
  • Kidney Function Tests
  • Male
  • Nephritis / chemically induced
  • Nephritis / prevention & control
  • Podocytes / drug effects
  • Podocytes / pathology
  • Podocytes / ultrastructure
  • Quercetin / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antibiotics, Antineoplastic
  • Antioxidants
  • Intermediate Filament Proteins
  • RNA, Messenger
  • Doxorubicin
  • Quercetin