Gemfibrozil attenuates doxorubicin induced toxicity in renal tissues of male rats by reducing the oxidative insult and inflammation

Biotech Histochem. 2020 Oct;95(7):532-539. doi: 10.1080/10520295.2020.1730967. Epub 2020 Apr 3.

Abstract

Nephrotoxicity is a significant side effect of doxorubicin (DXN) treatment. We investigated the protective effect of gemfibrozil (GEM) co-administration with DXN on DXN induced nephrotoxicity. We divided 28 male Wistar rats into four groups of seven. Group 1 received normal saline for 2 weeks. Group 2 received 15 mg/kg DXN for 2 weeks. Group 3 received DXN + GEM for 2 weeks. Group 4 received GEM for 2 weeks. On day 15 of the experiment, blood samples were collected, animals were sacrificed and kidneys were excised for biochemical and histological evaluation. We measured serum creatinine, blood urine nitrogen, renal malondialdehyde, nitric oxide, glutathione, superoxide dismutase, glutathione peroxidase, catalase, tumor necrosis factor-α and interleukin-1β. GEM administration mitigated DXN induced nephrotoxicity. GEM co-administered with DXN attenuated the inflammatory and oxidative responses associated with DXN induced nephrotoxicity.

Keywords: doxorubicin; gemfibrozil; inflammation; kidney; nephrotoxicity; oxidative stress; rat.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Cytochrome P-450 CYP2C8 Inhibitors / pharmacology
  • Doxorubicin / toxicity*
  • Gemfibrozil / pharmacology*
  • Inflammation / chemically induced*
  • Inflammation / drug therapy
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Male
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Wistar

Substances

  • Antibiotics, Antineoplastic
  • Cytochrome P-450 CYP2C8 Inhibitors
  • Doxorubicin
  • Gemfibrozil