7-Chloro-4-(phenylselanyl) quinoline reduces renal oxidative stress induced by oxaliplatin in mice

Can J Physiol Pharmacol. 2021 Oct;99(10):1102-1111. doi: 10.1139/cjpp-2021-0090. Epub 2021 May 20.

Abstract

The object of this study was to evaluate the relationship between oxidative damage induced by oxaliplatin (OXA) and the therapeutic potential of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) in kidney of mice. Mice received OXA (10 mg/kg) or vehicle intraperitoneally (days 0 and 2). Oral administration of 4-PSQ (1 mg/kg) or vehicle was performed on days 2 to 14. On day 15 the animals were euthanized and the kidneys and blood were collected. The effect of OXA and (or) 4-PSQ on urea, thiobarbituric acid reactive species, nonprotein thiol (NPSH), and protein carbonyl (PC) levels were investigated. Moreover, renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), δ-aminolevulinic acid dehydratase (δ-ALA-D), and Na+,K+ ATPase activities were evaluated. Our findings revealed an increase on urea levels and significant renal oxidative damage in OXA-induced mice. OXA exposure increased SOD, GPx, and GST activities and caused a reduction on NPSH levels and CAT and GR activities. Na+,K+ ATPase and δ-ALA-D activities were reduced by OXA. 4-PSQ decreased plasmatic urea levels and renal oxidative damage. SOD, GPx, CAT, GR, and Na+,K+ ATPase activities were restored by 4-PSQ. 4-PSQ may be a good prototype for the treatment of OXA-induced renal injury.

Keywords: nephroprotection; néphroprotection; oxaliplatin; oxaliplatine; oxidative stress; quinoline; selenium; stress oxydatif; sélénium.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity
  • Antioxidants / pharmacology*
  • Catalase / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / metabolism
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Oxaliplatin / adverse effects*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Quinolines / pharmacology*
  • Superoxide Dismutase / metabolism

Substances

  • 7-chloro-4-(phenylselanyl) quinoline
  • Antineoplastic Agents
  • Antioxidants
  • Quinolines
  • Oxaliplatin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Transferase