Effect of cisplatin and cobalt chloride on antioxidant enzymes in the livers of Lewis lung carcinoma-bearing mice: protective role of heme oxygenase

Toxicol Lett. 2003 Mar 3;138(3):235-42. doi: 10.1016/s0378-4274(02)00416-2.

Abstract

Changes in the activities of antioxidant enzymes superoxide dismutase, catalase (CAT), glutathione peroxidase and heme oxygenase (HO) and changes in lipid peroxidation and reduced glutathione (GSH) levels were measured in the livers of control and Lewis lung carcinoma (LLC)-bearing mice 24 h after a single injection of cisplatin or CoCl(2). Treatment with cisplatin induced the same degree of lipid peroxidation and GSH depletion as did CoCl(2) but the antioxidant enzymes were differently involved in cisplatin- and cobalt-induced oxidative stress responses. In cobalt-treated mice the activities of these enzymes were either inhibited or not changed significantly and only the HO activity was increased (5-fold) as a main protective enzyme. In cisplatin-treated animals the antioxidant enzymes were activated but the enhancement of HO and CAT was greater in LLC-inoculated mice. It is suggested that these two enzymes represent the protective response against cisplatin toxicity in the livers of tumor-bearing animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / antagonists & inhibitors
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / metabolism
  • Carcinoma, Lewis Lung / enzymology*
  • Catalase / metabolism
  • Cisplatin / antagonists & inhibitors
  • Cisplatin / pharmacology*
  • Cobalt / pharmacology*
  • Glutathione / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Lipid Peroxides / biosynthesis
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Random Allocation
  • Superoxide Dismutase / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Lipid Peroxides
  • Cobalt
  • Catalase
  • Heme Oxygenase (Decyclizing)
  • Superoxide Dismutase
  • cobaltous chloride
  • Glutathione
  • Cisplatin