Protective effects of a superoxide dismutase/catalase mimetic compound against paraquat pneumotoxicity in rat lung

Respirology. 2009 May;14(4):504-10. doi: 10.1111/j.1440-1843.2009.01531.x.

Abstract

Background and objective: EUK-134 is one of the most promising of the superoxide dismutase (SOD)/catalase mimetic compounds. The antioxidant effects of EUK-134 were tested in a rat model of paraquat pneumotoxicity.

Methods: Male Wistar rats (n = 72) were divided into three groups: group 1, controls; group 2, paraquat alone; group 3, paraquat + EUK-134. Paraquat dichloride was administered per os at a dose of 80 mg/kg. EUK-134 was injected intraperitoneally at 10 mg/kg 2 h before the paraquat and again 4 h later at 5 mg/kg.

Results: On days 1, 3 and 5 after treatment with paraquat alone the LDH activity increased (P = 0.0001, P = 0.00001 and P = 0.03, respectively), and the total protein content increased (P = 0.00002, P = 0.001 and P = 0.01, respectively). The levels of acid phosphatase (AcP) in BAL fluid increased on days 1 and 3 (P = 0.006 and P = 0.04). In lung homogenates paraquat alone increased SOD activity on day 1 and decreased it on days 3 and 5. Combined treatment with paraquat and EUK-134 elevated LDH activity on day 3 (significantly less than paraquat alone) and day 5, elevated the total protein content on day 5 only, and did not change AcP activity. The combination of both agents did not alter SOD activity and decreased catalase activity on day 5 significantly less than treatment with paraquat alone (P = 0.05).

Conclusions: EUK-134, a superoxide dismutase/catalase mimetic compound decreased the pneumotoxic effect of paraquat in rats.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Catalase
  • Disease Models, Animal
  • Herbicides / pharmacology*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Organometallic Compounds / pharmacology*
  • Oxidative Stress / drug effects*
  • Paraquat / pharmacology*
  • Rats
  • Rats, Wistar
  • Salicylates / pharmacology*
  • Superoxide Dismutase

Substances

  • Antioxidants
  • EUK-134
  • Herbicides
  • Organometallic Compounds
  • Salicylates
  • Catalase
  • Superoxide Dismutase
  • Paraquat