Effects of phenidone (DuCLOX-2/5 inhibitor) against N-methyl-N-nitrosourea induced mammary gland carcinoma in albino rats

Toxicol Appl Pharmacol. 2018 Jul 15:351:57-63. doi: 10.1016/j.taap.2018.04.019. Epub 2018 Apr 18.

Abstract

The present study was designed to evaluate the effects of phenidone (Dual inhibitor of COX-2 and 5-LOX, DuCLOX-2/5 inhibitor) on various aspects of cancer chemoprevention. Treatment with the phenidone was inquested to validate the implications of dual inhibition of arachidonic acid (AA) metabolism against MNU induced mammary gland carcinogenesis. MNU treated rat showed altered hemodynamic profile, distorted cellular architecture, upregulated inflammatory enzyme markers (COX, LOX, Nitric oxide and hydrogen sulfide) and distorted oxidative stress markers (thiobarbituric acid reactive substances, protein carbonyl, superoxide dismutase, catalase and glutathione). Phenidone treatment regulated histological architecture in the experimental animals similar to control. The treatment with phenidone favorably regulated the levels of inflammatory markers, and oxidative stress markers against toxic treatment. Our findings emphasize the potential role of phenidone in suppression of mammary gland carcinoma against the deleterious effects of MNU.

Keywords: Cyclooxygenase; DuCLOX-2/5; Lipoxygenase; Mammary gland; Oxidative stress; Phenidone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase* / metabolism
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Female
  • Lipoxygenase Inhibitors / therapeutic use*
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / metabolism
  • Methylnitrosourea / toxicity*
  • Pyrazoles / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Treatment Outcome

Substances

  • Cyclooxygenase 2 Inhibitors
  • Lipoxygenase Inhibitors
  • Pyrazoles
  • Methylnitrosourea
  • Arachidonate 5-Lipoxygenase
  • ALOX5 protein, human
  • phenidone