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Involvement of endogenous nitric oxide in myeloperoxidase mediated benzo(a)pyrene induced polymorphonuclear

Abhai Kumar1, Suman Patel, Yogendra Kumar Gupta

  • 1Industrial Toxicology Research Centre (ITRC), Lucknow 226 001, UP, India.

Molecular and Cellular Biochemistry
|March 17, 2006
PubMed

Insights

Benzo(a)pyrene exposure increases cellular injury in polymorphonuclear leukocytes (PMNs) via nitric oxide (NO) production. Cytochrome P-450 1A1 (CYP1A1) appears to induce inducible nitric oxide synthase (iNOS) expression, contributing to this PMN damage.

Area of Science:

  • Toxicology
  • Biochemistry
  • Immunology

Background:

  • Benzo(a)pyrene is a polycyclic aromatic hydrocarbon known to cause cellular damage.
  • Polymorphonuclear leukocytes (PMNs) play a crucial role in inflammatory and immune responses.
  • Nitric oxide (NO) is a signaling molecule implicated in various cellular processes, including inflammation and injury.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) in benzo(a)pyrene-induced cellular injury in PMNs.
  • To elucidate the relationship between cytochrome P-450 1A1 (CYP1A1) and inducible nitric oxide synthase (iNOS) in this context.

Main Methods:

  • PMNs were isolated from Wistar rats treated with or without benzo(a)pyrene.
  • Enzyme activities (catalase, SOD, GST, MPO) and nitrite content were measured.
  • Expression of iNOS and CYP1A1 was analyzed using NOS inhibitors (aminoguanidine, L-NAME) and a CYP1A1 inhibitor (alpha-naphthoflavone).

Main Results:

  • Benzo(a)pyrene treatment significantly increased nitrite content, SOD, MPO, GST activities, and iNOS and CYP1A1 expression in PMNs.
  • NOS inhibitors (AG, L-NAME) reduced nitrite content, MPO activity, and iNOS expression, but not CYP1A1 expression.
  • CYP1A1 inhibition significantly decreased iNOS expression in benzo(a)pyrene-treated PMNs.

Conclusions:

  • CYP1A1 induces iNOS expression, leading to endogenous NO generation.
  • This NO production contributes to the augmentation of myeloperoxidase-mediated benzo(a)pyrene-induced injury in PMNs.
  • The findings highlight a novel mechanism of benzo(a)pyrene toxicity involving CYP1A1-iNOS-NO pathway.

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