Pyridine induction of cytochrome P450 1A1, iNOS and metallothionein in Syrian hamsters and protective effects of silymarin


Tunca R., Sozmen M., Citil M. , Karapehlivan M., Erginsoy S., Yapar K.

EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, cilt.61, ss.243-255, 2009 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 61 Konu: 3
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1016/j.etp.2008.05.011
  • Dergi Adı: EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY
  • Sayfa Sayısı: ss.243-255

Özet

An in vivo assessment for the protective effects of silymarin for pyridine toxicity was investigated through cytochrome P450 isoform CYP1A1 and inducible nitric oxide synthase (iNOS) activity prevention. Moreover, the effect of pyridine-induced oxidative stress on metallothionein I-II (MT), a scavenger of oxygen-derived free radicals, was investigated. Forty Syrian hamsters were allocated into 4 groups. Syrian hamsters were dosed with pyridine (400 mg/kg) intraperitoneally with and without silymarin (200 mg/kg daily by gavage) for 4 days. Pyridine induced diffuse degeneration and necrosis of the proximal and distal renal tubular cells; cloudy swelling, necrosis and hepatocellular atypia of the liver; and degenerative changes in the myocardium. The degree of pathological alterations was less severe with simultaneous silymarin application. CYP1A1, iNOS and MT expression levels were elevated in liver, kidney and heart in response to acute pyridine toxicity. Silymarin application abolished or significantly suppressed the induction of CYP1A1, iNOS and MT expressions in liver, kidney and heart of the pyridine-treated Syrian hamsters. Enhanced synthesis of MT by pyridine possibly implies a purposive cellular response to prevent damage caused by oxygen radicals. However, silymarin significantly reduced the oxidative-stress-inducing effect of pyridine as reflected by decreased synthesis of MT. These results suggest that through oxidant generation, pyridine may cause alteration of the metabolic ways, including nitric oxide-mediated CYP1A1 activity. (c) 2009 Elsevier GmbH. All rights reserved.