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Limited protective role of V-PYRRO/NO against cholestasis produced by alpha-naphthylisothiocyanate in mice

  1. Author:
    Liu, J.
    He, Y. Y.
    Chignell, C. F.
    Clark, J.
    Myers, P.
    Saavedra, J. E.
    Waalkes, M. P.

  2. Author Address

    NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. SAIC Frederick, Frederick, MD USA Liu, J, NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA
    1. Year: 2005
    2. Date: JUL 1
  2. Journal: Biochemical Pharmacology
    1. 70
    2. 1
    3. Pages: 144-151
  4. Type of Article: Article
  1. Abstract:

    O-2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) is a liver-selective nitric oxide donor that has been shown to protect against hepatotoxic effects of endotoxin, acetaminophen and cadmium. This study examined the effects of V-PYRRO/NO on alpha-naphthylisothiocyanate (ANIT)-induced hepatotoxicity in mice. Mice were given V-PYRRO/NO via osmotic pumps (5.4 mg/ml; 0.5 mu l/h) starting 24 h before receiving a hepatotoxic dose of ANIT (150 mg/kg in olive oil, i.g.), and continuing for additional 48 h (3-day pumps). V-PYRRO/NO administration partially ameliorated ANIT-induced hepatotoxicity, as evidenced by reduced serum alanine aminotransferase and alkaline phosphatase, markers of liver cell death, and by improved liver pathology. However, V-PYRRO/NO had no effect on ANIT-induced cholestasis, as ANIT-increased serum bilirubin levels and gamma-glutamyl transpeptidase activity were not ameliorated. Microarray and real time RT-PCR analysis revealed that ANIT intoxication altered expression of various genes, including genes encoding metabolic enzymes, transporter proteins, acute phase proteins, inflammation- and, apoptosis-related genes, as well as other genes related to liver injury. V-PYRRO/NO treatment attenuated ANIT-induced elevations in certain inflammation- and apoptosis-related genes, but had no effect on ANIT-induced disturbance on the expression of genes related to metabolism, transport, and acute phase proteins. Thus, the liver-selective NO donor, V-PYRRO/NO, was partially protective against ANIT-induced liver injury, without affecting ANIT-induced cholestasis and cholestasis-related gene expression. Published by Elsevier Inc

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External Sources

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  2. DOI: 10.1016/j.bcp.2005.03.034
  3. View record in Web of Science®
  4. WOS: 000229979500015

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