Effects of gamma-hexachlorocyclohexane and L-3,3 ',5-triiodothyronine on rat liver cytochrome P4502E1-dependent activity and content in relation to microsomal superoxide radical generation

Effects of gamma-hexachlorocyclohexane and L-3,3 ',5-triiodothyronine on rat liver cytochrome P4502E1-dependent activity and content in relation to microsomal superoxide radical generation

Author Fernandez, Virginia Google Scholar
Massa, Laura Google Scholar
Quinones, Luis Google Scholar
Simon-Giavarotti, Karin A. Google Scholar
Giavarotti, Leandro Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Azzalis, Ligia Ajaime Autor UNIFESP Google Scholar
Junqueira, Virginia Berlanga Campos Autor UNIFESP Google Scholar
Videla, Luis A. Google Scholar
Institution Univ Chile
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Liver microsomal cytochrome P4502E1-dependent p-nitrophenol (PNP) hydroxylation and expression of cytochrome P4502E1 were studied in rats subjected to gamma-hexachlorocyclohexane (HCCH) or L-3,3,5-triiodothyronine (T-3) administration as a possible mechanism contributing to superoxide radical (O-2(.-)) generation. HCCH treatment (a single dose of 40 mg/kg body wt) produced a 43% increase in the content of total cytochrome P450, whereas T-3 (daily doses of 0.1 mg/kg body wt for two consecutive days) led to a 37% decrease. NADPH-dependent O-2(.-) generation was elevated by HCCH and T-3, expressed as either per mg of protein or per nmol of cytochrome P450, with a 135% enhancement in the O-2(.-) production/superoxide dismutase (SOD) activity ratios being observed in both conditions. This was partly due to depression of SOD activity. Concomitantly, the molecular activity of NADPH-cytochrome p450 reductase was enhanced by 90 and 69% by HCCH and T-3, respectively. In these conditions, microsomal PNP hydroxylation showed increases of 58 and 45% in HCCH- and T-3-treated rats over control values, respectively, with a parallel 31% (HCCH) and 41% (T-3) enhancement in the content of cytochrome P4502E1 assessed by western immunoblotting. We conclude that HCCH and T-3 enhance the expression and activity of cytochrome P4502E1 and that of NADPH-cytochrome P450 reductase in rat liver, regardless of the changes in total cytochrome P450 content, representing major contributory mechanisms to microsomal NADPH-dependent O-2(.-) generation.
Keywords gamma-hexachlorocyclohexane
L-3,3 ',5-triiodothyronine
superoxide radical
cytochrome P4502E1
rat liver
Language English
Date 2003-01-01
Published in Biological Research. Santiago: Sociedad Biolgia Chile, v. 36, n. 3-4, p. 359-365, 2003.
ISSN 0716-9760 (Sherpa/Romeo, impact factor)
Publisher Sociedad Biolgia Chile
Extent 359-365
Origin http://dx.doi.org/10.4067/S0716-97602003000300007
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000186644200007
SciELO ID S0716-97602003000300007 (statistics in SciELO)
URI http://repositorio.unifesp.br/11600/42825

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