MODIFICATION OF LIPOPEROXIDATIVE EFFECTS OF DICHLOROACETATE AND TRICHLOROACETATE IS ASSOCIATED WITH PEROXISOME PROLIFERATION

被引:27
作者
AUSTIN, EW
OKITA, JR
OKITA, RT
LARSON, JL
BULL, RJ
机构
[1] Pharmacology/Toxicology Graduate Program, College of Pharmacy, Washington State University, Pullman, WA 99164-6510
关键词
TRICHLOROACETATE; DICHLOROACETATE; PEROXISOME PROLIFERATORS; LIPID PEROXIDATION;
D O I
10.1016/0300-483X(94)02926-L
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Pretreatment of male B6C3F(1) mice with clofibric acid (CFA) or trichloroacetic acid (TCA) in the drinking water results in a marked decrease in the lipoperoxidative response as measured by the production of thiobarbituric acid reactive substances (TEARS) in mouse liver homogenates following acute dosing with TCA or dichloroacetic acid (DCA). Pretreatment with TCA or CFA also increased palmitoyl-CoA oxidase activity, microsomal 12-(omega) hydroxylation of lauric acid and expression of P450 4A isoforms. At the doses utilized, DCA-pretreatment did not increase the level of P450 4A protein, or markers of peroxisome proliferation. However, DCA-pretreatment did result in enhanced levels of TEARS, following acute dosing with DCA, compared to controls. Pretreatment with DCA, TCA, or CFA did not alter p-nitrophenol hydroxylation (an assay specific for P450 2E1), and no increases in immunodetectable P450 2E1, 4A, 1A1/2, 2B1/2 or 3A1 protein were observed. Assays from CFA- and TCA-pretreated mice suggest that the reduction in the TEARS response seen in TCA-pretreated animals results from activities associated with peroxisome proliferation. This might result from the induction of systems efficient in scavenging of peroxide intermediates or detoxification of aldehyde by-products of lipid peroxidation.
引用
收藏
页码:59 / 69
页数:11
相关论文
共 42 条
  • [1] EFFECT OF CLOFIBRATE TREATMENT ON GLUTATHIONE CONTENT AND THE ACTIVITY OF THE ENZYMES RELATED TO PEROXIDE METABOLISM IN RAT-LIVER AND HEART
    ANTONENKOV, VD
    GUSEV, VA
    PANCHENKO, LF
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY, 1987, 19 (02): : 187 - 192
  • [2] BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
  • [3] IN-VITRO CYTOTOXICITY OF MONOCHLOROACETATE, DICHLOROACETATE, AND TRICHLOROACETATE AND ITS MODULATION BY HEPATIC PEROXISOME PROLIFERATION
    BRUSCHI, SA
    BULL, RJ
    [J]. FUNDAMENTAL AND APPLIED TOXICOLOGY, 1993, 21 (03): : 366 - 375
  • [4] LIVER-TUMOR INDUCTION IN B6C3F1 MICE BY DICHLOROACETATE AND TRICHLOROACETATE
    BULL, RJ
    SANCHEZ, IM
    NELSON, MA
    LARSON, JL
    LANSING, AJ
    [J]. TOXICOLOGY, 1990, 63 (03) : 341 - 359
  • [5] BULL RJ, 1992, ENV TOXICANTS HUMAN, P184
  • [6] BULL RJ, 1986, ORGANIC CARCINOGENS, P353
  • [7] MEASUREMENT OF CATALASE ACTIVITY IN TISSUE EXTRACTS
    COHEN, G
    DEMBIEC, D
    MARCUS, J
    [J]. ANALYTICAL BIOCHEMISTRY, 1970, 34 (01) : 30 - +
  • [8] HEPATOCARCINOGENICITY OF CHLORAL HYDRATE, 2-CHLOROACETALDEHYDE, AND DICHLOROACETIC ACID IN THE MALE B6C3F1 MOUSE
    DANIEL, FB
    DEANGELO, AB
    STOBER, JA
    OLSON, GR
    PAGE, NP
    [J]. FUNDAMENTAL AND APPLIED TOXICOLOGY, 1992, 19 (02): : 159 - 168
  • [10] THE CARCINOGENICITY OF DICHLOROACETIC ACID IN THE MALE B6C3F1 MOUSE
    DEANGELO, AB
    DANIEL, FB
    STOBER, JA
    OLSON, GR
    [J]. FUNDAMENTAL AND APPLIED TOXICOLOGY, 1991, 16 (02): : 337 - 347