Hepatic peroxisome proliferation in rodents and its significance for humans

Bentley, Philip; Calder, I. C.; Elcombe, Cliff; Grasso, P.; Stringer, D.A.; Wiegand, Herbert

doi:10.1016/0278-6915(93)90225-n

Cited by 253 publications

(149 citation statements)

References 186 publications

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“…33,34 In conclusion, peroxisome proliferators upregulate L-FABP expression through activation of peroxisome proliferator activated receptors. 35 Peroxisome proliferators also increase intracellular levels of peroxisomes, 36 resulting in an overproduction of hydrogen peroxide. 37,38 Hydrogen peroxide, being a precursor of ROS, may contribute to the hepatocarcinogenic effects of peroxisome proliferators.…”

Section: Discussionmentioning

confidence: 99%

Antioxidative function of L-FABP in L-FABP stably transfected Chang liver cells

et al. 2005

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C ellular oxidative stress is one of the factors responsible for the propagation of liver diseases, such as hepatitis, cirrhosis, and hepatoma. 1 Several primary antioxidant defense systems such as superoxide dismutase (SOD), catalase, glutathione (GSH), and glutathione peroxidase are present intracellularly. These systems scavenge reactive oxygen species (ROS) such as hydrogen peroxide, superoxide, lipid peroxides, and free radicals. Exposure to oxidative stress may, however, deplete the cellular antioxidant capacity. Therefore, other antioxidant defense systems are expected to play an important role in oxidative stress.Liver fatty acid binding protein (L-FABP) is a 14-kd protein found abundantly in the cytoplasm and the nucleus of hepatocytes. 2,3 L-FABP is very likely to be an effective endogenous antioxidant, because it has high affinity and capacity to bind long-chain fatty acid oxidation products. 4,5 Hepatocyte L-FABP concentration could be as high as 0.4 mmol/L, 6 and it contains a large number of reducing amino acid residues (1 cysteine and 7 methionine residues) in its molecular structure. With an accessible volume enclosed by the molecular surface of L-FABP of 28,600 Å 3,7 the concentration of total methionine residues in L-FABP could be as high as approximately 400 mmol/L. Methionine and cysteine amino acids are regarded as cellular scavengers of activated xenobiotics and

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Section: Discussionmentioning

confidence: 99%

Antioxidative function of L-FABP in L-FABP stably transfected Chang liver cells

et al. 2005

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“…Using 3 hepatocarcinogens, 2-AAF, 3'-Me-DAB, and DL-ethionine, at 3 dose levels, it was clearly indicated that the degree of induction of GST-P-positive foci and nodules in the medium-term bioassay system corresponds with the incidences of hepatocellular carcinomas as revealed by longterm carcinogen exposure (35). A precise dose-response study was also performed using 2-AAF as a model compound to compare the results with the EDO, mega-mouse study of hepatocarcinogenicity (44), and the reliability of our system was again confirmed (51 4 carcinogenic peroxisome proliferators, and tamoxifen did not enhance development of GST-P-positive foci development. With regard to the carcinogenicity of nonmutagenic peroxisome proliferators, it is important to remember that they depress GST-P expression, and the lesions associated with their hepato- (Table III).…”

Section: Marker Lesionsmentioning

confidence: 91%

Review Article: A Medium-Term Rat Liver Bioassay as a Rapid In Vivo Test for Carcinogenic Potential: A Historical Review of Model Development and Summary of Results from 291 Tests

Shirai

1997

Toxicol Pathol

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“…This contrasts with the effects of peroxisome proliferators and high doses of certain complex vegetable and animal oils (7,17). This difference together with the absence of visual lipid accumulation in the liver of mice fed the Lorenzo's Oil-supplemented diets may indirectly suggest that the hepatic peroxisomal ␤-oxidation capacity in treated mice was not overloaded by the excess of erucic and oleic acids.…”

Section: Discussionmentioning

confidence: 97%