Species differences in induction of hepatic enzymes by BM 17.0744, an activator of peroxisome proliferator-activated receptor alpha (PPARα)

1999 ◽  
Vol 73 (8-9) ◽  
pp. 440-450 ◽  
Author(s):  
Kirstin Meyer ◽  
Alfred Völkl ◽  
Richard Endele ◽  
Hans-Frieder Kühnle ◽  
Johannes Pill
Keyword(s):  
Species Differences ◽  
Peroxisome Proliferator ◽  
Hepatic Enzymes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

scholarly journals Peroxisome proliferator-activated receptor alpha: role in rodent liver cancer and species differences

1999 ◽  
Vol 22 (1) ◽  
pp. 1-8 ◽  
Author(s):  
PR Holden ◽  
JD Tugwood
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Species Differences ◽  
Plasma Cholesterol ◽  
Specific Gene ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apparent Lack ◽  
Receptor Alpha ◽  
Rats And Mice

Peroxisome proliferators (PPs) are chemicals of industrial and pharmaceutical importance that elicit liver carcinogenesis by a non-genotoxic mechanism. One of the intriguing properties of PPs is that the pleiotropic effects of these compounds (including increased DNA synthesis and peroxisome proliferation) are seen in rats and mice only, but not humans. It is important to determine the risks to humans of environmental and therapeutic exposure to these compounds by understanding the mechanisms of non-genotoxic hepatocarcinogenesis in rodents. To understand this apparent lack of human susceptibility, attention has focused on the peroxisome proliferator-activated receptor alpha (PPARalpha), which appears to mediate the effects of PPs in rodents. It is also known to mediate the hypolipidaemic effects that fibrate drugs exert on humans with elevated plasma cholesterol and triglyceride levels. Human PPARalphas share many functional characteristics with the rodent receptors, in that they can be transcriptionally activated by PPs and regulate specific gene expression. However, one key difference is that PPARalpha is less abundant in human than in rodent liver, which has led to the suggestion that species differences result from quantitative differences in gene expression. In this review we describe the effects of PPs and what is known of the molecular mechanisms of action and species differences with respect to rodents and man. Attention will be given to differences in the amounts of PPARalpha between species as well as the 'qualitative' aspects of PPARalpha-mediated gene regulation which might also explain the activation of some genes and not of others in human liver by PPs.

Role of peroxisome proliferator-activated receptor alpha (PPARα) and PPARα-mediated species differences in triclosan-induced liver toxicity

2018 ◽  
Vol 92 (11) ◽  
pp. 3391-3402 ◽  
Author(s):  
Yangshun Tang ◽  
Michelle M. Vanlandingham ◽  
Yuanfeng Wu ◽  
Frederick A. Beland ◽  
Greg R. Olson ◽  
...  
Keyword(s):  
Species Differences ◽  
Liver Toxicity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha
Sign in / Sign up

Export Citation Format

Share Document