Profiling of hepatic gene expression in rats treated with fibric acid analogs

Single and chronic administration of ciprofibrate or of ciprofibrate-glycinate in male Fischer 344 rats: Comparison of the effects on morphological and biochemical parameters in liver and blood

“…With both substances the well known fibrate effects on liver weights and on liver histology (hypertrophy of the hepatocytes, increased eosinophilia of the cytoplasm because of a pronounced proliferation of the peroxisomes and mitochondria) [13][14][15][16]19,26,54,55] were reproduced also in the present investigation. Additionally, after fibrate treatment a remarkable increase was observed with the kidney weights.…”

“…Their therapeutic use, however, can produce adverse effectslike gastrointestinal disorders, myalgia, myositis and increased risk of developing gallstones. Large doses can even cause hepatocellular carcinoma in rodents [9,10].The toxic but also the therapeutic effects of the fibrates are attributed to their action on so-called peroxisome proliferatoractivated receptors (pPARs),but also to signallingthrough other receptors or through non-receptor pathways [11][12][13].As a typical effect, after treatment of rats with fibrates a pronounced proliferation of peroxisomes in the livers can be observed [see e.g. [14][15][16].…”

Unmetabolized fenofibrate, but not fenofibric acid, activates AMPK and inhibits the expression of phosphoenolpyruvate carboxykinase in hepatocytes

“…Previous studies have demonstrated that fenofibrate-treated animals with or without impaired glucose tolerance show a decrease in PEPCK activity or expression (Dana et al 2001;Srivastava 2009;Cornwell et al 2004) and glucose production (Matsuura et al 2004) in the liver. Consistent with these reports we observed that fenofibrate treatment decreased PEPCK mRNA expression in the liver of wild-type mice, although the treatment term was much shorter than those of previous studies.…”

“…Matsuura and coworkers have reported that in spontaneous model rats of NIDDM, fenofibrate treatment significantly decreased the glucagon-induced hepatic glucose production (Matsuura et al 2004). Furthermore, fenofibrate has been reported to reduce PEPCK gene expression in the livers of animal models of impaired glucose metabolism (Dana et al 2001;Srivastava 2009;Cornwell et al 2004). Hypolipidemic drugs, including fenofibrate, in the fibrate class are considered to act as specific activators of the peroxisome proliferators-activated receptors (PPAR) α and to increase transcription of genes that facilitate fatty acid metabolism.…”

Investigating the Mechanistic Basis for Hepatic Toxicity Induced by an Experimental Chemokine Receptor 5 (CCR5) Antagonist Using a Compendium of Gene Expression Profiles

“…A compendium of liver gene expression responses to treatment with 65 chemicals was assembled from multiple studies (Table 1, Waring et al, 2003;Cornwell et al, 2004;Jolly et al, 2004). In addition to the 2 short chain fatty acids described in Jolly et al, 4 other short chain fatty acids (4-pentenoic acid, 20 mg/kg; n-octanoic acid, 700 mg/kg; pivalate, 500 mg/kg; propionic acid, 700 mg/kg) were examined in the same paradigm.…”