Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High plasma level of triglycerides (TGs) is a common feature in atherosclerosis, obesity, diabetes, alcoholism, stress, and infection. Since mitochondria have been implicated in cell death under a variety of metabolic disorders, we examined liver mitochondrial functions in hypertriglyceridemic transgenic mice. Hypertriglyceridemia increased resting respiration and predisposed to mitochondrial permeability transition (MPT). Ciprofibrate therapy reduced plasma TG levels, normalized respiration, and prevented MPT. The higher resting respiration in transgenic mitochondria remained in the presence of the adenine nucleotide carrier inhibitor, carboxyatractyloside, bovine serum albumin, and the uncoupling proteins (UCPs) inhibitor, GDP. UCP2 content was similar in both control and transgenic mitochondria. We propose that faster resting respiration represents a regulated adaptation to oxidize excess free fatty acid in the transgenic mice.
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PMID:Hypertriglyceridemia increases mitochondrial resting respiration and susceptibility to permeability transition. 1474 Aug 93

Ciprofibrate is a well-known drug used to normalize lipid parameters and fibrinogen in atherosclerosis patients. In laboratory rodents such as rats or mice, ciprofibrate exhibits peroxisome proliferator activity. However, to date, no clear alterations or side effects caused by ciprofibrate have been noted in humans. In order to further investigate such possible relationships, we studied the effects of sustained ciprofibrate treatment in jerboas (Jaculus orientalis). In these rodents, ciprofibrate does not induce hepatomegaly or promote liver cell DNA replication, confirming that this species more closely resembles humans than do rats or mice. The jerboas were treated daily with ciprofibrate at 3 mg/kg body weight for 4 weeks. Subcellular markers, clinical enzymes and enzymatic antioxidant defenses were then assessed. The results showed a strong decrease in peroxisomal catalase activity and an increase in the level of malondialdehyde (a stress biomarker). Moreover, ciprofibrate in vivo and in vitro inhibited D-3-hydroxybutyrate dehydrogenase, a mitochondrial enzyme of the ketone body interconversion that is important in redox balance (NAD+/NADH+H+ ratio). In conclusion, under these conditions, ciprofibrate induced alterations in the liver oxidative metabolism.
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PMID:Sensitivity of liver metabolism in jerboa (Jaculus orientalis) to ciprofibrate, a peroxisome proliferator. 2147 72


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