Mechanisms of Action of Absorbable Hypolipidemic Drugs

Sirtori, Cesare R.

doi:10.1007/978-1-4613-2459-1_19

Cited by 3 publications

(2 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical findings, at times disappointing (FIELD—Fenofibrate Intervention and Event Lowering in Diabetes—study) [ 62 ], have been hampered by inappropriate patient selection and, possibly, by the use of non-optimal drug formulations [ 63 , 64 ]. On the other hand, long-term re-evaluation of most recent studies, particularly the ACCORD—Action to Control Cardiovascular Risk in Diabetes—trial with fenofibrate, has clearly indicated that the agent has a heterogeneous response, but may have a valid indication in reducing CVD in appropriately selected patients, i.e., those with diabetes, hypertriglyceridemia and low HDL-C [ 65 ].…”

Section: Ppar-α: Fibrates and Omega-3 Fatty Acids In The Metabolicmentioning

confidence: 99%

“…The efficacy of fibrates on CV prevention has been disputed, mainly on the ground of studies on non-selected patients [ 63 , 64 ]. Long-term re-evaluation of some of the most recent trials has clearly confirmed that fenofibrate in particular may have a valid indication in reducing CVD in patients with diabetes, hypertriglyceridemia and low HDL-C [ 65 ].…”

Section: Ppar-α: Fibrates and Omega-3 Fatty Acids In The Metabolicmentioning

confidence: 99%

See 1 more Smart Citation

PPAR Agonists and Metabolic Syndrome: An Established Role?

Botta

Audano

Sahebkar

et al. 2018

IJMS

194

129

View full text Add to dashboard Cite

Therapeutic approaches to metabolic syndrome (MetS) are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs) are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs), blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate) and omega-3 fatty acids, are powerful TG-lowering agents. They mainly affect TG catabolism and, particularly with fibrates, raise the levels of high-density lipoprotein cholesterol (HDL-C). PPAR-γ agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-α/δ agonists, e.g., elafibranor, have been designed to achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to the insulin-sensitizing and antihyperglycemic effects of glitazones. They also hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD) which is closely associated with the MetS. The PPAR system thus offers an important hope in the management of atherogenic dyslipidemias, although concerns regarding potential adverse events such as the rise of plasma creatinine, gallstone formation, drug–drug interactions (i.e., gemfibrozil) and myopathy should also be acknowledged.

show abstract

Section: Ppar-α: Fibrates and Omega-3 Fatty Acids In The Metabolicmentioning

confidence: 99%

Section: Ppar-α: Fibrates and Omega-3 Fatty Acids In The Metabolicmentioning

confidence: 99%

PPAR Agonists and Metabolic Syndrome: An Established Role?

Botta

Audano

Sahebkar

et al. 2018

IJMS

194

129

View full text Add to dashboard Cite

show abstract

Inhibition instead of enhancement of lipid peroxidation by pretreatment with the carcinogenic peroxisome proliferator nafenopin in rat liver exposed to a high single dose of corn oil

Huber¹,

Grasl‐Kraupp²,

Stekel

et al. 1997

Archives of Toxicology

View full text Add to dashboard Cite

Oxidative stress is discussed as a possible hepatocarcinogenic mechanism of peroxisome proliferators (PP) in rodents and is suggested to result from the induction of peroxisomal beta-oxidation (PBOX) by PP. The induced PBOX is assumed to produce excessive H2O2 from the degradation of fatty acids, ultimately leading to oxidative stress and lipid peroxidation. In the present short term-study, we attempted to stimulate lipid peroxidation in male Wistar rats by (1) inducing PBOX enzymes with the peroxisome proliferator nafenopin at 90 mg/kg body weight per day in the diet for 10-11 days, and (2) by supplying the induced PBOX with an abundant amount of fatty acid as substrate, using a corn oil gavage at 20 ml/kg body weight. The corn-oil gavage alone, i.e. without preceding nafenopin treatment, enhanced liver triacylglycerol nine- to tenfold and hepatic lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS), was increased 50% compared with controls. Both observations were made after 18 h when the peak elevations occurred. Upon pretreatment with nafenopin, associated with a sevenfold induction of PBOX, the corn oil gavage however caused only a threefold maximal increase in hepatic triacylglycerol, also at the 18 h time-point; TBARS remained almost at control levels, as monitored at seven time points over 24-25 h. These results suggest that nafenopin reduces rather than enhances lipid peroxidation, despite the provision, in a short term study, of high doses of substrate to the induced enzyme system that is hypothetically causing oxidative stress in the liver.

show abstract

Chapter 19. Approaches to Drug Intervention in Atherosclerotic Disease

Newton¹,

Krause²

1986

Annual Reports in Medicinal Chemistry

View full text Add to dashboard Cite

Mechanisms of Action of Absorbable Hypolipidemic Drugs

Cited by 3 publications

References 31 publications

PPAR Agonists and Metabolic Syndrome: An Established Role?

PPAR Agonists and Metabolic Syndrome: An Established Role?

Inhibition instead of enhancement of lipid peroxidation by pretreatment with the carcinogenic peroxisome proliferator nafenopin in rat liver exposed to a high single dose of corn oil

Chapter 19. Approaches to Drug Intervention in Atherosclerotic Disease

Contact Info

Product

Resources

About