[Endogenous hypertriglyceridemia].

At present, it is very difficult, if not impossible, to draw reliable conclusions about the long-term risks of lipid lowering therapy. Many so-called "long-term" trials only cover a few years of treatment, comparative studies versus placebo are very rare and the notification of acute events in the context of pharmacovigilance does not provide information about the long-term risk. However, analysis of large scale primary or secondary prevention trials, the Lipid Research Clinics study with cholestyramine, the Helsinki cardiological study with gemfibrozil, the Coronary Drug Project with clofibrate and nicotinic acid, has not shown any significant differences between the treatment and control groups, in particular with regards to the prevalence of malignant disease. These reassuring observations contradict those of the WHO study with clofibrate: a significant increase in the incidence of cancer, especially gastrointestinal, is observed in the treatment group. Therefore, despite the absence of confirmed long-term clinical or biological adverse effects of lipid lowering drugs (apart from the WHO clofibrate study), the physician must remain vigilant, especially as the long-term risks are difficult to assess.

Clofibrate↗

PubMed1991

Peroxisome proliferation and oxidative stress mediated by activated oxygen species in plant peroxisomes.

The existence of a relationship between clofibrate-induced peroxisome proliferation and oxidative stress mediated by activated oxygen species was studied in intact peroxisomes purified from Pisum sativum L. plants. Incubation of leaves with 1 mM clofibrate produced a remarkable increase in the peroxisomal activity of acyl-CoA oxidase and, to a lesser extent, of xanthine oxidase, whereas there was a nearly complete loss of catalase activity and a decrease in Mn-superoxide dismutase. Ultrastructural studies of intact leaves showed that clofibrate induced a five- and twofold proliferation of the peroxisomal and mitochondrial populations, respectively, in comparison with those in control leaves. Prolonged incubation with clofibrate produced considerable alterations in the ultrastructure of cells. In peroxisomal membranes, the NADH-induced generation of O2- radicals, as well as the lipid peroxidation of membranes, increased as a result of treatment of plants with clofibrate. In intact peroxisomes treated with this hypolipidemic drug, the H2O2 concentration was higher than in peroxisomes from control plants. These results demonstrate that clofibrate stimulates the production of activated oxygen species (O2- and H2O2) inside peroxisomes, as well as the lipid peroxidation of peroxisomal membranes. This effect is concomitant with a decrease of catalase and Mn-SOD activities, the main peroxisomal enzymatic defenses against H2O2 and O2-, and indicates that in the toxicity of clofibrate, at the level of peroxisomes, an oxidative stress mechanism mediated by activated oxygen species is involved.

Clofibrate↗