Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein

0467424 - FGÚ 2017 RIV CZ eng J - Journal Article
Škop, V. - Trnovská, J. - Oliyarnyk, O. - Marková, I. - Malínská, H. - Kazdová, L. - Zídek, Václav - Landa, Vladimír - Mlejnek, Petr - Šimáková, Miroslava - Kůdela, M. - Pravenec, Michal - Šilhavý, Jan
Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein.
Physiological Research. Roč. 65, č. 6 (2016), s. 891-899. ISSN 0862-8408. E-ISSN 1802-9973
R&D Projects: GA MZd(CZ) NT14325
Institutional support: RVO:67985823
Keywords : fenofibrate * rosuvastatin * C-reactive protein * transgenic * spontaneously hypertensive rat * inflammation * hepatotoxic
Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition
Impact factor: 1.461, year: 2016

Dyslipidemia and inflammation play an important role in the pathogenesis of cardiovascular and liver disease. Fenofibrate has a well-known efficacy to reduce cholesterol and triglycerides. Combination with statins can ameliorate hypolipidemic and antiinflammatory effects of fibrates. In the current study, we tested the anti-inflammatory and metabolic effects of fenofibrate alone and in combination with rosuvastatin in a model of inflammation and metabolic syndrome, using spontaneously hypertensive rats expressing the human C-reactive protein transgene (SHR-CRP transgenic rats). SHR-CRP rats treated with fenofibrate alone (100 mg/kg body weight) or in combination with rosuvastatin (20 mg/kg body weight) vs. SHR-CRP untreated controls showed increased levels of proinflammatory marker IL6, increased concentrations of ALT, AST and ALP, increased oxidative stress in the liver and necrotic changes of the liver. In addition, SHR-CRP rats treated with fenofibrate, or with fenofibrate combined with rosuvastatin vs. untreated controls, exhibited increased serum triglycerides and reduced HDL cholesterol, as well as reduced hepatic triglyceride, cholesterol and glycogen concentrations. These findings suggest that in the presence of high levels of human CRP, fenofibrate can induce liver damage even in combination with rosuvastatin. Accordingly, these results caution against the possible hepatotoxic effects of fenofibrate in patients with high levels of CRP.
Permanent Link: http://hdl.handle.net/11104/0265527