scholarly journals Hepatotoxic Effects of Fenofibrate in Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

2016 ◽  
pp. 891-899 ◽  
Author(s):  
V. ŠKOP ◽  
J. TRNOVSKÁ ◽  
O. OLIYARNYK ◽  
I. MARKOVÁ ◽  
H. MALÍNSKÁ ◽  
...  

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 anti-inflammatory 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.

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S26-S26
Author(s):  
J Neckar ◽  
F Papousek ◽  
V Farkasova ◽  
T Ravingerova ◽  
M Vecka ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150924 ◽  
Author(s):  
Hana Malínská ◽  
Olena Oliyarnyk ◽  
Vojtěch Škop ◽  
Jan Šilhavý ◽  
Vladimír Landa ◽  
...  

2018 ◽  
pp. 851-856
Author(s):  
J. ŠILHAVÝ ◽  
P. MLEJNEK ◽  
M. ŠIMÁKOVÁ ◽  
I. VANĚČKOVÁ ◽  
M. BEHULIAK ◽  
...  

Telmisartan is an angiotensin receptor blocker (ARB) and a selective peroxisome proliferator activated receptor gamma (PPARG) modulator. Recently, we tested metabolic effects of telmisartan (5 mg/kg body weight) in spontaneously hypertensive rats (SHR) fed a diet containing 60 % fructose, a widely used model of the metabolic syndrome. Surprisingly, we observed acute toxic effects of telmisartan. Rats lost body weight rapidly and died within 2 to 3 weeks due to bleeding into the upper gastrointestinal tract. SHR fed a high fructose diet and treated with telmisartan exhibited rapid decrease in blood pressure when compared to the SHR fed a high fructose diet and treated with valsartan. Concentrations of both unconjugated telmisartan and telmisartan glucuronide in the liver of SHR rats fed a high fructose diet were approximately 4 fold higher when compared to Brown Norway (BN) rats fed the same diet. Plasma concentrations of unconjugated telmisartan in the SHR were about 5 fold higher when compared to BN rats while plasma levels of telmisartan glucuronide were similar between the strains. Testing of other rat strains, diets, and the ARB valsartan showed that toxic effects of telmisartan in combination with high fructose diet are specific for the SHR. These results are consistent with the possibility that in some circumstances, SHR are predisposed to telmisartan toxicity possibly because of a genetically determined disturbance in telmisartan metabolism.


2021 ◽  
Vol 5 (1) ◽  
pp. 40
Author(s):  
Livia Kurniati Saputra ◽  
Dian Novita Chandra ◽  
Ninik Mudjihartini

Low grade inflammation has been recognized of being involved in the pathogenesis of chronic disease pandemic. Individual lifestyle plays a major role in the development of low grade inflammation. Sedentary workers are at risk of low grade inflammation due to the nature of their work. Dietary habit also contributes to inflammatory status in the body. Dietary fiber intake indirectly affects the immune system. It has been hypothesized that fiber has anti-inflammatory effects, both body weight-related and body weight-unrelated This review will focus more on body weight-unrelated anti-inflammatory effect of fiber, especially through fiber’s fermentation metabolites, the short chain fatty acid (SCFA). Its anti-inflammatory effect can be seen by monitoring a biomarker of inflammation in the body, the high sensitivity C-reactive protein (hsCRP). This review’s objective is to cover the mechanisms and role of dietary fiber intake on serum hsCRP level as a marker of low grade inflammation on sedentary workers. 


1985 ◽  
Vol 69 (5) ◽  
pp. 511-515 ◽  
Author(s):  
P. J. O. Manhem ◽  
S. A. Clark ◽  
W. B. Brown ◽  
G. D. Murray ◽  
J. I. S. Robertson

1. Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. 2. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. 3. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. 4. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. 5. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. 6. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. 7. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. 8. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. 9. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.


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