Fenofibrate A peroxisome proliferator activated receptor-α agonist treatment ameliorates Concanavalin A-induced hepatitis in rats

Mohamed, Doaa I.; Elmelegy, Ahmed Abdel Salam Mohamed; El-Aziz, Lubna F.A.; Kawy, Hala Salah Abdel; El-Samad, Abeer A. Abd; El-Kharashi, Omnyah A.

doi:10.1016/j.ejphar.2013.09.058

Cited by 18 publications

(14 citation statements)

References 25 publications

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“…Recently, a study [18 ]has found that TNF-α expression after weight loss only decreased in adipose tissue, not in hepatic tissue, but our study showed that TNF-α protein expression was increased in the liver and contributed partly to an increased TNF-α level in serum, whereas fenofibrate treatment obviously decreased TNF-α protein expression in the NAFLD mice. Mohamed et al [19] also reported that fenofibrate treatment significantly suppressed early inflammation and apoptosis of hepatocytes induced by concanavalin A, similar to our reports of fenofibrate treatment in NAFLD mice.…”

Section: Discussionsupporting

confidence: 80%

Fenofibrate Treatment Attenuated Chronic Endoplasmic Reticulum Stress in the Liver of Nonalcoholic Fatty Liver Disease Mice

Zhang

Lu²,

Shen

et al. 2015

Pharmacology

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Fenofibrate is widely used in clinical practice, but its influence on chronic endoplasmic reticulum (ER) stress induced by feeding a high-calorie and high-cholesterol diet (HCD) has still not been studied. We thus investigated its effects on the liver of the nonalcoholic fatty liver disease (NAFLD) mouse model. Male C57BL/6 mice fed an HCD for 3 months were treated with fenofibrate (HCD + FF, 40 mg/kg, once daily) via gavage for 4 weeks. Insulin sensitivity, serum lipid and inflammatory cytokines were measured. Liver tissues were procured for histological examination as well as analysis of hepatic triglyceride levels, distribution of inflammatory cytokines and genes involved in ER stress. Our results showed that chronic feeding of an HCD successfully induced an NAFLD model accompanied by inflammatory activation, apoptosis and severe ER stress in the liver. Fenofibrate administration significantly improved symptoms of NAFLD and decreased apoptosis, expression of inflammatory cytokines and genes involved in ER stress, such as inositol-requiring enzyme 1α (IRE1α), X-box binding protein 1 (XBP1) and JNK phosphorylation. Thus, our study suggests that fenofibrate protected against inflammatory injury and apoptosis, maybe alleviating ER stress through the IRE1α-XBP1-JNK pathway in the liver of NAFLD mice.

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Section: Discussionsupporting

confidence: 80%

Fenofibrate Treatment Attenuated Chronic Endoplasmic Reticulum Stress in the Liver of Nonalcoholic Fatty Liver Disease Mice

Zhang

Lu²,

Shen

et al. 2015

Pharmacology

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“…Interestingly, the group cotreated with both apocynin and α-LA showed a more pronounced hepatoprotective effect as compared to that treated with apocynin alone. Beside hepatotoxicity indices; histopathological examination revealed severe inflammatory cells infiltration as well as severe fibrosis in the portal area induced by ConA which is in accordance with previous studies (20,21). Remarkably, the combination of apocynin and α-LA preserved normal liver tissue architecture with few inflammatory cells infiltration.…”

Section: Discussionsupporting

confidence: 74%

The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4

Fayed

El-Naga

Akool

et al. 2018

DD&T

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“…As about one-fourth to one-third of blood cholesterol is carried by HDL, hence, low serum HDL levels caused by FF might result from the drug-induced hypocholesterolemia in normal mice. Although fibrate treatment improved liver function in patients with metabolic syndrome in clinic situation [49] and ameliorated concanavalin A-induced hepatitis in rats [50], FF can cause acute cholestatic hepatitis in patients [51–53]. In the present study, the daily supplementation with FF (130–150 mg/kg; about 30-fold higher than the human dose) induced hepatomegaly and increased ALT levels in normal and HCL mice.…”

Section: Discussionmentioning

confidence: 56%

Supplementation with the Extract of Schisandrae Fructus Pulp, Seed, or Their Combination Influences the Metabolism of Lipids and Glucose in Mice Fed with Normal and Hypercholesterolemic Diet

Wang

Pan

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Schisandrae Fructus (SF), which possesses five tastes: sweet (fruit skin), sour (pulp), bitter/pungent (seed core), and saltiness (all parts), can produce a wide spectrum of biological activities in the body. Here, we investigated the effects of the ethanolic extract of SF pulp, seed, or their combination (namely, EtSF-P, EtSF-S, or EtSF-P/S, resp.; collectively called EtSF) on the metabolism of lipids and glucose in normal diet- (ND-) and hypercholesterolemic diet- (HCLD-) fed mice. Supplementation with EtSF significantly reduced hepatic triglyceride and cholesterol levels by 18–47% in both ND- and HCLD-fed mice. EtSF supplementation reduced serum triglyceride levels (approximately 29%), whereas EtSF-P and EtSF-S/P elevated serum cholesterol (up to 26 and 44%, resp.) in HCLD-fed mice. Treatment with EtSF decreased hepatic glucose levels (by 9–44%) in both ND- and HCLD-fed mice. Supplementation with EtSF-S or EtSF-S/P (at 1 and 3%) increased biliary or fecal TC contents in HCLD-fed mice. However, supplementation with EtSF-S/P at 9% reduced biliary TC levels in HCLD-fed mice. EtSF-P or EtSF-S/P supplementation reduced serum alanine aminotransferase activity in HCLD-fed mice. The findings suggested that supplementation with EtSF lowered lipid and glucose accumulation in the liver and increased fecal cholesterol contents in mice. Dietary supplementation with EtSF-P or EtSF-S/P attenuated liver damage in HCLD-fed mice.

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Fenofibrate A peroxisome proliferator activated receptor-α agonist treatment ameliorates Concanavalin A-induced hepatitis in rats

Cited by 18 publications

References 25 publications

Fenofibrate Treatment Attenuated Chronic Endoplasmic Reticulum Stress in the Liver of Nonalcoholic Fatty Liver Disease Mice

Fenofibrate Treatment Attenuated Chronic Endoplasmic Reticulum Stress in the Liver of Nonalcoholic Fatty Liver Disease Mice

The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4

Supplementation with the Extract of Schisandrae Fructus Pulp, Seed, or Their Combination Influences the Metabolism of Lipids and Glucose in Mice Fed with Normal and Hypercholesterolemic Diet

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