The Fenofibrate Effect on Genotoxicity in Brain and Liver and on the Expression of Genes Regulating Fatty Acids Metabolism of Mice

Khorolskaya, Victoria G.; Gureev, Artem P.; Shaforostova, Ekaterina A.; Laver, D A; Popov, Vasily N.

doi:10.1134/s1990750820010084

Cited by 4 publications

(2 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the rate of PCR product accumulation would be inversely proportional to the number of damaged DNA molecules [ 55 ]. Measurement of damage number was carried out in the six long fragments of mtDNA (NC_005089.1) [ 56 ]. In this research we used mtDNA fragments, which were not duplicated in the nuclear genome.…”

Section: Methodsmentioning

confidence: 99%

Age-Related Decline in Nrf2/ARE Signaling Is Associated with the Mitochondrial DNA Damage and Cognitive Impairments

Gureev

Khorolskaya

Sadovnikova

et al. 2022

IJMS

View full text Add to dashboard Cite

In this research, we compared the cognitive parameters of 2-, 7-, and 15-month-old mice, changes in mitochondrial DNA (mtDNA) integrity and expression of genes involved in the nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. We showed an age-related decrease in the Nfe2l2 expression in the cerebral cortex, not in the hippocampus. At the same time, we find an increase in the mtDNA copy number in the cerebral cortex, despite the lack of an increase in gene expression, which is involved in the mitochondrial biogenesis regulation. We suppose that increase in mtDNA content is associated with mitophagy downregulation. We supposed that mitophagy downregulation may be associated with an age-related increase in the mtDNA damage. In the hippocampus, we found a decrease in the Bdnf expression, which is involved in the pathways, which play an essential role in regulating long-term memory formation. We showed a deficit of working and reference memory in 15-month-old-mice in the water Morris maze, and a decrease in the exploratory behavior in the open field test. Cognitive impairments in 15-month-old mice correlated with a decrease in Bdnf expression in the hippocampus, Nfe2l2 expression, and an increase in the number of mtDNA damage in the cerebral cortex. Thus, these signaling pathways may be perspective targets for pharmacological intervention to maintain mitochondrial quality control, neuronal plasticity, and prevent the development of age-related cognitive impairment.

show abstract

Section: Methodsmentioning

confidence: 99%

Age-Related Decline in Nrf2/ARE Signaling Is Associated with the Mitochondrial DNA Damage and Cognitive Impairments

Gureev

Khorolskaya

Sadovnikova

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Fenofibrate promotes fatty acid oxidation and demonstrates antioxidant and anti-inflammatory properties (Mahmoudi et al, 2022). Unfortunately, it also has some adverse effects like weight loss, enhance triglyceride content in the liver, and causes hepatic toxicity (Khorolskaya et al, 2020;Mahmoudi et al, 2022). Therefore, alternative herbal ingredients which have the same properties and protective to the liver are needed to be explored.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Autophagy and Mitochondrial Dynamics Gene Expression by Turmeric and Mangosteen Peel Extract

Jasaputra

Gunadi

Sutiono

et al. 2023

J.Ilm.Kedokt. Wijaya Kusuma

View full text Add to dashboard Cite

High fat diet (HFD) induces oxidative stress and mitochondrial dysfunction which culminates in fatty liver disease. Autophagy and mitochondrial dynamics are affected by HFD. Turmeric and mangosteen have potential roles as antioxidants and regulators of mitochondrial function in the liver. The study aims to examine the effect of turmeric and mangosteen peel extract on autophagy and mitochondrial dynamics in the liver after HFD induction. Five groups of animals (n=5) as used: negative control, positive control (HFD), turmeric (HFD + 270 mg/kg BW turmeric extract), mangosteen (HFD + mangosteen 270 mg/kg BW peel extract), and fenofibrate (HFD + 15 mg/kg BW fenofibrate). HFD was given for 7 weeks, continued by another 7 weeks plus treatment. Liver sections were extracted to conduct semi-quantitative PCR. Autophagy (LC3, p62), mitophagy (Pink1, Parkin, Bnip3), mitochondrial fission (Drp1, Fis1), and mitochondrial fusion (Opa1, Mfn1, Mfn2) gene expression were measured. LC3 (p=0.048), p62 (p=0.043), Pink1 (p=0.012), Bnip3 (p=0.010), Mfn1 (p=0.015), and Mfn2 (p=0.035) gene expressions were differed significantly, while Parkin (p=0.098) Drp1 (p=0.962), Fis1 (p=0.570), and Opa1 (p=0.055) gene expressions did not differ between groups. Both turmeric and mangosteen peel extract have positive effects by activating autophagy, mitophagy, and mitochondrial fusion in rat liver induced by HFD.

show abstract

Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models

et al. 2022

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is initiated by excessive fat buildup in the liver, affecting around 35% of the world population. Various circumstances contribute to the initiation and progression of NAFLD, and it encompasses a wide range of disorders, from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Although several treatments have been proposed, there is no definitive cure for NAFLD. In recent decades, several medications related to other metabolic disorders have been evaluated in preclinical studies and in clinical trials due to the correlation of NAFLD with other metabolic diseases. Fenofibrate is a fibrate drug approved for dyslipidemia that could be used for modulation of hepatic fat accumulation, targeting peroxisome proliferator-activator receptors, and de novo lipogenesis. This drug offers potential therapeutic efficacy for NAFLD due to its capacity to decrease the accumulation of hepatic lipids, as well as its antioxidant, anti-inflammatory, and antifibrotic properties. To better elucidate the pathophysiological processes underlying NAFLD, as well as to test therapeutic agents/interventions, experimental animal models have been extensively used. In this article, we first reviewed experimental animal models that have been used to evaluate the protective effects of fenofibrate on NAFLD/NASH. Next, we investigated the impact of fenofibrate on the hepatic microcirculation in NAFLD and then summarized the beneficial effects of fenofibrate, as compared to other drugs, for the treatment of NAFLD. Lastly, we discuss possible adverse side effects of fenofibrate on the liver.

show abstract

The Fenofibrate Effect on Genotoxicity in Brain and Liver and on the Expression of Genes Regulating Fatty Acids Metabolism of Mice

Cited by 4 publications

References 28 publications

Age-Related Decline in Nrf2/ARE Signaling Is Associated with the Mitochondrial DNA Damage and Cognitive Impairments

Age-Related Decline in Nrf2/ARE Signaling Is Associated with the Mitochondrial DNA Damage and Cognitive Impairments

Modulation of Autophagy and Mitochondrial Dynamics Gene Expression by Turmeric and Mangosteen Peel Extract

Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models

Contact Info

Product

Resources

About