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Farnesol attenuates oxidative stress and liver injury and modulates fatty acid synthase and acetyl-CoA carboxylase in high cholesterol-fed rats

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Abstract

Dyslipidemia is a risk factor for cardiovascular disease, steatohepatitis, and progression of liver disorders. This study investigated the protective effect of farnesol (FAR), a sesquiterpene alcohol, against liver injury in high cholesterol diet (HCD)-fed rats, and its modulatory effect on fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). HCD was supplemented for 10 weeks, and the rats were concurrently treated with FAR. Rats that received HCD exhibited significant elevation of serum cholesterol, triacylglycerols, LDL and vLDL cholesterol, CRP, and pro-inflammatory cytokines and increased values of the cardiovascular risk indices. Serum transaminases, ALP, LDH and CK-MB, and hepatic lipid peroxidation (LPO), cholesterol, and triacylglycerols were increased in HCD-fed rats. Treatment with FAR greatly ameliorated dyslipidemia and liver function, reduced inflammatory mediators, LPO, and hepatic lipid infiltration and enhanced anti-oxidant defenses. FAR suppressed hepatic FAS, ACC, and SREPB-1c mRNA abundance and FAS activity in HDC-fed rats. In addition, molecular docking simulations pinpointed the binding modes of FAR to the active pocket residues of FAS and ACC. In conclusion, FAR possesses a strong anti-hyperlipidemic/anti-hypercholesterolemic activity mediated through its ability to modulate hepatic FAS, ACC, and SREPB-1c. FAR prevented oxidative stress, inflammation, and liver injury induced by HCD. Thus, FAR may represent a promising lipid-lowering agent that can protect against dyslipidemia and its linked metabolic deregulations.

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Funding

The authors extend their appreciation to the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University for supporting this research through the Fast-track Research Funding Program.

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Authors and Affiliations

  1. Department of Medical Analysis, Princess Aisha Bint Al-Hussein Faculty of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma’an, Jordan

    Mohammad H. Abukhalil & Sultan A. M. Saghir

  2. Department of Biology, Faculty of Science, Al-Hussein Bin Talal University, Ma’an, Jordan

    Mohammad H. Abukhalil

  3. Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef, Egypt

    Omnia E. Hussein & Ayman M. Mahmoud

  4. Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

    May Bin-Jumah

  5. Department of Biology, College of Science, Jouf University, Sakakah, Saudi Arabia

    Mousa O. Germoush, Hassan A. Elgebaly & Nermeen M. Mosa

  6. College of Applied Medical Sciences, Jouf University, Sakakah, Saudi Arabia

    Ismail Hamad

  7. Biochemistry Department, Bahri University, Khartoum, Sudan

    Ismail Hamad

  8. College of Medicine, Jouf University, Sakakah, Saudi Arabia

    Moath M. Qarmush

  9. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University-Assiut Branch, Cairo, Egypt

    Emad M. Hassanein

  10. Chemistry Department, Faculty of Science, Beni-Suef University, Beni Suef, Egypt

    Emadeldin M. Kamel

  11. Institute for Diabetes and Obesity, Helmholtz Center Munich, Neuherberg, Germany

    Rene Hernandez-Bautista

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  1. Mohammad H. Abukhalil
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  2. Omnia E. Hussein
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  13. Ayman M. Mahmoud
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Correspondence to Ayman M. Mahmoud.

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Mohammad H. Abukhalil and Omnia E. Hussein contributed as first authors.

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Abukhalil, M.H., Hussein, O.E., Bin-Jumah, M. et al. Farnesol attenuates oxidative stress and liver injury and modulates fatty acid synthase and acetyl-CoA carboxylase in high cholesterol-fed rats. Environ Sci Pollut Res 27, 30118–30132 (2020). https://doi.org/10.1007/s11356-020-09296-w

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