The GLP-1 analog liraglutide attenuates acute liver injury in mice.

Autor: Milani L; Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil., Galindo CM; Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil., Turin de Oliveira NM; Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil., Corso CR; Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil., Adami ER; Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil., Stipp MC; Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil., Beltrame OC; Department of Veterinary Medicine, Federal University of Paraná, Curitiba, PR, Brazil., Acco A; Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address: aleacco@ufpr.br.
Jazyk: angličtina
Zdroj: Annals of hepatology [Ann Hepatol] 2019 Nov - Dec; Vol. 18 (6), pp. 918-928. Date of Electronic Publication: 2019 May 23.
DOI: 10.1016/j.aohep.2019.04.011
Abstrakt: Introduction and Objectives: Acute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective and curative potential of the glucagon-like peptide-1 analog liraglutide against carbon tetrachloride (CCl 4 )-induced hepatotoxicity.
Materials and Methods: Male Swiss mice were subjected to two protocols. The first protocol (Pretreatment) consisted of intraperitoneal (i.p.) treatment with liraglutide (0.057 and 0.118mgkg -1 ) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl 4 (5mgkg -1 , i.p.). The second protocol (Late treatment) began with an injection of 5% CCl 4 (5mgkg -1 , i.p.) and subsequent treatment with liraglutide (0.057mgkg -1 ) or vehicle (distilled water) for 1 day. In both protocols, 24h after the last administration, blood and bile were collected from anesthetized animals, followed by euthanasia and liver collection. Plasma and bile underwent biochemical analyses, and histological, oxidative stress, and metabolic parameters were evaluated in the liver.
Results: Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl 4 , decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl 4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter.
Conclusions: The present results demonstrated the hepatoprotective and therapeutic effects of liraglutide, which may be attributable to a decrease in liver oxidative stress and the preservation of metabolism. Liraglutide may have potential as a complementary therapy for acute liver injury.
(Copyright © 2019. Published by Elsevier España, S.L.U.)
Databáze: MEDLINE
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