The GLP-1 analog liraglutide attenuates acute liver injury in mice
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 (CCl4)-induced hepatotoxicity. Male Swiss mice were subjected to two...
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| Published in: | Annals of hepatology Vol. 18; no. 6; pp. 918 - 928 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Mexico
Elsevier España, S.L.U
01.11.2019
Elsevier |
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| ISSN: | 1665-2681, 2659-5982 |
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| Abstract | 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 (CCl4)-induced hepatotoxicity.
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% CCl4 (5mgkg−1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (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.
Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter.
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. |
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| AbstractList | 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 (CCl4)-induced hepatotoxicity.
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% CCl4 (5mgkg−1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (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.
Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter.
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. 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 (CCl4)-induced hepatotoxicity.INTRODUCTION AND OBJECTIVESAcute 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 (CCl4)-induced hepatotoxicity.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% CCl4 (5mgkg-1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (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.MATERIALS AND METHODSMale 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% CCl4 (5mgkg-1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (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.Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter.RESULTSBoth liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter.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.CONCLUSIONSThe 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. AbstractIntroduction and objectivesAcute 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 methodsMale Swiss mice were subjected to two protocols. The first protocol (Pretreatment) consisted of intraperitoneal (i.p.) treatment with liraglutide (0.057 and 0.118 mg kg −1) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl 4 (5 mg kg −1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl 4 (5 mg kg −1, i.p.) and subsequent treatment with liraglutide (0.057 mg kg −1) or vehicle (distilled water) for 1 day. In both protocols, 24 h 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. ResultsBoth 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. ConclusionsThe 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. 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 )-induced hepatotoxicity. 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 ) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl (5mgkg , i.p.). The second protocol (Late treatment) began with an injection of 5% CCl (5mgkg , i.p.) and subsequent treatment with liraglutide (0.057mgkg ) 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. Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl , decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl tended to reduce bile lipid excretion, but liraglutide did not influence this parameter. 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. 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 (CCl4)-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 0.118 mg kg−1) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl4 (5 mg kg−1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (5 mg kg−1, i.p.) and subsequent treatment with liraglutide (0.057 mg kg−1) or vehicle (distilled water) for 1 day. In both protocols, 24 h 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 CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 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. |
| Author | Galindo, Claudia M. Milani, Letícia Corso, Claudia Rita Acco, Alexandra Adami, Eliana Rezende Stipp, Maria Carolina Beltrame, Olair Carlos Turin de Oliveira, Natalia Mulinari |
| Author_xml | – sequence: 1 givenname: Letícia surname: Milani fullname: Milani, Letícia organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 2 givenname: Claudia M. surname: Galindo fullname: Galindo, Claudia M. organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 3 givenname: Natalia Mulinari surname: Turin de Oliveira fullname: Turin de Oliveira, Natalia Mulinari organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 4 givenname: Claudia Rita surname: Corso fullname: Corso, Claudia Rita organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 5 givenname: Eliana Rezende surname: Adami fullname: Adami, Eliana Rezende organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 6 givenname: Maria Carolina surname: Stipp fullname: Stipp, Maria Carolina organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 7 givenname: Olair Carlos surname: Beltrame fullname: Beltrame, Olair Carlos organization: Department of Veterinary Medicine, Federal University of Paraná, Curitiba, PR, Brazil – sequence: 8 givenname: Alexandra surname: Acco fullname: Acco, Alexandra email: aleacco@ufpr.br organization: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31151874$$D View this record in MEDLINE/PubMed |
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| Keywords | Drug induced liver injury Incretin Oxidative stress Hepatotoxicity CCl4 CCl 4 CCl |
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| Snippet | Acute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective and curative potential of the... AbstractIntroduction and objectivesAcute liver injury is a current health problem with few effective treatments. The present study investigated the... Introduction and objectives: Acute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective... |
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| SubjectTerms | CCl4 Drug induced liver injury Gastroenterology and Hepatology Hepatotoxicity Incretin Oxidative stress |
| Title | The GLP-1 analog liraglutide attenuates acute liver injury in mice |
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