Agomelatine reduces circulating triacylglycerides and hepatic steatosis in fructose-treated rats

Veronesi, Vanessa Barbosa; Pioli, Mariana Rodrigues; Souza, Dailson Nogueira de; Teixeira, Caio Jordão; Murata, Gilson Masahiro; Santos-Silva, Junia Carolina; Hecht, Fernanda Ballerini; Vicente, Julia Modesto; Bordin, Silvana; Anhê, Gabriel Forato

doi:10.1016/j.biopha.2021.111807

Cited by 8 publications

(3 citation statements)

References 65 publications

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“…Population-based studies collected consistent evidence showing that nutritional habits, such as excessive consumption of artificially sweetened soft drinks, are associated with increased risk for NAFLD independently of body weight gain [ 5 , 6 , 7 ]. In experimental contexts, liver fat accumulation is induced in rodents exposed to liquid fructose or fructose-enriched diets [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats

et al. 2022

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Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC.

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Section: Introductionmentioning

confidence: 99%

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats

et al. 2022

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“…A 25 mg/mL agomelatine suspension was created by combining the powder with saline (0.9% NaCl) solution (1 mL/tablet). The amount of agomelatine was calculated to produce a dose of 40 mg/kg 20 …”

Section: Methodsmentioning

confidence: 99%

“…The amount of agomelatine was calculated to produce a dose of 40 mg/kg. 20 Based on earlier research demonstrating that agomelatine lowers corticosterone levels and neuronal/behavioural parameters in rats subjected to acute stress or high fat diet, this dosage of agomelatine was used. 18…”

Section: Drugs and The Rational Of Dose Selectionmentioning

confidence: 99%

Agomelatine alleviates steroid‐induced osteoporosis by targeting SIRT1/RANKL/FOXO1/OPG signalling in rats

El‐Mahroky,

Nageeb,

Hemead

et al. 2023

Clin Exp Pharma Physio

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One of the major contributors to secondary osteoporosis is long‐term glucocorticoid usage. Clinically used antidepressant agomelatine also has anti‐inflammatory properties. Our research aimed to inspect the probable defensive effect of agomelatine against steroid‐promoted osteoporosis. There were four groups of rats; group I had saline as a negative control; rats of group II had dexamethasone (0.6 mg/kg, s.c.), twice weekly for 12 weeks; rats of group III had agomelatine (40 mg/kg/day, orally), as a positive control, daily for 12 weeks; and rats of group IV had dexamethasone + agomelatine in the same previous doses combined for 12 weeks. Finally, biochemical as well as histopathological changes were evaluated and dexamethasone treatment caused osteoporosis, as evidenced by discontinuous thin cancellous bone trabeculae, minor fissures and fractures, irregular eroded endosteal surface with elevated alkaline phosphate, tartarate resistant acid phosphate (TRACP) and osteocalcin levels. Osteoprotegerin (OPG), calcium, and phosphorus levels decreased with disturbed receptor activator of nuclear factor κ B ligand (RANKL), forkhead box O1 (FOXO1), and silent information regulator 1 (SIRT1) protein expression. However, treatment with agomelatine restored the normal levels of biochemical parameters to a great extent, supported by SIRT activation with an improvement in histopathological changes. Here, we concluded that agomelatine ameliorates steroid‐induced osteoporosis through a SIRT1/RANKL/FOXO1/OPG‐dependent pathway.

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Antenatal corticosteroid therapy modulates hepatic AMPK phosphorylation and maternal lipid metabolism in early lactating rats

Hecht

Teixeira

Souza

et al. 2021

Biomedicine & Pharmacotherapy

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Agomelatine reduces circulating triacylglycerides and hepatic steatosis in fructose-treated rats

Cited by 8 publications

References 65 publications

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats

Agomelatine alleviates steroid‐induced osteoporosis by targeting SIRT1/RANKL/FOXO1/OPG signalling in rats

Antenatal corticosteroid therapy modulates hepatic AMPK phosphorylation and maternal lipid metabolism in early lactating rats

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