Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice

Ozcan, Mete; Canpolat, Sinan; Bulmuş, Özgür; Ulker, Nazife; Tektemur, Ahmet; Tekin, Suat; Özcan, Sibel; Serhatlioğlu, İhsan; Kacar, Emine; Ayar, Ahmet; Keleştimur, Haluk

doi:10.1111/fcp.12413

Cited by 8 publications

(3 citation statements)

References 54 publications

(58 reference statements)

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“…The antidepressant mechanism of agomelatine action is not yet completely understood ( 6 , 7 , 40 – 42 ). Since molecular studies of the antiglycation/antioxidant properties of agomelatine have yet to be conducted, our study was the first to evaluate them comprehensively.…”

Section: Discussionmentioning

confidence: 99%

Agomelatine's antiglycoxidative action—In vitro and in silico research and systematic literature review

et al. 2023

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IntroductionAgomelatine is an atypical antidepressant drug enhancing norepinephrine and dopamine liberation; nevertheless, additional mechanisms are considered for the drug's pharmacological action. Since protein glycoxidation plays a crucial role in depression pathogenesis, agomelatine's impact on carbonyl/oxidative stress was the research purpose.MethodsReactive oxygen species scavenging (hydroxyl radical, hydrogen peroxide, and nitrogen oxide) and antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating assays) of agomelatine were marked. Agomelatine's antiglycoxidation properties were assayed in sugars (glucose, fructose, and galactose) and aldehydes- (glyoxal and methylglyoxal) glycated bovine serum albumin (BSA). Aminoguanidine and α-lipoic acid were used as standard glycation/oxidation inhibitors.ResultsAgomelatine did not show meaningful scavenging/antioxidant capacity vs. standards. Sugars/aldehydes increased glycation (↑kynurenine, ↑N-formylkynurenine, ↑dityrosine, ↑advanced glycation end products, and ↑β-amyloid) and oxidation (↑protein carbonyls and ↑advanced oxidation protein products) parameters in addition to BSA. Standards restored BSA baselines of glycation and oxidation markers, unlike agomelatine which sometimes even intensifies glycation above BSA + glycators levels. Molecular docking analysis of agomelatine in BSA demonstrated its very weak binding affinity.DiscussionAgomelatine's very low affinity to the BSA could proclaim non-specific bonding and simplify attachment of glycation factors. Thereby, the drug may stimulate brain adaptation to carbonyl/oxidative stress as the systematic review indicates. Moreover, the drug's active metabolites could exert an antiglycoxidative effect.

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Section: Discussionmentioning

confidence: 99%

Agomelatine's antiglycoxidative action—In vitro and in silico research and systematic literature review

et al. 2023

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“…In addition to the studies reporting that antidepressants might have antioxidant characteristics (Kirkova et al, ; Kumar, Garg, Gaur, & Kumar, ), there are also several other studies reporting that paroxetine and other antidepressants have pro‐oxidant characteristics and cause oxidative stress (Ademosun, Adebayo, & Oboh, ; Inkielewicz‐Stepniak, ). Agomelatine is considered as an antidepressant that has antioxidant characteristics (Ozcan et al, ; Yigitturk et al, ). Oxidative stress and ROS formation by spermatozoa might cause decreased motility, sperm damage, deformity and male infertility (Agarwal, Virk, Ong, & Plessis, ; Bansal & Bilaspuri, ; Iwasaki & Gagnon, ).…”

Section: Discussionmentioning

confidence: 99%

Kisspeptin and RF9 prevent paroxetine‐induced changes in some parameters of seminal vesicle fluid in the male rats

et al. 2020

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The aim of the study was to examine possible impacts of paroxetine and agomelatine on the levels of some components that constitute the seminal vesicle fluid. As a second purpose, it was also aimed to examine how possible negative effects induced by paroxetine on seminal vesicle fluid components were affected by kisspeptin and RF9 (an RFamide‐related peptide antagonist, RFRP). Forty‐two male rats, aged 21 days, divided into six groups; control, sham, paroxetine, agomelatine, paroxetine + kisspeptin and paroxetine + RF9. Paroxetine (3.6 mg/kg) and agomelatine (10 mg/kg) were administrated by oral gavage. Kisspeptin (1 nmol) and RF9 (20 nmol) were administered intracerebroventricular (i.c.v). The experiments were ended on post‐natal 120 days; fructose, vitamin E, sodium, potassium and magnesium levels were measured in seminal vesicle fluid. Fructose, vitamin E, magnesium and potassium levels were significantly decreased in seminal vesicle fluid from the rats treated with paroxetine but did not show significant differences following agomelatine administration. The co‐administration of kisspeptin or RF9 with paroxetine prevented the paroxetine‐induced negative effects on seminal vesicle fluid components. These results suggest that reduction in sperm fertilising ability caused by changes in seminal vesicle fluid can be seen in long‐term antidepressant use. RF‐9 and kisspeptin might have positive effects on long‐term antidepressant use‐induced infertility.

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“…Recently, it has been reported its anxiolytic/antidepressant effect in obese rats, maybe due to an amelioration of the high fat diet (HFD)-associated alterations [24]. Moreover, the capacity of agomelatine to prevent diabetes in a murine model has been explored [25]. However, a comprehensive study of the effects of agomelatine across the different organs involved would be necessary to consider its therapeutic value in these conditions.…”

Section: Introductionmentioning

confidence: 99%

The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome.

Diez-Echave,

Vezza,

Algieri

et al. 2024

Preprint

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Background and Purpose: Melatonin has shown beneficial effects on obesity, both in humans and experimental models, via regulating the altered circadian rhythm and thus ameliorating the gut dysbiosis associated with this metabolic condition. However, its clinical use is limited, mostly due to its short half-life. Agomelatine is an agonist of the melatonin receptors that could be used to manage obesity and offer a better profile than melatonin. Experimental Approach: Male C57BL/6 mice were fed a high fat diet and orally treated for five weeks with agomelatine, or melatonin or metformin, used as control drugs. Metabolic profile, inflammatory status, vascular dysfunction and intestinal microbiota composition were assessed. Key Results: Agomelatine lessened body weight gain, enhanced glucose and lipid metabolisms, and improved insulin resistance. It also reduced the obesity-associated inflammatory status and endothelial dysfunction, probably linked to its effect on gut dysbiosis, consisting of the restoration of bacterial populations with key functions, such as short chain fatty acid production. Conclusions and Implications: Agomelatine can be considered as a novel therapeutic tool for the management of human obesity and its associated comorbidities.

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Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice

Cited by 8 publications

References 54 publications

Agomelatine's antiglycoxidative action—In vitro and in silico research and systematic literature review

Agomelatine's antiglycoxidative action—In vitro and in silico research and systematic literature review

Kisspeptin and RF9 prevent paroxetine‐induced changes in some parameters of seminal vesicle fluid in the male rats

The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome.

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