Melatonin improves hyperglycemia induced damages in rat brain

Gurel-Gokmen, Begüm; Ipekci, Hazal; Oktay, Şule; Alev, Burçin; Üstündağ, Ünsal Veli; Ak, Esin; Akakın, Dilek; Şener, Göksel; Emekli-Alturfan, Ebru; Yarat, Ayşen; Tunalı-Akbay, Tuğba

doi:10.1002/dmrr.3060

Cited by 15 publications

(12 citation statements)

References 78 publications

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“…Treatment with MLT significantly ameliorated hyperglycemia and the reduction of insulin levels, blocked the glycosylation of hemoglobin and improved insulin resistance in T2DM rats. These results corroborate the improvement of hyperglycemia by MLT treatment in several experimental models [ 3 , 34 , 35 ]. These findings agree with the ability of MLT to reverse the reduction of GLUT4 gene expression, glucose intolerance and insulin resistance, and augmented gluconeogenesis in MLT-deficient pinealectomized rats [ 36 , 37 ].…”

Section: Discussionsupporting

confidence: 88%

“…The Framingham study showed that diabetic men and women were, respectively, two and five times more likely to develop heart problems than nondiabetic subjects [ 2 ]. T2DM is a metabolic disorder characterized by increased resistance to insulin in glucose-sensitive tissues and dyslipidemia leading to hyperglycemia, prolonged inflammation, and oxidative stress [ 3 ]. At the advanced stage, diabetic cardiomyopathy (DCM) clinically presents as heart failure in T1DM and T2DM [ 4 ]; however, the early events during the development of T2DM-induced organ injury are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

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Melatonin protects the heart and pancreas by improving glucose homeostasis, oxidative stress, inflammation and apoptosis in T2DM-induced rats

Abdulwahab

El-Missiry

Shabana

et al. 2021

Heliyon

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Cardiomyopathy and pancreatic injury are health issues associated with type 2 diabetes mellitus (T2DM) and are characterized by elevated oxidative stress, inflammation and apoptosis. Melatonin (MLT) is a hormone with multifunctional antioxidant activity. The protective effects of MLT on the heart and pancreas during the early development of diabetic cardiomyopathy and pancreatic injury were investigated in male Wistar rats with T2DM. MLT (10 mg/kg) was administered daily by gavage for 15 days after diabetic induction. Treatment of diabetic rats with MLT significantly normalized the levels of serum glucose, HbA1-c, and the lipid profile and improved the insulin levels and insulin resistance compared with diabetic rats, affirming its antidiabetic effect. MLT significantly prevented the development of oxidative stress and sustained the levels of glutathione and glutathione peroxidase activity in the heart and pancreas of diabetic animals, indicating its antioxidant capacity. Additionally, MLT prevented the increase in proinflammatory cytokines and expression of Bax, caspase-3 and P53. Furthermore, MLT enhanced the anti-inflammatory cytokine IL-10 and antiapoptotic protein Bcl-2. MLT controlled the levels of troponin T and creatine kinase-MB and lactate dehydrogenase activity, indicating its anti-inflammatory and antiapoptotic effects. Histological examinations confirmed the protective effects of MLT on T2DM-induced injury in the myocardium, pancreas and islets of Langerhans. In conclusion, the protective effects of melatonin on the heart and pancreas during the early development of T2DM are attributed to its antihyperglycemic, antilipidemic and antioxidant influences as well as its remarkable anti-inflammatory and antiapoptotic properties.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Melatonin protects the heart and pancreas by improving glucose homeostasis, oxidative stress, inflammation and apoptosis in T2DM-induced rats

Abdulwahab

El-Missiry

Shabana

et al. 2021

Heliyon

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“…The high concentrations of MLT in mitochondria provides further evidence of its role in anti-apoptotic and anti-oxidative stress (Reiter et al, 2016). Indeed, MLT has been shown to improve the glycemic state by upregulating GSH (Gurel-Gokmen et al, 2018). MLT levels in blood is lower in diabetic patients compared to healthy individuals (Cipolla-Neto et al, 2014;Reutrakul et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Melatonin Inhibits Glucose-Induced Apoptosis in Osteoblastic Cell Line Through PERK-eIF2α-ATF4 Pathway

Zhou

Tao

et al. 2020

Front. Pharmacol.

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Osteoporosis is a common disease resulting in deteriorated microarchitecture and decreased bone mass. In type 2 diabetes patients, the incidence of osteoporosis is significantly higher accompanied by increased apoptosis of osteoblasts. In this study, using the osteoblastic cell line MC3T3-E1, we show that high glucose reduces cell viability and induces apoptosis. Also, high glucose leads to endoplasmic reticulum (ER) stress (ERS) via an increase in calcium flux and upregulation of the ER chaperone binding immunoglobulin protein (BiP). Moreover, it induces post-translational activation of eukaryotic initiation factor 2 alpha (eIF2α) which functions downstream of PKR-like ER kinase (PERK). This subsequently leads to post-translational activation of the transcription factor 4 (ATF4) and upregulation of C/EBP-homologous protein (CHOP) which is an ER stress-induced regulator of apoptosis, as well as downstream effectors DNAJC3, HYOU1, and CALR. Interestingly, melatonin treatment significantly alleviates the high-glucose induced changes in cell growth, apoptosis, and calcium influx by inhibiting the PERK-eIF2α-ATF4-CHOP signaling pathway. Additionally, the MC3T3-E1 cells engineered to express a phosphodead eIF2α mutant did not show high glucose induced ER stress, confirming that melatonin protects osteoblasts against high-glucose induced changes by decreasing ER-stress induced apoptosis by impacting the PERK-eIF2α-ATF4-CHOP signaling pathway. The protective of melatonin against high glucose-induced ER stress and apoptosis was attenuated when the cells were pre-treated with a melatonin receptor antagonist, indicating that the effect of melatonin was mediated via the melatonin receptors in this context. These findings lay the provide mechanistic insights of melatonin’s protective action on osteoblasts and will be potentially be useful in ongoing pre-clinical and clinical studies to evaluate melatonin as a therapeutic option for diabetic osteoporosis.

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“…In general, antioxidants stabilize cell membranes (particularly, neuronal membranes) by counteracting lipid peroxidation . Antioxidant substances are plant extracts such as chard, spirulina platensis, resveratrol, cinnamon, grape seed, melatonin, quercetin, and others. All these antioxidants have proved their beneficial protective role against tissues, lipid peroxidation, and oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

The effects of vitamins and selenium mixture against brain tissue induced byd‐galactosamine

Tunalı

Çatal

Bolkent

et al. 2019

J Biochem & Molecular Tox

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Brain damage is a major complication of fulminant hepatic failure. d‐Galactosamine (d‐GalN)‐induced liver toxicity causes damage to brain. The effects of vitamins and selenium mixture against d‐GalN stimulated brain injury were investigated in this study. Sprague‐Dawley female rats aged 2.0‐2.5 months were used for the study. The rats were divided into four categories. A 0.9% NaCl solution was intraperitoneally given to the experimental rats in the first group. Using gavage technique, the second group of animals were subjected to a formulation consisting of 100 mg·kg−1·day−1 vitamin C, 15 mg·kg−1·day−1 of β‐carotene, 100 mg·kg−1·day−1 of α‐tocopherol in addition to 0.2 mg·kg−1·day−1 of sodium selenate for 3 days. The third group was given a single dose of d‐GalN hydrochloride at the concentration of 500 mg·kg−1 through a saline injection. The final group was given similar concentrations of both the antioxidant combination and d‐GalN. Tissue samples were collected under ether anesthesia. The rats treated with d‐GalN showed brain damage; increased myeloperoxidase, catalase, glutathione peroxidase, glutathione‐S‐transferase, lactate dehydrogenase, and superoxide dismutase activities; and decreased glutathione levels. Treatment with vitamins and selenium combination resulted in alleviation of these alterations in the rats. These findings suggest that administration of the vitamins and selenium combination suppresses oxidative stress and protects brain cells from injury induced by d‐GalN.

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Melatonin improves hyperglycemia induced damages in rat brain

Abstract: Addition of melatonin to the insulin treatment did not change the effects of insulin, but the detailed role of melatonin alone in the treatment of diabetes merits further experimental and clinical investigation.

Cited by 15 publications

References 78 publications

Melatonin protects the heart and pancreas by improving glucose homeostasis, oxidative stress, inflammation and apoptosis in T2DM-induced rats

Melatonin protects the heart and pancreas by improving glucose homeostasis, oxidative stress, inflammation and apoptosis in T2DM-induced rats

Melatonin Inhibits Glucose-Induced Apoptosis in Osteoblastic Cell Line Through PERK-eIF2α-ATF4 Pathway

The effects of vitamins and selenium mixture against brain tissue induced byd‐galactosamine

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