The effect of melatonin on oxidative stress and apoptosis in experimental diabetes mellitus-related ovarian injury

Naykı, Ümit; Önk, Didem; Balci, Gurhan; Naykı, Cenk; Onk, Alper; Çankaya, Murat; Kafa, Ayşe Hümeyra Taşkın; Kuzucu, Mehmet

doi:10.3109/09513590.2015.1126819

Cited by 12 publications

(27 citation statements)

References 39 publications

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“…Tresguerres' group also reported that melatonin reduced age-associated increases in HOMA-IR [131]. Similar studies suggest that melatonin reduces mitochondrial dysfunction [132], inhibits oxidative enzyme activity [133], decreases apoptosis [134], improves dyslipidaemia [135] and reduces diabetes-induced oxidative stress [135]. Together, these rodent studies strengthen the assertion that reductions in melatonin promote insulin resistance and hyperglycaemia, and that these conditions can be corrected with exogenous melatonin administration.…”

Section: The Pancreatic Response To Melatoninsupporting

confidence: 69%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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In mammals, the circadian timing system drives rhythms of physiology and behaviour, including the daily rhythms of feeding and activity. The timing system coordinates temporal variation in the biochemical landscape with changes in nutrient intake in order to optimise energy balance and maintain metabolic homeostasis. Circadian disruption (e.g. as a result of shift work or jet lag) can disturb this continuity and increase the risk of cardiometabolic disease. Obesity and metabolic disease can also disturb the timing and amplitude of the clock in multiple organ systems, further exacerbating disease progression. As our understanding of the synergy between the timing system and metabolism has grown, an interest has emerged in the development of novel clock-targeting pharmaceuticals or nutraceuticals for the treatment of metabolic dysfunction. Recently, the pineal hormone melatonin has received some attention as a potential chronotherapeutic drug for metabolic disease. Melatonin is well known for its sleep-promoting effects and putative activity as a chronobiotic drug, stimulating coordination of biochemical oscillations through targeting the internal timing system. Melatonin affects the insulin secretory activity of the pancreatic beta cell, hepatic glucose metabolism and insulin sensitivity. Individuals with type 2 diabetes mellitus have lower night-time serum melatonin levels and increased risk of comorbid sleep disturbances compared with healthy individuals. Further, reduced melatonin levels, and mutations and/or genetic polymorphisms of the melatonin receptors are associated with an increased risk of developing type 2 diabetes. Herein we review our understanding of molecular clock control of glucose homeostasis, detail the influence of circadian disruption on glucose metabolism in critical peripheral tissues, explore the contribution of melatonin signalling to the aetiology of type 2 diabetes, and discuss the pros and cons of melatonin chronopharmacotherapy in disease management.

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Section: The Pancreatic Response To Melatoninsupporting

confidence: 69%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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“…Both pathways end with the activation of caspase 3, leading to cell death [ 22 – 25 ]. In relation to the diabetic ovary, our results confirm previous observations that demonstrated activation of the intrinsic pathway through BAX as a consequence of hyperglycemia [ 2 , 9 , 13 – 18 , 26 ]. However, we observed the specific dynamics of apoptosis-related proteins, with the highest levels occurring at 15 and 20 days posttreatment in the granulose cells of antral follicles.…”

Section: Discussionsupporting

confidence: 91%

“…Several studies have shown an association between DM and female reproductive disturbances, including amenorrhea, early menopause onset and infertility [ 2 , 6 , 9 , 10 , 12 – 18 ]. These alterations have been related to the injurious effects of hyperglycemia through the overproduction of AGEs and ROS, which trigger the caspase 3 apoptosis pathway [ 2 , 4 , 6 , 13 , 16 ]. However, these studies analyzed the effects of DM at a single time point, without correlating follicular loss with the expression of apoptotic proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Then, all 20 mice (3 diabetics and 2 controls per day) were randomly euthanized at different time points (15, 20, 70 and 80 days posttreatment). These time points were selected to coincide with those described by several authors who have used STZ to induce DM [ 2 , 9 , 13 , 19 ]. At each time point, blood samples were collected to evaluate the glucose levels, and the ovaries were removed and weighed.…”

Section: Methodsmentioning

confidence: 99%

“…Chronically high glucose levels have deleterious effects on the structure and function of various organs [ 2 – 4 ]. Tissue damage has been related to the increased formation of advanced glycation end products (AGEs) [ 5 , 6 ] and the overproduction of reactive oxygen species (ROS) [ 2 , 5 ], which can cause oxidative stress, vascular endothelial cell damage and inflammatory cytokine production [ 3 , 7 , 8 ]. Among women with DM, menstrual complications, such as polymenorrhea, oligomenorrhea and amenorrhea followed by ovulation failure, have been described [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Long-term apoptosis-related protein expression in the diabetic mouse ovary

et al. 2018

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Emerging evidence has shown that oocytes from diabetic ovaries exhibit delayed maturation, mitochondrial dysfunction and meiotic defects, which are related increased apoptosis. The main objective of the present study was to analyze the apoptosis pathways activated during follicular loss at multiple time points in a diabetic mouse model. Twenty BALB/c mice were used in this study, and diabetes mellitus was induced by streptozotocin injection. Three diabetic and two control animals were sacrificed on days 15, 20, 70 and 80 posttreatment. The ovaries were then removed; one was used for follicular counting, TUNEL, immunohistochemistry and immunofluorescence, while the other was used for Western blot analysis. The proteins studied were BAX, BCL2, t-BID, FAS, FASL, active caspase 8, active caspase 9 and active caspase 3. Follicular apoptosis decreased over time, with the highest values observed at 15 days posttreatment. Granulosa cells were positive for active caspase 3, which showed constant expression levels at all time points. FAS, FASL, t-BID and active caspase 8 showed strong cytoplasmic immunostaining in the oocytes and granulosa cells of the diabetic mice, with significant increases observed at 15, 20 and 70 days posttreatment. BAX expression was slightly higher in the diabetic mouse ovaries than in the control ovaries at 15, 20 and 70 days posttreatment, whereas the highest active caspase 9 expression was at observed 20 days posttreatment. Low BCL2 protein levels were detected in the diabetic mouse ovaries at all time points. This study describes for the first time the behavior of apoptosis-related proteins in the diabetic mouse ovary and shows not only that the FAS/FASL pathway contributes to follicular loss but also that antral follicles are the most affected.

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