Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats.

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats.

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Amygdala - and serum - neurotrophic factor levels depend on rearing condition in male rats.

Early life experiences could determine brain and behavioral development. Neurotrophic factors are likely to mediate the effects of the experience on brain structures and function. Brain-derived neurotrophic factor (BDNF) plays a central role in psychiatric disorders. To investigate the effects of early rearing condition on the amygdala - and serum - BDNF levels, we reared male Wistar rats from weaning (postnatal days 21) to adulthood (postnatal days 119) in three different rearing conditions: (1) enriched, (2) standard and (3) isolated. We found that long-term post-weaning environmental enrichment leads to lower amygdala - and serum - BDNF levels as well as lower brain weights. Grouped rearing in standard laboratory cages enhanced body weight. Thus, early rearing condition might play a crucial role in adult healthiness by predetermining individual BDNF profiles.

THE EFFECT OF TESTOSTERONE AND VOLUNTARY EXERCISE, ALONE OR TOGETHER, ON miRNA-126 EXPRESSION CHANGES IN HEART OF DIABETIC RATS.

METHODS: Ninety Wistar male rats were used in this study. Type 1 diabetes was induced by i.p injection of 50 mg/kg of streptozotocin in all animals. After 42 days of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, the heart of the rats has been removed and MicroRNA was extracted from the heart using miRCURYTM RNA isolation kit. RESULTS: Our results showed that either testosterone or exercise increased miRNA-126 expression levels in the heart of diabetic rats. Treatment of diabetic rats with testosterone and exercise at the same time had a synergistic effect on miRNA-126 levels in the heart. Furthermore, in castrated diabetes group, miRNA-126 levels were significantly decreased in heart, whereas either testosterone treatment or exercise training enhanced expression of this miRNA. Also, simultaneous treatment of castrated diabetic rats with testosterone and exercise had an additive effect on miRNA-126 expression levels. CONCLUSION: This study showed that testosterone and exercise promote an increase in the expression of miRNA-126 in the heart tissue and this may be related to cardiac angiogenesis. These results may indicate that testosterone and exercise can help to prevent progression of diabetic cardiomyopathy due to impaired angiogenesis in the heart.

Effects of crocin and voluntary exercise, alone or combined, on heart VEGF-A and HOMA-IR of HFD/STZ induced type 2 diabetic rats.

BACKGROUND: Hyperglycemia is the main risk factor for microvascular complications in type 2 diabetes. Crocin and voluntary exercise have anti-hyperglycemic effects in diabetes. In this research, we evaluated the effects of crocin and voluntary exercise alone or combined on glycemia control and heart level of VEGF-A. MATERIALS AND METHODS: Animals were divided into eight groups as: control (con), diabetes (Dia), crocin (Cro), voluntary exercise (Exe), crocin and voluntary exercise (Cro-Exe), diabetic-crocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by a high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p, 35 mg/kg). Animals received oral administration of crocin (50 mg/kg) or performed voluntary exercise alone or together for 8 weeks. Oral glucose tolerance test (OGTT) was performed on overnight fasted control, diabetic and treated rats after 8 weeks of treatment. Then, serum insulin and heart VEGF-A protein levels were measured. RESULTS: Crocin combined with voluntary exercise significantly decreased blood glucose levels (p < 0.001) and insulin resistance (HOMA-IR) (p < 0.001) compared to diabetic group. VEGF-A level was significantly (p < 0.01) lower in Dia group compared to control group. The combination of crocin and voluntary exercise significantly enhanced VEGF-A protein levels in Dia-Cro-Exe and Cro-Exe group compared to diabetic and control groups, respectively; p < 0.001 and p < 0.05. DISCUSSION: Crocin combined with voluntary exercise improved insulin resistance (HOMA-IR) and reduced glucose levels in diabetic rats. Since both crocin and voluntary exercise can increase VEGF-A protein expression in heart tissue, they probably are able to increase angiogenesis in diabetic animals.

Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats.

Background Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabetic-associated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats. Materials and methods Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically. Results Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats. Conclusion We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats.

Since some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the protective effects of garlic (Allium sativum) were investigated in the blood and heart of streptozotocin-induced diabetic rats. Twenty-eight male Wistar rats were randomly divided into four groups: control, garlic, diabetic, and diabetic+garlic. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (50 mg/kg) in male rats. Rats were fed with raw fresh garlic homogenate (250 mg/kg) six days a week by gavage for a period of 6 weeks. At the end of the 6th week blood samples and heart tissues were collected and used for determination of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and histological evaluation. Induction of diabetes increased MDA levels in blood and homogenates of heart. In diabetic rats treated with garlic, MDA levels decreased in blood and heart homogenates. Treatment of diabetic rats with garlic increased SOD, GPX and CAT in blood and heart homogenates. Histopathological finding of the myocardial tissue confirmed a protective role for garlic in diabetic rats. Thus, the present study reveals that garlic may effectively modulate antioxidants status in the blood and heart of streptozotocin induced-diabetic rats.

Does ghrelin level change after epileptic seizure in rats?

AIM: Epilepsy is one of the most common neurologic problems worldwide. A relationship between epilepsy and hormones has been demonstrated. This study was designed to investigate the effect of seizure on blood ghrelin level. METHODS: Twenty male Wistar rats were divided into two groups. The control group received saline and the pentylenetetrazole (PTZ) group received a single convulsive dose (50mg/kg) of PTZ. Thirty minutes later blood samples were collected and acylated and unacylated ghrelin levels in the plasma were assayed. RESULTS: Acylated or active form of ghrelin decreased significantly (p<0.05) after a PTZ-induced seizure, but the reduction of unacylated and total blood ghrelin levels failed to reach statistical significance. CONCLUSION: These findings may reflect that PTZ-induced epilepsy decreases AG of plasma.

Intracerebroventricular insulin improves spatial learning and memory in male Wistar rats.

As one of the most studied protein hormones, insulin as well as its receptor have been known to play key roles in a variety of important biological processes. Detection of insulin and its receptor in the central nervous system (CNS) has led to a rapidly growing interest in the central effects of insulin. Insulin and its receptor are located in the specific area of the CNS with a diversity of region-specific functions different from its direct carbohydrate homeostasis in the periphery. The high density of insulin/insulin receptor in brain areas such as the hippocampus and cerebral cortex have shown to play an important role in higher cognitive functions, suggesting that insulin might be involved in the modulation of memory. Previous studies have offered controversial results regarding the effects of insulin on various types of memory. The aim of the present study is to determine whether intracerebroventricular (ICV) administration of insulin improves the water maze performance of rats. The experimental groups had pretraining insulin infusion (2, 4, 8, 16, and 32 mu) into the third ventricle, and then they were compared with a sham (saline) group. Insulin treatment caused an enhancing effect on spatial memory in a dose-dependent manner. The low doses (2, 4, and 8 mu) of insulin had no significant effect on the water maze achievement of rats, whereas higher doses (16 and 32 mu) significantly improved the rats' performance. These results suggest that ICV administration of insulin may result in a dose-dependent improvement of memory function in rats.