Modulatory effect of tropisetron in the liver of streptozotocin-induced diabetes in rats: biochemical and histological evidence.

Objectives There is an association between diabetes and liver disorders. Oxidative stress plays a crucial role in the pathology of hepatic abnormalities in diabetes. In this study, the effect of Tropisetron on the oxidative damage and histological alterations in the liver of type 1 diabetes mellitus (DM) were evaluated. Methods Thiry-five male Wistar rats were randomly divided into five experimental groups (n = 7): control (C), tropisetron (T), diabetes (D), diabetes + tropisetron (D + T) and diabetes + glibenclamide (D + G). A single injection of streptozotocin (STZ, 50 mg/kg; i.p) was used to induce diabetes. Tropisetron (3 mg/kg; i.p), as a 5-HT3 receptor antagonist and glibenclamide (1 mg/kg; i.p), as a positive control were given once daily for 2 weeks. Finally, animals were euthanized and liver samples were obtained for histopathological examination and biochemical measurements including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) levels. Results There is a significant increase in MDA (p < 0.001) level and a significant decrease (p < 0.001) in SOD and GPx contents in diabetic animals. Tropisetron attenuated MDA levels (p < 0.001) and enhanced SOD (p < 0.05) and GPx (p < 0.01) activities accompanied by histopathological improvement in the diabetes liver. Similar results were achieved in the rats treated with the standard drug, namely: glibenclamide. Conclusions Our findings indicate that tropisetron mitigates liver damage in the diabetes rats in part by attenuation of oxidative stress.

Protective Effect of Trans-chalcone Against High-Fat Diet-Induced Pulmonary Inflammation Is Associated with Changes in miR-146a And pro-Inflammatory Cytokines Expression in Male Rats.

High-fat diet (HFD) increases the risk of non-communicable inflammatory diseases including pulmonary disorders. Trans-chalcone is a chalcone with antioxidant and anti-inflammatory effects. This study aimed to explore the effect of this natural compound and molecular mechanism of its effect on HFD-induced pulmonary inflammation. Twenty-eight male Wistar rats were randomly divided into four main groups (n = 7 per each group): control, receiving 10% tween 80; Chal, receiving trans-chalcone, HFD, receiving a high-fat emulsion and 10% tween 80; HFD + Chal, receiving a high-fat emulsion and trans-chalcone. After 6 weeks, the lungs were dissected, and the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and miR-146a were determined using real-time PCR. Moreover, histological analysis was done by hematoxylin and eosin staining. Significant elevations in TNF-α, IL-1ß, IL-6, and miR-146a expression levels (P < 0.001) were observed within the lungs of HFD-fed rats compared with the control. However, oral administration of trans-chalcone reduced TNF-α, IL-1ß, IL-6 (P < 0.001), and miR-146a (P < 0.05) expression levels and also improved HFD-induced histological abnormalities. These findings indicate that trans-chalcone ameliorates lung inflammatory response and structural alterations. It seems that this beneficial effect is associated with the down-regulation of pro-inflammatory cytokines and miR-146a.

The Effects of Natural Clinoptilolite and Nano-Sized Clinoptilolite Supplementation on Lipid Profile, Food Intakes and Body Weight in Rats with Streptozotocin-Induced Diabetes.

Purpose: To determine the effect of natural clinoptilolite (CLN) and nano-sized clinoptilolite (NCLN) on lipid profile, food intakes (FI) and weight changes in streptozotocin (STZ) induced diabetic rats. Methods: In this experimental study, 36 rats were randomly divided into two groups: diabetic group which was injected STZ (60 mg/kg BW), and a non-diabetic group. Three days after diabetes induction, each of these groups was randomly divided into 3 subgroups of 6 animals ((1) control, (2) 1%/food CLN, (3) 1%/food NCLN). The animals were supplemented for 28 days, starting three days after STZ administration. At the end of the study, blood was drawn for biochemical assays. The weights and FIs of the rats were measured at the beginning and end of each week. Results: Our findings revealed that there was no significant change in lipid profile, 28 days after administration of STZ in diabetic rats. Low density lipoprotein (LDL) was increased slightly in diabetic rats treated with NCLN without any significant changes in other lipid profile parameters in the other groups. Weight was reduced significantly in diabetic rats. Administration of CLN and NCLN prevented further weight loss in diabetic rats. All groups treated with STZ had higher food intake during the study. Conclusion: Lack of beneficial changes in lipid profile may be attributed to short study duration, insufficient for appearance of lipid abnormalities. Given the partial improvement in weight status and lack of undesirable effects of clinoptilolite supplementation, further research is recommended in subjects with typ1 diabetes mellitus.

Swimming Exercise Induced Reversed Expression of miR-96 and Its Target Gene NaV1.3 in Diabetic Peripheral Neuropathy in Rats.

Diabetes is a common metabolic disease which leads to diabetic peripheral neuropathy. Recently, the role of microRNA-96 (miR-96) in alleviating neuropathic pain by inhibiting the expression of NaV1.3, an isoform of voltage-gated sodium channels, has been shown. Peripheral nerve injuries result in NaV1.3 elevation. Exercise has beneficial role in diabetes management and peripheral neuropathy. However, the effects of exercise on miR-96 and its target gene NaV1.3 in diabetic rats are unknown. Therefore, the present study investigated the effects of exercise training on the expression of miR-96 and NaV1.3 in diabetic rats. For this purpose, rats were randomly divided into four groups: control, exercise, diabetic and diabetic-exercise groups. Type 2 diabetes was induced by a high-fat diet and the administration of streptozotocin (STZ) (35 mg/kg, i.p.). The exercise groups were subjected to swimming exercise 5 days/week for 10 weeks. At the end of the treatment period, thermal pain threshold, determined through the tail-flick test, and the expression levels of miR-96 and its target gene NaV1.3 were determined by reverse transcription (RT)-PCR in the sciatic nerve tissues of the rats. Data of the present study indicated that diabetes diminished miR-96 expression levels, but significantly upregulated NaV1.3 expression in the sciatic nerve. On exercise training, miR-96 expression was reversed with concurrent down-regulation of the NaV1.3 expression. This study introduced a new and potential miRNA-dependent mechanism for exerciseinduced protective effects against diabetic thermal hyperalgesia.

Effects of IMOD™ on angiogenesis, miR-503 and CDC25 expression levels in heart tissue of diabetic male rats.

OBJECTIVE: Diabetes is associated with vascular complications and impaired angiogenesis. Since angiogenesis plays a crucial role in vascular homeostasis in ischemic heart diseases, in this study, the effect of IMOD™ on miR-503 and CDC25 expression level which are altered in impaired angiogenesis were investigated in heart tissue of diabetic rats. MATERIALS AND METHODS: Forty male Wistar rats (200-250 g) were randomly classified into 4 groups: control (C), IMOD™ (I), diabetes (D), and diabetes+IMOD™ (D+I). For induction of experimental diabetes in animals, a single dose of streptozotocin (STZ; 60mg/kg) was injected intraperitoneally. After 8 weeks of treatment with IMOD™ (20 mg/kg/day), heart tissue samples were removed and used for measurement of miR-503 and CDC25 expression level as well as histological studies. RESULTS: Results of this study showed that diabetes decreased heart tissue angiogenesis which was associated with increased miR-503 and reduced CDC25 expression levels (p<0.05) and IMOD™ could reduce the expression of miR-503 and increase the expression of CDC25 (p<0.05). Moreover, IMOD™ extensively induced angiogenesis in the heart tissue of diabetic group. However, IMOD™ had no significant effect on expressions of miR-503 and CDC25, or angiogenesis in healthy rats. CONCLUSION: This study showed that IMOD™ is able to increase angiogenesis in the heart tissue of diabetic rats. The angiogenic effect of IMOD™ is associated with reduction of miR-503 expression and increased expression of CDC25.

Influence of Two Various Durations of Resistance Exercise on Oxidative Stress in the Male Rat's Hearts.

INTRODUCTION: The previous studies have suggested that alteration in oxidative stress and antioxidant defense depends on various factors, such as mode, intensity, frequency and duration of exercise. In this study, we compared the effects of two various durations of resistance exercise (1 month and 4 month) on oxidative stress and antioxidant status in cardiac tissue. METHODS: Thirty Wistar male rats divided into 3 groups: control (sedentary), exercise-1 (regular exercise for 1 month) and exercise-2 group (regular exercise for 4 months). After the final to the experiment, the rats were anesthetized, and then blood and heart samples were obtained and used to determine glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA) and biochemical estimation. RESULTS: MDA levels between control and exercise-2 groups showed no significant difference, hence, MDA level in exercise-1 group was higher compared to control group (P < .01). The heart GPX activity increased significantly in exercise-2 group regarding other groups (P < .01). The SOD activities of groups were similar. Creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations increased in the exercise-1 compared to the other groups (P < .01). CONCLUSION: Our results indicate that in heart, the adaptation and alteration in oxidative stress and cell injury level depend on duration of exercise.

Swim Training Improves HOMA-IR in Type 2 Diabetes Induced by High Fat Diet and Low Dose of Streptozotocin in Male Rats.

PURPOSE: Insulin resistance plays a key role in the onset and development of type 2 diabetes mellitus (T2DM) and its complications. In this study, we evaluated the effect of swim training on insulin resistance in diabetic rats. METHODS: Forty male Wistar rats were randomly divided into four groups (n=10): sedentary control (Con), sedentary diabetic (Dia), swim trained control (Exe) and swim trained diabetic (Dia+Exe) rats. Diabetes was induced by high fat diet (HFD) and a low dose of streptozotocin (35 mg/kg, i.p). In trained groups, one week after the induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, fasting blood sugar (FBS), oral glucose tolerance test (OGTT), fasting/basal insulin, glycosylated hemoglobin (HbA1c) levels, insulin resistance index, homeostasis model assessment method (HOMA-IR), triglycerides (TG,) total cholesterol (TCh), and high density lipoprotein (HDL) levels in blood were measured. RESULTS: Swimming significantly improved OGTT (P<0.01) and HOMA-IR (P<0.01). Swim training also significantly decreased FBS (p<0.01), fasting/basal insulin (P<0.01), HbA1C (p<0.01), TG (P<0.05), and TCh (P<0.05) levels. It also significantly increased HDL (p<0.05) level. CONCLUSION: Our findings indicate that swim training improved glycemic control and insulin sensitivity in type 2 diabetes caused by high fat diet in male rats.