Vitamin D Protects Against Cardiac Hypertrophy Through the Regulation of Mitochondrial Function in Aging Rats.

Cardiac aging is defined as mitochondrial dysfunction of the heart. Vitamin D (VitD) is an effective agent in ameliorating cardiovascular disorders. In this study, we indicated the protective effects of VitD against cardiac aging. Male Wistar rats were randomly divided into four groups: control (CONT), D-galactose (D-GAL): aged rats induced by D-GAL, D-GAL + Ethanol: aged rats treated with ethanol, and D-GAL + VitD aged rats treated with VitD. Aging was induced by D-GAL at 150 mg/kg via intraperitoneal injection for 8 weeks. Aged rats were treated with VitD (D-GAL + VitD) by gavage for 8 weeks. The serum samples were used to evaluate biochemical factors, and heart tissues were assessed to determine oxidative stress and gene expression. The D-GAL rats exhibited cardiac hypertrophy, which was associated with decreased antioxidant enzyme activity, enhanced oxidative marker, and changes in the expression of mitochondrial genes in comparison with the control rats. Co-treatment with VitD ameliorated all these changes. In conclusion, VitD could protect the heart against D-GAL-induced aging via enhancing antioxidant effects, and the expression of mitochondrial genes.

Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy.

BACKGROUND: Cardiac apoptosis plays a key role in increased morbidity associated with aging-induced-cardiac disorder. Mitochondria play an important role in cardiac apoptosis, and dynamin-related protein 1 (Drp1), as a main mediator of mitochondrial fission, can trigger the mitophagy process to sustain the mitochondrial quality. The present study was done to determine the effect of vitamin D (VitD) treatment on cardiac hypertrophy through mitophagy regulation in aged animals induced by D-galactose (D-GAL). METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups: control, D-GAL (aging group), D-GAL co-injected with VitD (D-GAL ± VitD), and D-GAL plus ethanol (D-GAL ± Ethanol). Aging was induced by an intraperitoneal (i.p.) administration of D-GAL at 150 mg/kg daily for eight weeks and also VitD (400 IU/kg) or ethanol was injected (i.p.) into aging rats. Then, the levels of cardiac mitophagy and cardiac apoptosis were determined by measuring the expression of tensin homologue (PTEN)-induced putative kinase 1 (PINK1), Drp1, Bcl2-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes. Aging in rats was associated with a reduction in mitophagy and also an increase in apoptosis of the heart through down-regulation of Drp1, PINK1, and Bcl2 genes and also up-regulation of Bax. However, VitD improved cardiac hypertrophy through cardiac mitophagy in D-GAL-induced aging rats. CONCLUSION: VitD can inhibit cardiac hypertrophy by an increase in mitophagy and a decrease in apoptosis in the aging heart. The illustration of the suggested mechanism underlying of Vitamin D in cardiac hypertrophy induced by aging.

Swimming exercise improves SIRT1, NF-κB, and IL-1ß protein levels and pancreatic tissue injury in ovariectomized diabetic rats.

OBJECTIVES: In this study, we investigated the beneficial effects of swimming exercise on the SIRT1, NF-κB, IL-1ß protein levels, and pancreatic tissue damage in an ovariectomized diabetic rat model based on the anti-inflammatory effect of exercise. METHODS: Forty mature female Wistar rats were purchased and divided into sham (n=10) and OVX (bilateral ovariectomy) (n=30) groups. The ovariectomized rats were divided into 1-OVX, 2-ovariectomized diabetic (OVX.D), 3-OVX.D + exercise (OVX.D. E). After surgical recovery, animals in the diabetic group received a high-fat diet for one month. Swimming exercise (1 h/day) was performed concurrently with the start of the HFD diet for eight weeks. At the end of the high-fat diet, streptozotocin (30 mg/kg) was injected intraperitoneally. At the end of the second month, pancreatic tissue was collected from the animals after deep anesthesia for molecular evaluation and histology by Western blotting and hematoxylin-eosin, respectively. RESULTS: Swimming exercise significantly decreased inflammatory cytokines and tissue damage, and this decrease in cytokine expression appears to be associated with SIRT1 expression. The increase in SIRT1 by training was associated with decreased NF-κB-p65 and IL-1ß expression and preventing tissue damage. Induction of diabetes in the ovariectomized group (OVX.D) resulted in a significant increase in NF-κB-p65 and IL-1ß proteins and a decrease in the expression of SIRT1 compared with the sham group. However, swimming training significantly reversed these effects compared with the OVX.D group. CONCLUSIONS: Increased inflammation of ß-cells impairs insulin secretion in estrogen insufficiency. Swimming exercise eliminates inflammation in post-menopausal diabetes and supports the potential to prevent pancreatic activity after menopause.

The Restoring Effect of Human Umbilical Cord-Derived Mesenchymal Cell-Conditioned Medium (hMSC-CM) against Carbon Tetrachloride-Induced Pulmonary Fibrosis in Male Wistar Rats.

Objective: Pulmonary toxicity induced by CCl4, a model of idiopathic pulmonary fibrosis (IPF), leads to tissue remodeling and inflammation. Human umbilical cord mesenchymal cell-conditioned medium (hMSC-CM) is a potent anti-inflammatory, antioxidative, and antifibrotic agent. Methods: Forty male Wistar rats were assigned to the control (C), olive oil control (C.O) (hMSC-CM), control (C.Ms), fibrosis (fb), and fibrosis with hMSC-CM (f.Ms) treatment groups. The groups C, C.O, and C.Ms received PBS (200 µl), olive oil (1 ml/kg), and hMSC-CM (100 µg protein/kg), respectively. The fibrosis group was administered with only CCl4 (1 ml/kg). The last group, f.Ms was treated with CCl4 (1 ml/kg) and 100 µg protein/kg IV hMSC-CM. While the treatment with olive oil and CCl4 was performed for 2 days/week from the first week for 12 weeks, the treatment with PBS and hMSC-CM was carried out 2 days/week from week 4th to week 12th. The effect of the UC-MSC culture medium treatment on the lung was evaluated by assessing lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1) genes, and proteins expression by real-time RCR and western blotting, respectively. Results: Lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), transforming growth factor-b1 (TGF-ß1), malondialdehyde (MDA), and oxidative stress levels were markedly higher in the fibrosis group than in the control groups (p ≤ 0.001). Additionally, glutathione (GSH) in the fibrosis group was markedly lower than those in the control groups (p ≤ 0.001). Fibrosis in the UC-MSC treatment group had milder histopathological injuries than in the fibrosis group. Conclusion: hMSC-MSC as a strong anti-inflammatory, antioxidative, and antifibrotic decreases the level of oxidative stress, proinflammatory cytokines, and MDA causing a restoring effect against CCl4-induced pulmonary fibrosis.

Diabetic neovascularization defects in the retina are improved by genistein supplementation in the ovariectomized rat.

Genistein seems to have a protective and therapeutic effect on conditions associated with neovascular growth in the retina. This study investigated the angiogenesis, antioxidant, and anti-inflammatory effect of genistein on the retinas in ovariectomized diabetic rats. In this study, 40 female albino Wistar rats were divided into four groups (n = 8 per group): sham, ovariectomized group (OVX), OVX + diabetes (OVX.D), and OVX.D + genistein (OVX.D.G). OVX induced by removal of bilateral ovaries and then high-fat diet (HFD) and a low dose of streptozotocin (STZ) (1 mg/kg; intraperitoneal (IP) injection) was used for diabetes induction (OVX.D) with 8 weeks of genistein treatment (OVX.D.G). At the end of 8 weeks, the retina was removed under anesthesia. The samples were used to measure extracellular signal-regulated kinase (ERK), matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF), and nuclear factor NF-kappa-B (NF-κB) by western blotting and inflammatory factors ELISA and oxidative stress. Measurements of glutathione (GSH) and malondialdehyde (MDA) showed that OVX and especially OVX.D significantly decreased GSH and increased MDA level in the retina, but genistein reversed these effects in OVX.D.G groups. Also, OVX and OVX.D significantly increased VEGF, MMP-2, p-ERK, NF-κB, interleukin-1beta (IL-1ß), and tumor necrosis factor alpha (TNFα) expression in the retina of OVX and OVX.D groups in comparison to the sham group (p < 0.05). However, a significant reduction of these proteins was observed in the genistein-treated group (p < 0.05). In conclusion, bilateral ovariectomy and subsequently estrogen deficiency caused the development of inflammation, neovascularization, and then retinopathy in STZ-induced diabetic ovariectomized rats. On the basis of the results, genistein administration may be a practical approach for improving symptoms and complications of ovariectomized diabetic retinopathy.

Synergism effect of swimming exercise and genistein on the inflammation, oxidative stress, and VEGF expression in the retina of diabetic-ovariectomized rats.

AIMS: Retinal neovascularization is one of the visual disorders during the postmenopausal period or types two diabetes. Physical activities and also phytoestrogens with powerful antioxidant features have been widely considered to improve nervous system diseases. Therefore, this study investigated the effects of genistein, swimming exercise, and their co-treatment on retina angiogenesis, oxidative stress, and inflammation in diabetic-ovariectomized rats. MAIN METHODS: Wistar rats were randomly divided into six groups (n = 8 per group): sham, ovariectomized group (OVX), OVX + diabetes (OVX.D), OVX.D+ genistein (1 mg/kg, eight weeks; daily SC), OVX.D + exercise (eight weeks), and OVX.D+ genistein+exercise (eight weeks). At the end of 8 weeks, the retina was removed under anesthesia. The assessed effects of treatment were by measuring MiR-146a and miR-132 expression via RT-PCR, the protein levels of ERK, MMP-2, VEGF, and NF-κB via western blotting, inflammation, and oxidative stress markers levels via the Eliza. KEY FINDINGS: The results showed miR-132, miR-146b, and MMP-2, NF-κB, ERK, VEGF, TNF-α, IL-1ß proteins, and MDA factor in the OVX.D group were increased, but glutathione (GSH) was decreased in comparison with the sham and OVX groups. Both exercise and genistein treatment has reversed the disorder caused by diabetes. However, the combination of exercise and genistein was more effective than each treatment alone. SIGNIFICANCE: It can be concluded that the interaction of exercise and genistein on microRNAs and their target protein was affected in the inflammation, stress oxidative, and extracellular matrix metalloproteinase pathways, can leading to a decrease in impairment of retinal neovascularization of the ovariectomized diabetic rats.

Renoprotective effects of tropisetron through regulation of the TGF-ß1, p53 and matrix metalloproteinases in streptozotocin-induced diabetic rats.

Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Masson's trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-ß1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-ß1, p53, and expression of extracellular matrix metalloproteinases.

A Review on the Serum Electrolytes and Trace Elements Role in the Pathophysiology of COVID-19.

All the world is involved in the COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus is a positive-sense RNA and has an envelope. There is no specific drug for this disease and treatment methods are limited. Malnutrition and electrolyte imbalance can make dysfunction in the immune system and impairment of the immune system causes increasing the risk of infection. Understanding the aspects of biological features of the virus will help the development of diagnostic tests, pharmacological therapies, and vaccines. Here, we review and discuss increasing and decreasing some trace elements and imbalance of serum and plasma electrolytes involving in COVID-19.

Exercise training attenuates diabetes-induced cardiac injury through increasing miR-133a and improving pro-apoptosis/anti-apoptosis balance in ovariectomized rats.

OBJECTIVES: The useful and effective role of exercise program to prevent cardiac tissue apoptosis and fibrosis in ovariectomized type 2 diabetic (T2DM) rats (OVR.D) is well known. The current study aimed to investigate the simultaneous effects of T2DM and swimming plan on the expression of some apoptotic, anti-apoptotic biomarkers and glycogen changes in the cardiac muscle tissue of ovariectomized (OVR) rats. MATERIALS AND METHODS: Forty rats were randomly sorted into 4 equal categories; sham, OVR, OVR.D and diabetic ovariectomized with an 8 week of swimming plan (OVR.D.E). Lipid profile and miR-133, Bcl-2, Bax, caspase-3 and caspase-8 levels were evaluated in the cardiac tissue. RESULTS: Ovariectomy significantly (P-value<0.05) increased cholesterol, triglyceride, LDL, Bax, caspase-3, caspase-8 and decreased (P-value<0.05) HDL, miR-133, Bcl-2 in the cardiac tissue and a further reduction in the expression of miR-133, Bcl-2 and an enhancement in Bax, caspase-3 and caspase-8 in OVR.D rats was observed (P-value<0.01). However, exercise training significantly reversed all the measured parameters (P-value<0.05). Also, exercise training improved abnormal tissue structure, fragmentation and irregular form of glycogen granules in the OVR.D.E compared to OVR and OVR.D animals. CONCLUSION: Exercise training could prevent the cardiac disturbance, enhance the expression of anti-apoptotic markers and decrease apoptotic biomarkers in the hearts of OVR.D animals. Therefore, based on the findings of this study suggested using the exercise's beneficial effects for prevention of the cardiac cell death in OVR.D animals.

Fibrotic and apoptotic markers alteration in ovariectomised rats: addition of swimming training preserves lung architecture.

CONTEXT: The important role of exercise in pulmonary function during menopause is not well known. Oestrogen deficiency in ageing female mice is accompanied by increase in apoptotic markers such as caspase3 in the lung. OBJECTIVE: The present study was designed to investigate whether swimming training will ameliorate fibrosis and apoptosis resolution in the ovariectomy-induced lung injury rats. MATERIAL AND METHOD: Thirty female rats were assigned to three groups (n = 10 in each group): sham; rats underwent bilateral laparotomy without ovariectomy, OVX; rats underwent bilateral ovariectomy, OVX.Exe; ovariectomised rats that underwent swimming training for eight weeks. At the end of eight weeks, the lungs were harvested and protein expressions in whole lung tissues were analysed by western blotting technique. RESULT: Analysis of proteins expression in the lung showed significant differences between exercise and ovariectomised group (p < .05). CONCLUSION: The present study indicates strong potential of exercise in experimental oestrogen deficiency-induced lung damage.

Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung.

OBJECTIVES: The role of isoflavones in pulmonary structure and function during menopause is not well studied. Moreover, the important role of estrogen in the physiological function of respiratory system has been revealed. Genistein, as an isoflavone, mimics estrogenic in diabetic and ovariectomized rats. Here, we hypothesized that genistein would reverse changes in the protein expression levels related to estrogen deficiency in the lung of ovariectomized diabetic rats. MATERIALS AND METHODS: Wistar female rats were assigned to four experimental groups (n=10 in each group): sham, rats underwent laparotomy without removing the ovaries; OVX, rats that underwent ovariectomy; OVX.D, rats underwent bilateral ovariectomy and were fed a high-fat diet (HFD); OVX.D.G, ovariectomized diabetic rats with genistein administration (1 mg/kg /day). After ovariectomy, rats continued to feed HFD for a 4-week period. After 4 weeks of HFD feeding, a single dose of 30 mg/kg of streptozotocin was administered in the diabetic group. Genistein was administered for eight weeks. At the end of the experiment, lung tissue was removed and Western blotting technique and hematoxylin-eosin staining were used for evaluation of the lung. RESULTS: Treatment with genistein significantly decreased inflammatory and apoptotic biomarkers in the ovariectomized diabetic rats compared to non-treated animals (P<0.05). Also, genistein exerted a protective effect in the lung architecture. CONCLUSION: Genistein partly reversed ovariectomy-induced changes in apoptotic and inflammatory biomarkers in the lung. Our data suggest that genistein treatment as a natural replacement therapy may prevent the estrogen deficiency effects in the lung of diabetic menopausal women.

Effects of genistein and swimming exercise on spatial memory and expression of microRNA 132, BDNF, and IGF-1 genes in the hippocampus of ovariectomized rats.

OBJECTIVES: The aim of the present study was to investigate the effects of genistein and exercise on the spatial memory and expression of microRNA-132, BDNF, and IGF-1 in the hippocampus of ovariectomized rats. MATERIALS AND METHODS: Sixty animals were divided into six groups of control, sham, ovariectomy (OVX), ovariectomized with 8 weeks of genistein administration (OVX.G), with 8 weeks of swimming training (OVX.E), and with 8 weeks of both of them (OVX.G.E). The effect of genistein and/or exercise was evaluated by measuring microRNA-132, BDNF, and IGF-1 expression levels in the hippocampus tissue. Grafts were analyzed using Real-time polymerase chain reaction for microRNA-132, BDNF, IGF-1, and spatial memory via a Morris water maze (MWM). RESULTS: Our findings showed that ovariectomy decreased the expression of microRNA-132, BDNF, and IGF-1 in the hippocampus (P<0.05) in comparison with the sham group as well as performance in the water maze (P<0.05). Also according to results ovariectomized groups that were treated with genistein/exercise or both of them showed significant difference in expression of microRNA-132, BDNF, and IGF-1 in the hippocampus (P<0.05) and decreased latency in MWM (P<0.05) compared with the OVX group but combination treatment was more effective in the OVX.G.E group in comparison with OVX.E and OVX.G groups. CONCLUSION: Overall our results emphasized that combination treatment with genistein and exercise could improve microRNA-132, BDNF, and IGF-1 expression in the hippocampus as well as the spatial memory of ovariectomized rats. These effects may have beneficial impacts on the menopausal period.

Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis.

OBJECTIVES: Genistein, as a phytoestrogen found in legumes, has several biological activities in general and anti-diabetic activity particularly. In this study, we investigated the effect of genistein on proteins involved in ß-cell proliferation, survival and apoptosis to further reveal its anti-diabetic potential in the ovariectomized diabetic rat. MATERIALS AND METHODS: We used three-month-old female Wistar rats that either underwent ovariectomy (OVX) or received a sham surgery (Sham). In a subsequent series of experiments, OVX rats received high-fat diet and low dose STZ to induce diabetes (OVX.D) and genistein treatment (OVX.D.G). Western blot analysis was used for the assessment of phosphorylation of ERK1/2 and AKT and expression of Bcl-2 and caspase-3 in pancreas tissue. Hematoxylin-Eosin (H&E) staining was used for histopathological assessment. RESULTS: Genistein induced AKT and ERK1/2 phosphorylation protein expression of Bcl-2 in the pancreas. In addition, genistein suppressed protein level of caspase-3. Administration of genistein significantly improved hyperglycemia in ovariectomized diabetic rat, concomitant with improved islet ß-cell morphology and mass. CONCLUSION: These findings suggest that the beneficial antidiabetic effect of genistein partially mediated by directly modulating pancreatic ß-cell function via activation of the AKT, ERK1/2, and Bcl-2, as cell survival and anti-apoptotic factors, and decreasing of proapoptotic caspase-3.

Effect of genistein on expression of pancreatic SIRT1, inflammatory cytokines and histological changes in ovariectomized diabetic rat.

OBJECTIVES: Genistein is reported to have anti-diabetic and anti-inflammatory functions, in particular, direct effects on ß-cell proliferation and insulin secretion. In this study, we investigated the anti-inflammatory effect of genistein on the pancreatic ß-cells in ovariectomized diabetic rat. MATERIALS AND METHODS: Forty female rats were divided into four groups: sham, bilateral ovariectomy (OVX), OVX.D (OVX+diabetes) and OVX.D.G (OVX.D+genistein). After bilateral ovariectomy, rats in the diabetic groups were fed high-fat diet (HFD), ad libitum for 4 weeks, and then a low dose of streptozotocin (STZ) (30 mg/kg) injected intraperitoneally. Genistein (1 mg/kg/day; SC) was administrated for 8 weeks. At the end of 8 weeks, pancreas tissue was removed and used for western blotting and Hematoxylin-Eosin staining. RESULTS: Treatment with genistein declined inflammation and tissue injury, and this decline was correlated with the expression of SIRT1. OVX and OVX.D significantly increased Nf-κB and IL-1ß expression and decreased SIRT1 levels compared to sham group (P<0.05). Significant reduction of Nf-κB and IL-1ß, and increasing of SIRT1 were observed during genistein treatment (P<0.05). CONCLUSION: Estrogen deficiency alone or with HFD increased pancreatic inflammation. However, subcutaneous administration of gtenistein prevented from these inflammatory changes in the pancreas of a surgery animal model of ovariectomy with or without diabetes. Our results support the potential preventing effect of genistein from pancreatic injury.

Apoptosis and Histopathology of the Heart after Renal Ischemia-Reperfusion in Male Rat Running title: Ischemia-Reperfusion Injury

ABSTRACT Ischemia-reperfusion injury was seen in strokes, myocardial infarctions, acute kidney injury, mesenteric ischemia, liver and systemic shock. Renal ischemia-reperfusion is more importance in the setting of kidney transplantation that affects distant organs. In this study forty Male Albino Wistar rats (200-250g) were randomly divided in four group (n=10) including control, sham operation group, nephrectomy and IRI group. All rats anesthetized with intraperitoneal injection of ketamine (50 mg/kg) and xylazine (10 mg/kg) and maintained the core body temperature at approximately 37°C. For inducing IRI group, it was performed right nephrectomy, and in continuing, the left kidney pedicle occluded to 45 min via nontraumatic microvascular clamp for making ischemia that followed 24 hours reperfusion. TUNEL assay was used to detect the cardiac apoptotic cells. Hematoxylin-Eosin staining and periodic acid-Schiff (PAS) procedure was used to histopathological assessment and glycogen accumulation respectively. There was more heart damage at 24 h reperfusion in IRI group. Renal IRI group showed myocardial degeneration, necrosis and increasing connective tissue in myofibril. There were apparent hypertrophy and swelling of myofibril, fragmentation and vacuolization of sarcoplasm. In addition, it was shown elevated apoptotic cell at 24 hours reperfusion in renal IRI group than sham group. There were increases of glycogen accumulation in cardimyocyte of renal IRI group. Our findings suggest that renal IRI-induced cardiac damage, accompanied by an accumulation of glycogen granules, induced apoptosis and histological changes in cardiomyocytes.

Involvement of microRNA-133 and -29 in cardiac disturbances in diabetic ovariectomized rats.

OBJECTIVES: Menopause and diabetes obviously increase the risk of cardiovascular disease in women. The aims of the present study were to evaluate the effects of ovariectomy in type 2 diabetes on the histology and expression of miRNA-29, miRNA-133, IGF-1 and Bcl-2 genes and Bcl-2 protein and caspase 3 activity in the hearts of female rats. MATERIALS AND METHODS: Forty Female Wistar rats were divided into four groups: control, sham, ovariectomized (OVX), and ovariectomized with type 2 diabetes (OVX.D). After the 8-week experiment, the histological evaluation of the heart tissue was performed using H&E staining and PAS analysis, and cardiac expression of miRNA-29, miRNA-133, IGF-1, and Bcl-2 were evaluated using real-time PCR, and Bcl-2 protein and caspase 3 activity were evaluated using Western blot and ELISA. RESULTS: Ovariectomy significantly decreased miRNA-29, miRNA-133, IGF-1, and BCL-2 expression and Bcl-2 protein and increased caspase 3 activity in the heart compared to sham animals group (P<0.05). Type 2 diabetes in ovariectomized rats markedly decreased expression of miRNA-29, miRNA-133, IGF-1, BCL-2 genes, and Bcl-2 protein, and increased caspase 3 activity and reduced collagen and fibroblast tissue and glycogen granule deposition in relation to OVX group (P<0.05). CONCLUSION: Our findings suggest that type 2 diabetes and menopause synergically could enhance the cardiac fibrosis through dysregulation of miRNA-29, miRNA-133, IGF-1, and Bcl-2 genes expression and Bcl-2 protein and upregulation of caspase 3 activity.

Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats.

OBJECTIVES: The beneficial and more potent role of exercise to prevent heart apoptosis in ovariectomized rats has been known. The aim of this study was to examine the effects of swimming training on cardiac expression of Bcl-2, and Mir-133 levels and glycogen changes in the myocyte. MATERIALS AND METHODS: Forty animals were separated into four groups as control, sham, ovariectomy (OVX) and ovariectomized group with 8 weeks swimming training (OVX.E). Training effects were evaluated by measuring lipid profiles, Bcl-2 and Mir-133 expression levels in the cardiac tissue. Grafts were analyzed by reverse transcription-polymerase chain reaction for Bcl-2 mRNA and Mir-133 and by Western blot for Bcl-2 protein. RESULTS: Ovariectomy down-regulated Bcl-2 and Mir-133 expression levels in the cardiac tissue, and swimming training up-regulated their expression significantly (P<0.05). CONCLUSION: Our results showed that regular exercise as a physical replacement therapy could prevent and improve the effects of estrogen deficiency in the cardia.

Effect of renal ischemia-reperfusion on lung injury and inflammatory responses in male rat.

OBJECTIVES: Acute kidney injury (AKI), a syndrome characterized by decreased glomerular filtration, occurs in every 1 of 5 hospitalized patients. Renal ischemia-reperfusion, one of the main causes of AKI, is of particular importance in the setting of kidney transplantation. MATERIALS AND METHODS: Sixty male rats were divided into four groups including control, nephrectomy, sham surgery and renal ischemia-reperfusion (IRI) group. The rats were anesthetized with intraperitonealketamin and xylazin. For making IRI group, right nephrectomywas performed, and after a week, the left kidney pedicle was occluded for 45 min for making ischemia that followed by 24 hr reperfusion. At the end of reperfusion phase, the lung tissues were isolated to be used in immunohistochemical and histological assays. Immunohistochemical assay was used to evaluate Bcl-2 and TNF-α, and hematoxylin-eosin staining assay was used to histopathology. RESULTS: lung tissues injury after renal ischemia-reperfusion was revealed by immunohistochemistry analysis to increase TNF-α level and decrease Bcl-2 (an anti-apoptotic protein) level. Lung injury and necrosis was discovered by hematoxylin-eosin staining to be more evident in IRI group than sham and control groups. CONCLUSION: The results demonstrated that increase in TNF-α and decrease in Bcl-2 levels in lungs induces the pulmonary inflammatory damage in renal IRI model.

Influence of Aloe Vera gel on dermal wound healing process in rat.

In this topical study the influence of Aloe Vera, on the wound healing process was investigated in 63 male rats with microscopic and cell count methods. On the day of surgery a round wound, of diameter 20 mm, was created on the back of rats necks under sterile conditions. The surgery day was determined as day zero (0). Then the rats were divided randomly into control and experimental groups 1 and 2. Animals in each group were sub-divided to three smaller groups, investigated every 4, 7, and 14 days. From day 0, wound surfaces were covered with gel once daily in experimental group 1 and twice daily, for 12 h interval, in experimental group 2. Each rat received 30 g of the gel. The wound surface and healing were assessed on days 4, 7, and 14, and then a sample from the wound was prepared and investigated microscopically. The results show that the number of neutrophil, macrophage, and fibroblast cells and the wound thickness in the control group were statistically different from the experimental groups. It was found that the wound diameter thickness in the experimental group was greatly lower due to twice administration of gel and the power of wound healing was more than other groups.

The Teratogenic Effects of Flurazepam Intake during Organogenesis of the Rat Fetus.

ABSTRACT Flurazepam is a long acting drug with sedative, hypnotic, anxiolytic, relaxant, and anti-epileptic properties. The drug is a benzodiazepine and is commonly used by adults, including pregnant women, intentionally or sometimes unintentionally during their pregnancy. It is increasingly used these days, and therefore, it seems a special problem to the clinician treating anxiety disorders in women. It should be noticed that flurazepam exposure during pregnancy may have teratogenic effects on the fetus. Until now, many studies have been conducted on drug side-effects in poisonings, behavioral disorder, and anxiety reactions, but there is no accurate report about the teratogenic effect of flurazepam. In this study, teratogenicity flurazepam intake during pregnancy and its effects on fetus development was investigated. About 30 virgin rats of known age and weight were used. After being pregnant, they were divided into three groups: Negative and positive control group, case groups exposed for 1 to 6 mg/kg/day. The fetuses were first studied macroscopically regarding anomalies, and then histological and histochemically to inspect the defects of tissue organogenesis. Our results show that there was significant difference in the weight and length of the cases compared to the control group. The statistical results indicate that flurazepam intake during the second half of pregnancy can lead to irreversible anomalies. It seems that benzodiazepine therapy among pregnant woman would be better to avoid during the first trimester and multidrug regimens.