Protective effects of BiP inducer X (BIX) against diabetic cardiomyopathy in rats.

Diabetic cardiomyopathy (DC) is associated with impaired endoplasmic reticulum (ER) function, development of ER stress, and induction of cardiac cell apoptosis. Preventive effects of BiP inducer X (BIX) were investigated against DC characteristic changes in a type 2 diabetes rat model. To establish diabetes, a high-fat diet and a single dose of streptozotocin were administered. Then, animals were assigned into the following groups: control, BIX, diabetic animals monitored for one, two, and three weeks. Diabetic rats were treated with BIX for one, two, and three weeks. Expressions of various ER stress and apoptotic markers were assessed by immunoblotting method. CHOP gene expression was assessed by Real-time PCR. Tissue expression of BiP was evaluated by immunohistochemistry method. Hematoxylin and eosin and Masson's trichrome staining were performed to assess histological changes in the left ventricle. Cardiac cell apoptosis was examined using TUNEL assay. BIX administration suppressed the activation of the ER stress markers and cleavage of procaspase-3 in the diabetic rats. Likewise, tissue expression of BiP protein was increased, while CHOP mRNA levels were decreased. These results were accompanied by reducing cardiac fibrosis and myocardial cell apoptosis suggesting protective effects of BIX against the development of DC by decreasing cardiomyocyte apoptosis and fibrosis.

Impacts of epidural electrical stimulation on Wnt signaling, FAAH, and BDNF following thoracic spinal cord injury in rat.

Electrical stimulation (ES) has been shown to improve some of impairments after spinal cord injury (SCI), but the underlying mechanisms remain unclear. The Wnt signaling pathways and the endocannabinoid system appear to be modulated in response to SCI. This study aimed to investigate the effect of ES therapy on the activity of canonical/noncanonical Wnt signaling pathways, brain-derived neurotrophic factor (BDNF), and fatty-acid amide hydrolase (FAAH), which regulate endocannabinoids levels. Forty male Wistar rats were randomly divided into four groups: (a) Sham, (b) laminectomy + epidural subthreshold ES, (c) SCI, and (d) SCI + epidural subthreshold ES. A moderate contusion SCI was performed at the thoracic level (T10). Epidural subthreshold ES was delivered to upper the level of T10 segment every day (1 hr/rat) for 2 weeks. Then, animals were killed and immunoblotting was used to assess spinal cord parameters. Results revealed that ES intervention for 14 days could significantly increase wingless-type3 (Wnt3), Wnt7, ß-catenin, Nestin, and cyclin D1 levels, as well as phosphorylation of glycogen synthase kinase 3ß and Jun N-terminal kinase. Additionally, SCI reduced BDNF and FAAH levels, and ES increased BDNF and FAAH levels in the injury site. We propose that ES therapy may improve some of impairments after SCI through Wnt signaling pathways. Outcomes also suggest that BDNF and FAAH are important players in the beneficial impacts of ES therapy. However, the precise mechanism of BDNF, FAAH, and Wnt signaling pathways on SCI requires further investigation.

Rosa canina L. methanolic extract prevents heat stress-induced memory dysfunction in rats.

NEW FINDINGS: What is the central question of this study? Heat stress has harmful effects on the brain structure and synaptic density via induction of oxidative stress and neuroinflammation, which result in neuronal damage in the hippocampus and thereby cognitive impairments. In this study, we investigate the effect of Rosa canina treatment on cognitive function in heat stress-exposed rats and its underlying mechanisms. What is the main finding and its importance? We show that R. canina improves cognitive deficits induced by heat stress by attenuation of oxidative stress and neuroinflammation and by upregulation of synaptic proteins in the hippocampus. ABSTRACT: The aim of the study was to evaluate the effects of aqueous methanolic extract of Rosa canina (RC) dried fruits on oxidative stress, inflammation, synaptic degeneration and memory dysfunction induced by heat stress (HS) in rats. Sixty adult male Wistar rats were randomly divided into five groups as follows: the control group received normal saline (NS); the HS group was exposed to heat stress (43°C) for 15 min once a day for 2 weeks; and HS+R groups were exposed to heat stress and received one of three doses (250, 500 or 1000 mg kg-1 ) of RC methanolic extract for 2 weeks. A passive avoidance test and a Y-maze test were performed to assess learning and memory. The levels of reactive oxygen species were assessed. The serum cortisol concentration and hippocampal total antioxidant capacity, superoxide dismutase and glutathione peroxidase were also detected using spectrophotometry. The protein expressions of c-Fos, heat-shock protein-70, tumour necrosis factor-α, growth-associated protein 43, post-synaptic density-95 and synaptophysin were evaluated in the hippocampal tissue. The results showed that RC significantly improved cognitive dysfunction induced by HS, which was accompanied by downregulation of tumour necrosis factor-α and upregulation of growth-associated protein 43 and synaptophysin proteins in the hippocampus of HS-exposed rats. Furthermore, RC significantly attenuated serum cortisol concentrations and upregulated heat shock protein-70 and c-Fos in the hippocampus. In addition, the administration of RC attenuated reactive oxygen species levels and enhanced antioxidant defense in the hippocampus. These findings indicate that RC attenuated the deleterious effect of HS on cognition through its antioxidant properties and by enhancing synaptic function and plasticity.

Ghrelin attenuated hyperalgesia induced by chronic nitroglycerin: CGRP and TRPV1 as targets for migraine management.

Background According to the neurovascular theory of migraine, activation of the trigeminovascular system contributes to the development of migraine. This study examined the effects of chronic intraperitoneal ghrelin (150 µg/kg) treatment on the development of chronic migraine induced by intermittent injection of nitroglycerin 10 mg/kg. Methods Baseline and post-drug (2 h following nitroglycerin injection) mechanical and thermal sensitivity were assessed by von Frey hair and tail immersion tests, respectively on days 1, 3, 5, 7, 9 and 11. Moreover, we investigated the effect of ghrelin treatment on nitroglycerin-induced aversive behavior by using a two-chamber conditioned place aversion paradigm. At the end of behavioral testing, on day 11, animals were sacrificed and plasma concentration of calcitonin gene-related peptide was measured using a rat-specific enzyme-linked immunosorbent assay kit. Also, real time polymerase chain reaction was used to quantify mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid 1 in the trigeminal ganglion. Results Our results indicated that nitroglycerin activated the trigeminovascular system, which was reflected by mechanical and thermal hypersensitivity and elevation of mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid-1, as migraine markers, and plasma calcitonin gene-related peptide levels. Moreover, chronic nitroglycerin injection induced conditioned place aversion and body weight loss. Nevertheless, ghrelin modulated nitroglycerin-triggered changes in transient receptor potential vanilloid-1 and calcitonin gene-related peptide expression, and mitigated nitroglycerin-induced hyperalgesia. Conclusion These results provide the first convincing evidence that ghrelin has a modulating effect on central sensitization induced by chronic intermittent nitroglycerin, and its antinociceptive effect may be related to a reduction of these factors in the trigeminal ganglion.

Oxidative stress-induced renal telomere shortening as a mechanism of cyclosporine-induced nephrotoxicity.

Due to the association of oxidative stress and telomere shortening, it was aimed in the present study to investigate the possibility whether cyclosporine-A exerts its nephrotoxic side effects via induction of oxidative stress-induced renal telomere shortening and senescent phenotype in renal tissues of rats. Renal oxidative stress markers, 8-hydroxydeoxyguanosine, malondialdehyde, and protein carbonyl groups were measured by standard methods. Telomere length and telomerase activity were also evaluated in kidney tissue samples. Results showed that cyclosporine-A treatment significantly (P < 0.05) enhanced renal malondialdehyde, 8-hydroxydeoxyguanosine, and protein carbonyl groups levels, decreased renal telomere length, and deteriorated renal function compared with the controls. Renal telomerase activity was not affected by cyclosporine-A. Renal telomere length could be considered as an important parameter of both oxidative stress and kidney function. Telomere shortening and accelerated kidney aging may be caused by cyclosporine-induced oxidative stress, indicating the potential mechanism of cyclosporine-induced nephrotoxicity.

Metformin protects PC12 cells against oxygen-glucose deprivation/reperfusion injury.

Oxidative stress has a causative role in ischemic reperfusion-induced cell death. Evidence has shown that metformin is capable to reduce ischemic reperfusion injuries. The current study investigated the effect of metformin on ischemia/reperfusion-induced apoptosis in PC12 cells by evaluation of Bcl-2 family proteins expression. Cells were exposed to a time-dependent in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) injury and then treated with metformin. The intracellular reactive oxygen species (ROS) levels were measured. Western blotting was used to examine the expression of anti- and pro-apoptotic proteins. Moreover, the number of apoptotic cell death was evaluated by TUNEL assay. Our results showed that metformin attenuated ROS generation, downregulated pro-apoptotic BAX expression, and upregulated expression of the Bcl-2 protein in the PC12 cells. Moreover, metformin reduced cell death under OGD/R condition which was confirmed by lower apoptotic cell death in the TUNEL assay. These findings suggest that neuroprotective effect of metformin on OGD/R-induced cell death is possibly mediated by inhibition of ROS-induced apoptosis pathway.

Chronic ghrelin treatment reduced photophobia and anxiety-like behaviors in nitroglycerin- induced migraine: role of pituitary adenylate cyclase-activating polypeptide.

Chronic migraine is a debilitating disorder that has a significant impact on patients and society. Nearly all migraineurs frequently reported light sensitivity during a headache attack. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the activation of trigeminal system and migraine pain. To identify the effect of chronic ghrelin treatment on endogenous PACAP and associated symptoms of migraine, an experimental chronic migraine model was induced by intermittent intraperitoneal (i.p) injection of nitroglycerin (NTG). Photophobia and anxiety-like behaviors were determined in the modified elevated plus maze on days 2, 4, 6, 8, and 10 and in the light/dark box on days 3, 5, 7, 9, and 11. Blood levels of PACAP and cortisol were assessed by enzyme-linked immunosorbent (ELISA) kits. Chronic injection of NTG evoked photophobia and anxiety-like behaviors and treatment with ghrelin (150 µg/kg) for 11 days effectively attenuated photophobia and anxiety-like behaviors in the both paradigms. We further found that NTG increased the blood levels of PACAP and cortisol, which was significantly reduced by ghrelin treatment. Additionally, staining with Hematoxylin and Eosin (H&E) revealed that ghrelin reduced NTG-induced increase in the number of satellite glial cells in the trigeminal ganglion. Furthermore, for the first time we showed that repeated administrations of NTG increased white blood cell (WBC) counts and mean platelet volume (MPV), and decreased platelet counts. These results indicated that ghrelin decreased migraine associated symptoms possibly through attenuating endogenous PACAP and cortisol levels. Therefore, ghrelin may hold therapeutic potentialities in managing the chronic migraine.

Aerobic exercise training improves memory function through modulation of brain-derived neurotrophic factor and synaptic proteins in the hippocampus and prefrontal cortex of type 2 diabetic rats.

Aims/Introduction: Defective insulin signaling in the brain may disrupt hippocampal neuroplasticity resulting in learning and memory impairments. Thus, this study investigated the effect of aerobic exercise training on cognitive function and synaptic protein markers in diabetic rats. Materials and methods: Twenty male Wistar rats (200-250 g), were fed on high-fat diet and received a low dose of streptozotocin (35 mg/kg, i.p) to induce type 2 diabetes. Then diabetic animals were randomly divided into sedentary and training groups. The exercise training program was treadmill running at 27 m/min for 60 min/day for 8 weeks. One day after the last training session, Morris Water Maze (MWM) task was performed to evaluate spatial learning and memory. Then, the hippocamp and prefrontal cortex tissues were instantly dissected for immunoblotting assay of BDNF, GSK-3ß, p-GSK-3ß, P38, p-P38, ERK1/2, p-ERK1/2, heat shock protein-27 (HSP27), SNAP-25, synaptophysin, and PSD-95. Independent t-test analysis and two-way ANOVA was used to determine the differences under significance level of 0.05 using the 26th version of IBM SPSS statistical software. Results: The results showed that aerobic exercise improved memory as assessed in the MWM task. Moreover, aerobic exercise up-regulated HSP27 and BDNF protein levels in the prefrontal cortex, and hippocampus coincided with robust elevations in SNAP25 and PSD-95 levels. Moreover, exercise reduced phosphorylated P38, while increased p-ERK1/2 and p-GSK-3ß (p). Conclusion: Our findings suggest that aerobic exercise may debilitate the harmful effects of diabetes on the cognitive function possibly through enhancing synaptic protein markers.

Swimming training modulates lung injury induced by ovariectomy in diabetic rats: involvement of inflammatory and fibrotic biomarkers.

CONTEXT: Previous studies have noted that the incidence of inflammatory and fibrotic diseases is higher in diabetic menopausal women. OBJECTIVE: In the present study, we evaluated effects of swimming training on inflammatory and fibrotic biomarkers in the lung of ovariectomized diabetic rats. MATERIALS AND METHODS: Forty female rats were assigned into four groups: sham; rats underwent surgery without ovariectomies, OVX: rats that underwent ovariectomies, OVX.Dia: ovariectomized rats with high-fat diet, OVX.Dia. Exe: ovariectomized diabetic rats with 8 weeks of swimming training. At the end of experiment, protein expressions were assessed with western blot. Lung sections were subjected to immunohistochemical and haematoxylin eosin staining. RESULTS: There was a significant difference in the protein expressions between exercise and ovariectomized diabetic groups (p < .05). CONCLUSION: The present study showed strong potential of swimming training on oestrogen deficient diabetic lung. These data encourage further investigation into the inclusive effects of exercise in menopausal diabetic women.

Moderate Aerobic Training Inhibits Middle-Aged Induced Cardiac Calcineurin-NFAT Signaling by Improving TGF-ß, NPR-A, SERCA2, and TRPC6 in Wistar Rats.

OBJECTIVE: The purpose of this study was to investigate the effect of moderate-intensity training on the calcineurin/ nuclear factor of activated t-cells (NFAT) pathway and factors affecting it in the middle-age Wistar rats. MATERIALS AND METHODS: In this experimental study, 40 young (n=10, 4-month-old) and middle-aged (n=30, 13-15 months old) Wistar rats were included in this experimental study. All young and 10 middle-aged rats did not training and served as a control comparision; while the remaining 20 middle-aged rats were trained at moderate intensity for 4-weeks (n=10) or 8-weeks (n=10) on a treadmill (speed: 16 m/minutes, slope: 0%, distance: 830 m, duration: 54 minutes). RESULTS: Calcineurin tissue expression was increased in the middle-aged control rats compared to the young control rats (P=0.001). Expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERC2A), natriuretic peptide receptor-A (NPR-A), phospholamban (PLB), plasma membrane Ca2+ ATPase (PMCA4b), and p-AKT was significantly decreased in the heart tissue of middle-aged control compared to the young control rats (P=0.001). Furthermore, transforming growth factor beta (TGF-ß), including transient receptor potential canonical 6 (TRPC6), were up-regulated in the heart tissue of middle-aged control compared to the young control rats (P=0.001). However, aerobic training inhibited this pathway and reversed all changes in the trained middle-aged rats. CONCLUSION: Aerobic training effectively inhibited the calcineurin/NFATc pathway and modulated intracellular Ca2+ levels at least partially by restoring NPR-A, SERCA2, p-PLB, and p-AKT, and decreasing TRPC6 and TGF-ß levels.

Resistance training attenuates circulating FGF-21 and myostatin and improves insulin resistance in elderly men with and without type 2 diabetes mellitus: A randomised controlled clinical trial.

Fibroblast growth factor 21 (FGF-21) and myostatin have been proposed to be potential therapeutic target for insulin resistance in age-related metabolic disorders including type 2 diabetes (T2D). Moreover, despite the potential metabolic effect of resistance training on insulin resistance, aging, and T2D; the effect of this type of exercise training on FGF-21 and myostatin in elderly men with and without T2D are unknown. Forty-four elderly men were assigned to either the RT training (RT; without T2D: 12, with TD2 = 10) or the control group (C; without T2D: 12, with TD2 = 10). The RT group performed 12-wk resistance training intervention, 3 days/wk, 10 repetitions with 70% 1RM. At the baseline, the elderly men with T2D had a higher FGF-21 (p = 0.002) and myostatin (p = 0.02) concentrations and lower muscle strength (p = 0.01) than the elderly men without T2D. RT resulted in significant decrease in FGF-21 and myostatin concentration and increase in muscle strength in both elderly men with and without T2D (P = 0.001, for all) as well as decrease in HOMA-IR in only elderly men without T2D (P = 0.001). There was no significant difference in the RT-induced FGF-21 reduction between elderly men with and without T2D (p = 0.77, p = 0.28, respectively), but, RT caused a larger reduction in circulating myostatin in elderly men without T2D than with T2D (P = 0.007). Taken together, our results demonstrated that 12 weeks of RT induced an overall significant reduction of FGF-21 and myostatin in elderly men with and without T2D; with higher reduction of myostatin in elderly men without T2D.

From the gut to the heart: L. plantarum and inulin administration as a novel approach to control cardiac apoptosis via 5-HT2B and TrkB receptors in diabetes.

BACKGROUND & AIMS: Type 2 diabetes mellitus, as a metabolic disorder, can lead to diabetic cardiomyopathy, identified by cardiomyocyte apoptosis and myocardial fibrosis. Brain-derived neurotrophic factor (BDNF) and serotonin are two neurotransmitters that can control cardiomyocyte apoptosis and myocardial fibrosis through their cardiac receptors. In the present study, we investigated the impacts of L. plantarum and inulin supplementation on the inhibition of cardiac apoptosis and fibrosis by modulating intestinal, serum, and cardiac levels of serotonin and BDNF as well as their cardiac receptors. METHODS: Diabetes was induced by a high-fat diet and streptozotocin in male Wistar rats. Rats were divided into six groups and were supplemented with L. plantarum, inulin or their combination for 8 weeks. Finally, the rats were killed and levels of intestinal, serum, and cardiac parameters were evaluated. RESULTS: Concurrent administration of L. plantarum and inulin caused a significant rise in the expression of cardiac serotonin and BDNF receptors (P < 0.001) as well as a significant fall in cardiac interstitial and perivascular fibrosis (P < 0.001, both) and apoptosis (P = 0.01). Moreover, there was a strong correlation of cardiac 5-Hydroxytryptamine 2B (5-HT2B) and tropomyosin receptor kinase B (TrkB) receptors with interstitial/perivascular fibrosis and apoptosis (P < 0.001, both). CONCLUSIONS/INTERPRETATION: Results revealed beneficial effects of L. plantarum, inulin or their combination on intestinal, serum, and cardiac serotonin and BDNF accompanied by higher expression of their cardiac receptors and lower levels of cardiac apoptotic and fibrotic markers. It seems that L. plantarum and inulin supplementation could be considered as a novel adjunct therapy to reduce cardiac complications of type 2 diabetes mellitus.

The effect of 8 weeks of high-intensity interval training and moderate-intensity continuous training on cardiac angiogenesis factor in diabetic male rats.

The balance of pro-angiogenic and anti-angiogenic factors has a significant role in the development of diabetic cardiomyopathy. The purpose of this study was to examine the effect of 8 weeks of high-intensity interval training (HIIT) and moderate intensity continuous training (MICT) on the myocardial angiogenic factors and histological changes in male diabetic rats. Thirty-two male Wistar rats were randomly assigned into four groups: healthy non-exercised control, diabetic (D), D + HIIT, and D+ MICT groups. Diabetes type 2 was induced by a high-fat diet for 2 weeks and a single injection of streptozotocin. Following confirmation of diabetes, animals were subjected to HIIT (90 to 95% of VO2max) or MICT (50-65% of VO2max) protocols 5 days a week for 8 weeks. Western blotting was used for detection of protein expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-ß), matrix metalloproteinase-2 (MMP2), and tissue inhibitor of matrix metalloproteinase-2 (TIMP2) in the left ventricle. In addition, baseline and final blood glucose and body weight were measured. Histological changes were evaluated using H&E and Masson's trichrome staining. The results showed that exercise increased protein levels of pro-angiogenic factors while reduced anti-angiogenic factors protein levels in diabetic animals. These changes were followed by increased capillary density and reduced interstitial fibrosis in the left ventricle. Moreover, the MICT was superior to HIIT in enhancing angiogenic factors and attenuation of blood glucose and fibrosis in the diabetic rats. These findings confirm the effectiveness of exercise, particularly MICT, in the improvement of diabetic cardiomyopathy.

Hemostatic activity of aqueous extract of Myrtus communis L. leaf in topical formulation: In vivo and in vitro evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Myrtus communis L. (MC) is a well-known medicinal plant in traditional Persian medicine, which contains a large amount of phenolic compounds (mainly hydrolyzable tannins). As mentioned in ancient literature, MC was widely used to control bleeding in every part of the body. Nevertheless, there is no pharmacological study on the anti-hemorrhagic activity of this plant till now. AIM OF THE STUDY: The current in vivo and in vitro study aimed at evaluating the hemostatic activity of M. communis aqueous leaf extract (MCE) in topical formulation. MATERIALS AND METHODS: Two parameters of bleeding time and amount in tail bleeding model were measured in vivo in rats treated with MCE (1%, 2.5%, 5%, 7.5%, 10%, 15%, and 20% w/v), 5% M. communis aqueous leaf extract gel (G), tannic acid (TA) (1%, 2.5%, 5%, 7.5%, and 10%), normal saline (NS), and the Monsel's solution (MS), a commercial hemostatic agent. Also, the effect of 5% MCE and 5% TA on PT (prothrombin time) and aPTT (activated partial thromboplastin time) as well as protein precipitation and platelet aggregation were assessed in vitro. RESULTS: In the rat-tail bleeding model, bleeding time and amount significantly (P < 0.001) reduced by the application of 5% MCE solution on the cut tail compared with the NS group. The bleeding time and amount in the MS group were not significantly different from those of the 5% MCE group. Platelet microaggregates were detected by fluorescent microscope. PT and aPTT values increased >120 s and >180 s by 5% MCE, respectively. Also, protein precipitation and significant reduction in serum proteins were observed in the 5% MCE group. CONCLUSION: The current study provided new insights into the hemostatic effect of MCE, which may be partially mediated by platelet aggregation activity. Hence, it could be evaluated as the resource of new plant origin hemostatic agent.

ß-Lapachone attenuates cognitive impairment and neuroinflammation in beta-amyloid induced mouse model of Alzheimer's disease.

Oxidative stress and neuroinflammation are critically involved in amyloid beta (Aß) induced cognitive impairments. ß-Lapachone (ß-LAP) is a natural activator of NAD(P)H quinone oxidoreductase 1 (NQO1) which has antioxidant and anti-inflammatory properties.This study investigated the effect of ß-LAP administration on Aß-induced memory deficit, oxidative stress, neuroinflammation, and apoptosis cell death in the hippocampus. Forty BALB/c mice were allocated into control, sham, ß-LAP (ßL), Aß, and Aß + ßL groups. Intracerebroventricular injection of Aß1-42 was used to induce Alzheimer's disease (AD) model. Mice in the ßL and Aß + ßL groups were treated with ß-LAP (10 mg/kg, i.p) for 4 days. Results revealed that ß-LAP attenuated memory impairment in the Aß-received mice, as measured in the novel object recognition (NOR) and Barnes maze tests. Moreover, Aß resulted in inflammasome activation evident by enhanced caspase-1 immunoreactivity and interleukin-1 beta (IL-1ß) protein levels. However, ß-LAP could markedly reduce reactive oxygen species (ROS) production and down-regulate mRNA expression of NLRP3 inflammasome and protein levels of cleaved caspase 1 and IL-1ß. Additionally, ß-LAP-treated mice showed increased SIRT1 levels and NAD+/NADH ratio in the hippocampus. These results were followed by fewer number of TUNEL-positive cell, reduced hippocampal atrophy and neuronal loss in the hippocampal dentate gyrus (DG). These results indicated that the protective effect of ß-LAP against AD-associated cognitive deficits is partially through its strong antioxidant and anti-inflammatory actions.

The potential therapeutic effects of Lactobacillus plantarum and inulin on serum and testicular reproductive markers in diabetic male rats.

BACKGROUND: It is well established that diminished reproductive health is one of the notable long-term outcomes of type 2 diabetes mellitus (T2DM), especially among males. Due to the global increasing rate of T2DM and infertility, we aimed to investigate the impact of Lactobacillus plantarum (L. plantarum), inulin, and their combinatory supplementation on fertility markers as well as testicular kisspeptin and androgen receptor (AR)'s expression in diabetic male rats. METHODS: Thirty-five Male Wistar rats with Streptozotocin-induced T2DM were supplemented with L. plantarum, inulin, or their combination for 8 weeks. At the end-point, the animals were sacrificed and serum, testicular, and seminal parameters were studied. RESULTS: Administration of L. plantarum and inulin in diabetic male rats improved sperm motility and viability (P < 0.001, both) as well as testicular tissue development via increasing leydig cell number, testicular spermatid count, and diameter of seminiferous tubules (P < 0.001, all). Testicular expression of Kisspeptin was elevated by inulin supplementation (P = 0.01). L. plantarum administration increased testicular AR expression (P = 0.01). The expression of Kisspeptin showed a remarkable correlation with fertility markers (P < 0.001). CONCLUSION: Supplementation with either L. plantarum, inulin, or their combination can prevent infertility caused by T2DM in male rats via improving testicular kisspeptin and AR expression, leydig cell count, and effectively increasing epididymal sperm motility and viability.

An evaluation on potential anti-inflammatory effects of ß-lapachone.

Inflammation plays a significant role in the pathogenesis of chronic diseases. Inflammatory diseases such as bacterial diseases, Alzheimer's disease, rheumatoid arthritis, multiple sclerosis, and so on, impose huge costs on the health systems. On the other hand, some side effects have been reported for the classic drugs used to treat these diseases. Plants phytochemicals have revealed important prospects in the handling and controlling of human diseases. ß-lapachone, is a derivative of the naturally occurring element lapachol, from Tabebuia avellanedae and its anti-inflammatory effects have been reported in several reports. This review summarized the evidence from cell and animal studies supporting the anti-inflammatory role of ß-lapachone and discussed its potential mechanisms.

Physical and cognitive training attenuate hippocampal ischemia-induced memory impairments in rat.

The present study aimed to evaluate the preventive role of physical and cognitive training separately or in combination on memory dysfunction, inflammatory factors and apoptotic markers in the hippocampal-ischemia model of rat. The ischemia model was established by infusion of endothelin-1 (ET-1) into the animal's hippocampus using stereotaxic surgery. Physical, cognitive and combination training groups exposed to voluntary running wheel exercise or modified Barnes maze cognitive task or combination of this interventions for 4 weeks, respectively. Next, Morris water maze (MWM) and novel object recognition (NOR) tasks were used to assess recognition and spatial learning and memories. Western blotting was used to evaluate the protein levels of Nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-alpha receptor 1 (TNFR1), cytochrome c, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 in the hippocampal tissue. Hippocampal ischemia significantly impaired recognition and spatial learning and memory with an increase of inflammatory and apoptotic proteins in the hippocampus tissue. Interventions in combination or separately significantly improved performance of ischemia-received animals in memory tasks. Furthermore, both physical and cognitive paradigms also reduced inflammatory and apoptotic factors in the hippocampus of ischemia-received rats. These findings indicate that physical and cognitive training separately or in combination attenuates the deleterious effect of ischemia on cognition through its anti-inflammatory and anti-apoptotic properties.

Cardioprotective effect of Rosa canina L. methanolic extract on heat shock induced cardiomyocyte injury: An experimental study.

Introduction: Overexposure to heat conditions can affect the functioning of the cardiovascular system and may promote cardiovascular disorders. Heat shock induced myocardial injury via increasing endoplasmic reticulum response-mediated apoptosis. This study investigated the impact of pretreatment with Rosa canina (RC), a natural antioxidant, on myocardial damage induced by heat stress exposure and underlying mechanisms in cardiomyocytes in rats. Methods: Sixty adult male Wistar rats were allocated into five groups, including Control: received normal saline (NS), Heat Stress (HS), and HS+RC groups. Animals in the HS groups were subjected to heat stress (43 ºC) for 15 minutes once a day for two weeks. Animals in the HS+RC groups received three doses of RC (250, 500, and 1000 mg/mL) one hour before being subjected to heat shock. The endoplasmic reticulum (ER) transmembrane kinases, including PKR-like endoplasmic reticulum kinase (PERK), immunoreactivity of CCAAT/enhancer-binding protein homologous protein (CHOP), and eukaryotic translation initiation factor 2-alpha (eIF2α) as well as caspase 8 were detected by Western blot. The levels of reactive oxygen species (ROS) were assessed. Moreover, histopathological changes and apoptosis were also assayed in the heart tissue by using histopathological and TUNEL assays. Results: Heat exposure increased the level of ROS and induced oxidative damage in the heart tissue. The results demonstrated that RC administration decreased the overproduction of ROS induced by heat stress in cardiomyocytes. Moreover, heat stress up regulated the expression of p-PERK, p-eIF2α,and CHOP protein while pretreatment with RC decreased expression of ER stress-related markers in cardiomyocytes. Besides, RC diminished heat stress-induced cellular damage and apoptosis associated with inhibition of caspase 8 activation, a pro-apoptotic protein in cardiomyocytes. Conclusion: These findings indicate that RC exerts a protective effect on heart tissue, at least in part,through inactivation of PERK/eIF2α/CHOP pathway or inhibition of ER stress and oxidative stress triggeredapoptosis in cardiomyocytes induced by heat stress.

Lactobacillus plantarum And Inulin: Therapeutic Agents to Enhance Cardiac Ob Receptor Expression and Suppress Cardiac Apoptosis in Type 2 Diabetic Rats.

BACKGROUND: T2DM may cause increased levels of oxidative stress and cardiac apoptosis through elevated blood glucose. The present study investigated the effects of Lactobacillus plantarum (L. plantarum) as a probiotic strain and inulin as a prebiotic supplement on cardiac oxidative stress and apoptotic markers in type 2 diabetes mellitus (T2DM) rats. METHODS: A high-fat diet and a low dose of streptozotocin were used to induce type 2 diabetes. The rats were divided into six groups which were supplemented with L. plantarum, inulin, or their combination for 8 weeks. RESULTS: The results showed improved activity of cardiac antioxidant parameters including total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (P < 0.001, P < 0.01, and P < 0.01, respectively) and decreased level of cardiac malondialdehyde (MDA) concentration (P < 0.05). These changes were accompanied with increased protein expression of cardiac obesity receptor (Ob-R) (P = 0.05) and reduced apoptotic markers such as tumor necrosis factor-alpha (TNF-α), Fas ligand (FasL), and caspase proteins (P < 0.001, P = 0.003, and P < 0.01, respectively) in T2DM rats after concurrent L. plantarum and inulin supplementation. Moreover, a remarkable correlation of cardiac Ob-R and oxidative stress parameters with cardiac apoptotic markers was observed (P < 0.01). CONCLUSION: The concurrent use of L. plantarum and inulin seems to be beneficial, as they can lead to decreased heart complications of T2DM via reducing cardiac apoptotic markers.