Impact of combined alpha-lipoic acid and mitoquinone supplementation on myocardial infarction in aged rats: Heart performance and molecular mechanisms.

BACKGROUND: This study aimed to investigate the effects of combined alpha-lipoic acid (ALA) and mitoquinone (Mito Q) supplementation on cardiac function and the underlying mechanisms in aged rats with myocardial infarction (MI). METHODS: The aged rats underwent left anterior descending artery (LADA) occlusion for 30 min, followed by reperfusion for 24 h. ALA (100 mg/kg, gavage) and Mito Q (10 mg/kg, IP) were administered daily for two weeks before ischemia. Cardiac function, inflammatory, and apoptotic markers were evaluated 24 h after ischemia. RESULTS: The results of this study indicated that the administration of the combination of ALA and Mito Q significantly improved cardiac function. This improvement was linked to a reduction in the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß (P < 0.001) and apoptotic markers (Bax, caspase-3, and Cyt-c), as well as a decrease in the percentage of TUNEL-positive cells (P < 0.001). CONCLUSION: The study revealed that combined intervention synergistically mitigated cardiac dysfunction by suppressing inflammatory and apoptotic pathways in aged rats with MI. Further research is needed to validate the potential of ALA and Mito Q as therapeutic options for elderly people at risk of heart attacks.

Pre-Ischemic Oxytocin Treatment Alleviated Neuronal Injury via Suppressing NF-κB, MMP-9, and Apoptosis Regulator Proteins in A Mice Model of Stroke.

Objective: This study was designed to determine the effects of pre-ischemic administration of oxytocin (OXT) on neuronal injury and possible molecular mechanisms in a mice model of stroke. Materials and Methods: In this experimental study, stroke was induced in the mice by middle cerebral artery occlusion (MCAO) for 60 minutes and 24 hours of reperfusion. OXT was given as intranasal daily for 7 consecutive days before ischemic stroke. Neuronal damage, spatial memory, and the expression levels of nuclear factor-kappa B (NF-κB), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), brain-derived neurotrophic factor (BDNF) and apoptosis were assessed 24 hours after stroke. Results: Pre-ischemic treatment with OXT significantly reduced the infarct size (P<0.01); but did not recover the neurological and spatial memory dysfunction (P>0.05). Moreover, OXT treatment considerably decreased the expressions of NF-κB, TNF-α, IL-1ß, and MMP-9 (P<0.001) and enhanced the level of BDNF protein. OXT treatment also significantly downregulated Bax expression and overexpressed Bcl-2 proteins. Conclusion: The finding of this study indicated that administration of OXT before ischemia could limit brain injury by inhibiting MMP-9 expression, apoptosis, inflammatory signaling pathways, and an increase in the BDNF protein level. We suggested that OXT may be potentially useful in the prevention and/or reducing the risk of the cerebral stroke attack, and could be offered as a new prevention option in the clinics.

Neuroprotective Effects of Chemerin on a Mouse Stroke Model: Behavioral and Molecular Dimensions.

The present study was conducted to investigate the effects of different doses of recombinant human Chemerin (rhChemerin) on brain damage, spatial memory, blood-brain barrier (BBB) disruption and cellular and molecular mechanisms in a mouse stroke model. The mouse stroke model was developed by blocking the middle cerebral artery for 1 h and performing reperfusion for 23 h. Immediately, one and three hours after the stroke, 200, 400 and 800 ng/mouse of intranasal rhChemerin was administered. Neuronal and BBB damage, spatial memory and neurological performance were examined 24 h after the stroke. Western blotting and immunofluorescence were utilized to determine the effects of rhChemerin on the expressions of nuclear factor kappa B (NF-κB), pro-inflammatory cytokines such as TNF-α and IL-1ß, anti-inflammatory cytokines such as IL-10 and TGF-ß and vascular endothelial growth factor (VEGF). Administering 400 and 800 ng/mouse of rhChemerin in the mice immediately and one hour after ischemia minimized the infarct size, BBB opening, spatial memory and neurological impairment (P < 0.001). Furthermore, 800 ng/mouse of rhChemerin significantly diminished terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive (apoptotic) cells, suppressed the expressions of NF-kB, TNF-α and IL-1ß and upregulated IL-10 and VEGF in the cortex and hippocampus of the mice. The present findings showed that rhChemerin administered immediately and one hour after stroke alleviates neuronal and BBB injures and improves spatial memory. These effects of rhChemerin may be mediated by inhibiting inflammatory pathways and apoptotic machinery.

Prophylactic effect of intranasal oxytocin on brain damage and neurological disorders in global cerebral ischemia in mice.

OBJECTIVES: A few experimental studies have shown the therapeutic effects of oxytocin on focal cerebral ischemia. In this study, the prophylactic effect of intranasal oxytocin on brain damage was investigated in a cerebral ischemic model. MATERIALS AND METHODS: Intranasal oxytocin (8 IU/per mouse) was prescribed daily for one week. Cerebral ischemia was performed through bilateral common carotid artery occlusion (BCCAO) for 20 min and then blood flow was restored for 24 hr. Finally, neurological disorders, spatial learning and memory, neuronal death, and neuronal apoptosis were assessed in CA1, CA3, and dentate gyrus. Also, levels of interleukin-1ß (IL-1ß) and Tumor necrosis factor-alpha (TNFα) were measured in the hippocampus. RESULTS: Induction of global ischemia leads to neurological disorders and impairment of spatial learning and memory that are improved by pre-treatment with oxytocin (P<0.01). Cresyl violet staining showed that pretreatment with oxytocin significantly reduced the number of dead nerve cells in CA1, CA3, and dentate gyrus by 40.7, 32, and 34.3%, respectively. Also, positive TUNEL cells in CA1, CA3, and dental gyrus decreased by 15, 30, and 27%, respectively. In addition, levels of TNFα and IL-1ß, which were extensively increased in ischemic mice, were significantly reduced with oxytocin pre-treatment. CONCLUSION: Pre-treatment of oxytocin reduces ischemic damage and improves neurological function and spatial memory. The neuroprotective effect of oxytocin is mediated by a decrease in cell death, apoptosis, and inflammatory mediators TNFα and IL-1ß. Pre-treatment with oxytocin may be useful in people who are prone to stroke.

Oxytocin Reduces Brain Injury and Maintains Blood-Brain Barrier Integrity After Ischemic Stroke in Mice.

The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Brain injury, BBB integrity, and spatial memory were evaluated by standard methods. Changes in the expression of nuclear factor-kappa B (NF-κB), and TUNEL positive cell were detected by immunohistochemistry. The levels of vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF) proteins were determined by western blotting and ELISA methods. OXT at doses of 4 and 8 IU/per mouse reduced the infarct size by 42% and 52%, respectively, and improved spatial memory function (p < 0.001). OXT (8 IU/per mouse) significantly reduced brain edema, BBB disruption and upregulated the AQP4 expression (p < 0.001). Finally, OXT significantly diminished the number of apoptotic, NF-κB positive cells and enhanced the expression of BDNF and VEGF proteins in the brain tissue (p < 0.001). These findings provide important evidences that OXT significantly suppresses neuronal damage in the early stage of stroke by inhibiting apoptotic and NF-κB signaling pathway, increasing the expression of VEGF, AQP4 and BDNF proteins and reducing the BBB leakage.

Effect of stem cells-based therapy on astrogliosis in stroke subjected-mice.

This study was planned to continue our previous study to assess effect of combination therapy bone marrow stromal cells (BMSCs) with exercise (EX) and triiodothyronine (T3) on stroke-induced astrogliosis in mice. Stroke subjected-mice were divided into five monotherapy groups including sham, control, BMSCs, EX and T3; and three combination therapy groups including BMSCs + EX, BMSCs + T3 and BMSCs + EX + T3. Astrogliosis was assessed in ipsilateral hemisphere at day 7 after MCAO. Combination therapy BMSCs with EX and T3 could significantly decrease stroke-induced astrogliosis. However, monotherapy with BMSCs or EX also improved changes of glial fibrillary acidic protein (GFAP)-positive cells following stroke. Combination therapy BMSCs with EX and T3 didn't have any added effect on astrogliosis compared to monotherapy with BMSCs or EX. With comparing the present findings with the results of neurobehavioral functioning in our earlier study, it seems that decrease of astrogliosis could be helpful for stroke recovery.

Chronic treatment with apelin, losartan and their combination reduces myocardial infarct size and improves cardiac mechanical function.

The renin-angiotensin system (RAS) has a deleterious and apelin/APJ system has protective effect on the ischaemic heart. The collaboration between these systems in the pathophysiology of myocardial infarction is not clear. We determined the effect of chronic pretreatment with apelin, losartan and their combination on ischaemia-reperfusion (IR) injury in the isolated perfused rat heart and on the expression of apelin-13 receptor (APJ) and angiotensin type 1 receptor (AT1R) in the myocardium. During 5 days before the induction of IR, saline (vehicle), apelin-13 (Apl), F13A (apelin antagonist), losartan (Los, AT1R antagonist) and the combination of Apl and Los were administered intraperitoneally in rats. Ischaemia was induced by left anterior descending (LAD) artery occlusion for 30 minutes followed by reperfusion for 55 minutes in the Langendorff isolated heart perfusion system. Pretreatment with Apl, Los and the combination of Apl + Los significantly reduced infarct size by about 30, 33 and 48 percent respectively; and significantly improved the left ventricular function indices such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) and rate pressure product (RPP). IR increased AT1R protein level but it did not change APJ significantly. AT1R expression was reduced in groups treated with Apl, Los and Apl + Los. Findings showed that chronic pretreatment with apelin along with AT1R antagonist had more protective effects against IR injury. Combination therapy may diminish the risk of IR-induced heart damage, by reducing AT1R expression, in the heart of patients with coronary artery disease that are at the risk of MI and reperfusion injury.

Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model.

Probiotics are referred to species of living microscopic organisms may help conserve the normal balance of the digestive system and/or manage diseases. A number of autoimmune, psychiatric, cardiovascular and cerebrovascular disorders may be associated with the imbalance of gut microbiota. This study examines the effect of 21 days consumption of multistrain probiotics on hippocampus injury, spatial and learning memory and some potential molecular mechanisms in a mouse model with cerebral hypoperfusion. Cerebral hypoperfusion was established in the mouse model by bilateral common carotid artery occlusion (BCCAO) for 20 min and 24 h reperfusion. Mixtures of several probiotic bacteria at concentrations of 107, 108 and 109 CFU/day were orally administrated for 3 weeks before the BCCAO. Spatial and learning memory, histological damage and apoptosis were assessed in the CA1, CA3 and dentate gyrus (DG) of the hippocampus 24 h after ischemia. The malondialdehyde (MDA) content and brain-derived neurotrophic factor (BDNF) level were measured by ELISA technique. Prophylactic of probiotic considerably reduced the number of apoptotic cells and neuronal death in the CA1, CA3 and DG of the hippocampus at all three concentrations (P < 0.001). In addition, probiotics reduced spatial memory impairment and neurological dysfunction only at the 109-CFU/day (P < 0.01). Nonetheless, probiotics did not change the levels of BDNF and MDA in the hippocampus (P > 0.05). According to the findings, the daily prophylactic ingestion of probiotics reduced hippocampus damage and prevented the spatial learning and memory deficit by suppressing apoptosis in the mouse model with cerebral hypoperfusion. Probiotic supplementation may be suggested as a useful preventive dietary strategy for groups susceptible to cerebrovascular diseases.

Occurrence of priapism after transient right MCAO in Swiss albino mice.

Introduction: There are few reports about sexual problems in animal models after stroke. The aim of this paper is to report the occurrence of priapism after right MCAO in Swiss albino mice. In addition, we compared neurological score and apoptosis between the priapism-affected and unaffected mice. Methods: Swiss albino mice were subjected to 45 min' MCAO and 7 days' reperfusion. Mice were observed before MCAO, then daily for 7 days to assess priapism. Neurological status and apoptosis (TUNEL assay) were assessed and compared in priapism and non-priapism mice. Results: The results showed that the incidence of priapism after MCAO in Swiss albino mice were 65%. Priapism was detectable often at day 2 after stroke. Priapism-affected group had more severe behavioural deficits after stroke compared to non-priapism stroke mice. Conclusion: Priapism after right MCAO is not rare in albino mice and could be considered as a marker of stroke severity. Further studies are needed to assess the incidence of priapism after stroke in other animal species used for stroke studies such as rat.

Bone Marrow Stromal Cells With Exercise and Thyroid Hormone Effect on Post-Stroke Injuries in Middle-aged Mice.

INTRODUCTION: Based on our previous findings, the treatment of stem cells alone or in combination with thyroid hormone (T3) and mild exercise could effectively reduce the risk of stroke damage in young mice. However, it is unclear whether this treatment is effective in aged or middle-aged mice. Therefore, this study designed to assess whether combination of Bone Marrow Stromal Cells (BMSCs) with T3 and mild treadmill exercise can decrease stroke complications in middle-aged mice. METHODS: Under laser Doppler flowmetry monitoring, transient focal cerebral ischemia was produced by right Middle Cerebral Artery Occlusion (MCAO) for 45 min followed by 7 days of reperfusion in middle-aged mice. BMSCs (1×105) were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of triiodothyronine (T3) (20 µg/100 g/d SC) and 6 days of running on a treadmill. Infarct size, neurological function, apoptotic cells and expression levels of Glial Fibrillary Acidic Protein (GFAP) were evaluated 1 week after stroke. RESULTS: Post-ischemic treatment with BMSCs or with T3 and or mild treadmill exercise alone or in combination did not significantly change neurological function, infarct size, and apoptotic cells 7 days after ischemia in middle-aged mice (P>0.05). However, the expression of GFAP significantly reduced after treatment with BMSCs and or T3 (P<0.01). CONCLUSION: Our findings indicate that post-stroke treatment BMSCs with exercise and thyroid hormone cannot reverse neuronal damage 7 days after ischemia in middle-aged mice. These findings further support that age is an important variable in stroke treatment.

The Effects of Mouse Recombinant Resistin on mRNA Expression of Proinflammatory and Anti-Inflammatory Cytokines and Heat Shock Protein-70 in Experimental Stroke Model.

BACKGROUND: Our recent research showed that resistin has a neuroprotective effect against stroke-induced injury through suppressing apoptosis and oxidative stress. However, the molecular mechanism of neuroprotection of resistin is unclear. This work was designed to examine the effect of mouse recombinant resistin on mRNA expression of Tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-10 (IL-10), Transforming growth factor-ß1 (TGF- ß1), and Heat shock protein-70 (HSP-70) in mouse model of stroke. MATERIALS AND METHODS: Transient focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) in mice. TNF-α, IL-1ß, IL-10, TGF-ß1, and HSP-70 mRNA were detected at sham (0 hour), 3 hours, 6 hours, 12 hours, and 24 hours after MCAO using real-time QRT-PCR method. Moreover, animals were treated with resistin at the dose of 400ng/mouse at the commencement of MCAO, and mRNA expression of the cytokines and HSP-70 was measured 24 hours after MCAO. RESULTS: Tumor necrosis factor-α and IL-1ß mRNA expression markedly increased at 12-hour time point and then returned to the basal level at 24 hours after MCAO; but HSP-70 mRNA expression increased at 24-hour time point. Furthermore, resistin (400 ng/mouse) significantly increased TGF-ß1 and IL-10 and decreased HSP-70 gene expression at 24 hours after MCAO. CONCLUSIONS: Our findings revealed that a molecular mechanism of attenuating ischemic damage by resistin administration probably is increased mRNA expression of anti-inflammatory cytokines. However, applying resistin in the clinical settings for the treatment of stroke deserves further researches in the future.

Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke.

Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood-brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0.1, 0.5, 2.5, 7.5, and 15 µg/kg, intracerebroventricularly (ICV), on the MCAO beginning. Neurological outcomes, infarct size, brain edema and BBB permeability were evaluated by modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans blue (EB) extravasation methods, respectively, at 24 h after ischemia. Apoptotic cells and BDNF protein were detected by TUNEL assay and immunohistochemistry techniques. The levels of Bcl-2, Bax and caspase-3 proteins were measured by immunoblotting technique. ICV irisin administration at doses of 0.5, 2.5, 7.5 and 15 µg/kg, significantly reduced infarct size, whereas only in 7.5 and 15 µg/kg improved neurological outcome (P < 0.001). Treatment with irisin (7.5 µg/kg) reduced brain edema (P < 0.001) without changing BBB permeability (P > 0.05). Additionally, irisin (7.5 µg/kg) significantly diminished apoptotic cells and increased BDNF immunoreactivity in the ischemic brain cortex (P < 0.004). Irisin administration significantly downregulated the Bax and caspase-3 expression and upregulated the Bcl-2 protein. The present study indicated that irisin attenuates brain damage via reducing apoptosis and increasing BDNF protein of brain cortex in the experimental model of stroke in mice.

Effects of the Oral Ingestion of Probiotics on Brain Damage in a Transient Model of Focal Cerebral Ischemia in Mice.

BACKGROUND: Probiotics are microorganisms that may influence brain function via altering brain neurochemistry. New research evidence suggests that probiotic bacteria might protect tissue damage through diminishing the production of free radicals and/or inflammatory cytokines. Therefore, this study was designed to evaluate the effects of probiotic bacteria on the prevention or reduction of brain damage in an experimental model of stroke in mice. METHODS: In this study, 30 male BLC57 mice were randomly divided into 6 equal groups. Focal cerebral ischemia was induced via middle cerebral artery occlusion for 45 minutes, followed by 24 hours of reperfusion, in the mice. Probiotics at a concentration of 107 CFU/mL were administered by oral gavage daily for 14 days before ischemia. Infarct size, neurological outcome, and biochemical markers were measured 24 hours after brain ischemia. Statistical analysis were performed using the one-way ANOVA and/or Kruskal-Wallis ANOVA on rank by Sigma Stat (2.0; Jandel Scientific) software. RESULTS: Our results indicated that pretreatment with probiotics significantly reduced infarct size by 52% (P=0.001) but could not improve neurological function (P=0.26). Moreover, the administration of probiotics significantly decreased the malondialdehyde content (P=0.001) and the tumor necrosis factor-alpha level (P=0.004) in the ischemic brain tissue. CONCLUSION: The findings of the present study showed that probiotic supplements might be useful in the prevention or attenuation of brain ischemic injury in patients at risk of stroke. Probiotics may open new therapeutic alternatives for the prevention of stroke. More preclinical and clinical studies are, however, needed to clarify their efficacy in cerebral stroke.

Neuroprotective nature of adipokine resistin in the early stages of focal cerebral ischemia in a stroke mouse model.

New evidence suggests that resistin may have a therapeutic potential effect in management of neurodegenerative disease; but its role in the pathophysiology of stroke-induced injuries is not understood. However, further investigations are required to elucidate the effect of resistin and explore its possible molecular mechanisms on the ischemic reperfusion injury. Transient focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) in mice. Animal treated with resistin at doses of 25, 50, 100, 200, and 400 ng/mouse, on the MCAO commencement. Neurological function, infarct size, brain edema and Blood-brain barrier (BBB) disruption were measured. Additionally, content of malondialdehyde (MDA), TUNEL-positive cells and apoptosis-related proteins were assessed by immunohistochemistry and western blot techniques. Resistin mRNA was detected at 3 h, 6 h, 12 h and 24 h after MCAO using real-time QRT-PCR method. Central administration of resistin only at doses of 200 and 400 ng/mouse considerably reduced the infarct size and promoted neurological function (p < 0.001). In addition, resistin (400 ng/mouse) significantly decreased brain edema (p < 0.001), evans blue (EB) leakage (p < 0.05), MDA content (p < 0.005), apoptotic cells and apoptosis-related proteins (p < 0.001). Resistin mRNA expression markedly increased at 12-h time point and then returned to basal level at 24 h after MCAO. Our findings revealed that treatment with resistin could attenuate ischemic damage in a dose-dependent approach via suppressing apoptosis and oxidative stress. Application of resistin in clinical settings to treat stroke and brain ischemia warrants further research.

Effects of the combined treatment of bone marrow stromal cells with mild exercise and thyroid hormone on brain damage and apoptosis in a mouse focal cerebral ischemia model.

This study examined whether post-stroke bone marrow stromal cells (BMSCs) therapy combined with exercise (EX) and/or thyroid hormone (TH) could reduce brain damage in an experimental ischemic stroke in mice. Focal cerebral ischemia was induced under Laser Doppler Flowmetry (LDF) guide by 45 min of middle cerebral artery occlusion (MCAO), followed by 7 days of reperfusion in albino mice. BMSCs were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of T3 (20 µg/100 g weight S.C) and 6 days of running on a treadmill. Infarct size, neurobehavioral test, TUNEL and BrdU positive cells were evaluated at 7 days after MCAO. Treatment with BMSCs and mild EX alone significantly reduced the infarct volume by 23% and 44%, respectively (both, p < 0.001). The BMSCs + TH, BMSCs + EX, and BMSCs + EX + TH combination therapies significantly reduced the infarct volume by 26%, 51%, and 70%, respectively (all, p < 0.001). A significant improvement in the neurobehavioral functioning was observed in the EX, BMSCs + EX, and BMSCs + EX+ TH groups (p < 0.001). The number of TUNEL-positive cells (a marker of apoptosis) was significantly reduced in the EX, BMSCs, BMSCs + EX, BMSCs + TH, and BMSCs + EX + TH groups (all, p < 0.001). Moreover, the combination therapy considerably increased BrdU-labeled cells in the subventricular zone (SVZ) (p < 0.01). Our findings indicated that the combined treatment of BMSCs with mild EX and TH more efficiently reduces the cerebral infarct size after stroke. More likely, these effects mediate via enchaining generation of new neuronal cells and the attenuation of apoptosis in ischemia stroke in young mice.

Lavandula Reduces Heart Injury via Attenuating Tumor Necrosis Factor-Alpha and Oxidative Stress in A Rat Model of Infarct-Like Myocardial Injury.

OBJECTIVE: Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated. MATERIALS AND METHODS: In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury (MI). The carotid artery and left ventricle were cannulated to record arterial blood pressure (BP) and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha (TNF-α) level were evaluated. RESULTS: Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-α and troponin I in heart tissue (P<0.001). Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-α. In addition, it improved cardiac function and antioxidant enzyme activity (P<0.01). CONCLUSION: Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease.

The Effect of Oral Consumption of Probiotics in Prevention of Heart Injury in a Rat Myocardial Infarction Model: a Histopathological, Hemodynamic and Biochemical Evaluation.

BACKGROUND: Despite the emerging evidence on beneficial effects of probiotics on the cardiovascular system, their impact on the management of ischemic heart diseases and its possible mechanism have not been elucidated. METHODS: Four viable probiotics bacterial strains, including Bifidobacterium breve, Lactobacillus casei, Lactobacillus bulgaricus and Lactobacillus acidophilus, at the concentrations of 2×106 colony-forming units/ml were orally administered to the rats daily for 14 days before the induction of infarct-like myocardial injury using isoproterenol. Subsequently, 24 h after myocardial injury, the right carotid artery and the left ventricle were catheterized for recording blood pressure and cardiac parameters. At the end of the experiment, the heart was removed for the evaluation of histopathological and biochemical parameters, as well as tumor necrosis factor-alpha (TNF-α) assay. RESULTS: The induction of acute myocardial injury resulted in significant (P≤0.01) left ventricular (LV) dysfunction, as shown by an increase in LV end-diastolic pressure and a decrease in LV dp/dt max, LV dp/dt min, LV systolic pressure, and blood pressure, as compared with normal rats. Pretreatment with viable probiotics significantly reduced lipid peroxidation and TNF-α level and improved cardiac function (P<0.01). CONCLUSION: This study shows that viable probiotics have a cardioprotective effect on infarct-like myocardial injury through suppressing TNF-α and oxidative stress damage in a rat model. Probiotic supplements may be used as a new option for prophylaxis in patients at the risk of ischemic heart disease in future.

Effect of the Inhibition of Hydrogen Sulfide Synthesis on Ischemic Injury and Oxidative Stress Biomarkers in a Transient Model of Focal Cerebral Ischemia in Rats.

OBJECTIVE: Hydrogen sulfide (H2S) plays multiple roles in the function of the central nervous system in physiological and pathological conditions, such as cerebral ischemia. Recent studies have reported controversial results about the role of H2S in cerebral ischemia. The aim of this study was to evaluate the effects of amino-oxyacetic acid (AOAA), an inhibitor of H2S synthesis, on ischemic injury in an experimental model of stroke. METHODS: Using laser Doppler monitoring, cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAO) for 1 hour in rats. AOAA (.025, .05, .1, and .5 mmol/kg intraperitoneally [i.p.]) was injected at the beginning of MCAO. Infarct volume, cerebral edema, and activity of antioxidant enzymes were measured using the standard methods 24 hours after ischemia. RESULTS: The administration of AOAA at doses .025, .05, and .1 mmol/kg significantly reduced the infarct volume (P < .001). Furthermore, .025 and .05 mmol/kg of AOAA significantly reduced brain edema and improved the neurological outcome (P < .001). The administration of AOAA did not significantly change the malondialdehyde content, activities of superoxide dismutase, or glutathione peroxidase antioxidant enzymes in the brain tissue (P > .05). CONCLUSION: The results showed that AOAA administered at a low dose has protective effects; however, at higher doses it did not exert any protective effect against cerebral ischemia and even worsened the ischemic injury. This finding suggests that H2S might be both beneficial and harmful in cerebral ischemic injury depending on its concentration in transient model of focal cerebral ischemia.

Investigation of changes in apelin receptor mRNA and protein expression in the myocardium and aorta of rats with two-kidney, one-clip (2K1C) Goldblatt hypertension

Experimental and clinical evidences suggest that apelin and its receptor APJ are involved in the pathogenesis of cardiovascular complications. However, the role of apelin/APJ in hypertension is not sufficiently understood. Because chronic kidney diseases lead to hypertension and cardiac failure, we investigated the changes in apelin receptor gene expression in the myocardium and aorta of rat models of kidney disease hypertension. Two-kidney, one-clip (2K1C) hypertension was produced by placing a clip around the renal artery. Four and 16 weeks later, blood pressure, left ventricular end-diastolic pressure (LVEDP), serum apelin, and angiotensin II were measured. The messenger RNA (mRNA) and protein of APJ were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Chronic hypertensive rats had approximately 10 times higher LVEDP (P < 0.001). 2K1C decreased serum apelin from 220 ± 11 to 170 ± 10 pg/mL in 16 weeks (P < 0.05). The mRNA expression of APJ significantly decreased in the heart and aorta at 4 weeks. At 16 weeks, the reduction was not significant in the heart but was significant in the aorta. At 4 weeks, the expression of the APJ protein significantly decreased in the heart but not in the aorta. At 16 weeks, APJ protein was significantly decreased only in the aorta. Reduction of serum apelin and downregulation of apelin receptors in both the heart and aorta may play a role in the pathophysiology of hypertension and cardiac failure in 2K1C hypertensive rats

Investigation of changes in apelin receptor mRNA and protein expression in the myocardium and aorta of rats with two-kidney, one-clip (2K1C) Goldblatt hypertension.

Experimental and clinical evidences suggest that apelin and its receptor APJ are involved in the pathogenesis of cardiovascular complications. However, the role of apelin/APJ in hypertension is not sufficiently understood. Because chronic kidney diseases lead to hypertension and cardiac failure, we investigated the changes in apelin receptor gene expression in the myocardium and aorta of rat models of kidney disease hypertension. Two-kidney, one-clip (2K1C) hypertension was produced by placing a clip around the renal artery. Four and 16 weeks later, blood pressure, left ventricular end-diastolic pressure (LVEDP), serum apelin, and angiotensin II were measured. The messenger RNA (mRNA) and protein of APJ were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Chronic hypertensive rats had approximately 10 times higher LVEDP (P < 0.001). 2K1C decreased serum apelin from 220 ± 11 to 170 ± 10 pg/mL in 16 weeks (P < 0.05). The mRNA expression of APJ significantly decreased in the heart and aorta at 4 weeks. At 16 weeks, the reduction was not significant in the heart but was significant in the aorta. At 4 weeks, the expression of the APJ protein significantly decreased in the heart but not in the aorta. At 16 weeks, APJ protein was significantly decreased only in the aorta. Reduction of serum apelin and downregulation of apelin receptors in both the heart and aorta may play a role in the pathophysiology of hypertension and cardiac failure in 2K1C hypertensive rats.