The therapeutic potential of Melissa officinalis L. hydroalcoholic extract and rosmarinic acid in a rat asthmatic model: A study on anti-inflammatory and antioxidant effects.

Objective: The article studies how Melissa officinalis L. extract and rosmarinic acid (RA) affect lung inflammation, pathology, and oxidative stress in rats with ovalbumin-induced asthma. Materials and Methods: Asthma was induced in rats using ovalbumin injection and inhalation. The study assessed lung inflammation, pathological changes, and oxidative stress in control, untreated asthmatic rats and three treatment groups. These groups received M. officinalis extract (50, 100, 200 mg/kg), RA (0.5, 1, 2 mg/kg), or dexamethasone (Dex) 1 mg/kg. Results: In the sensitized group, white blood cell counts, malondialdehyde, and nitrite levels increased significantly, while thiol levels and the activity of superoxide dismutase and catalase decreased (p<0.001). However, all treatment groups with the extract, RA, and Dex showed a significant reduction in total white blood cells, eosinophils, monocytes, malondialdehyde, and nitrite levels compared to the asthma group (p<0.001 in all groups). Thiol levels and catalase and superoxide dismutase activity were significantly higher in all treated groups with RA and high extract doses (p<0.001). Lung pathological changes were also significantly less severe in the treated groups with dexamethasone, plant extract, and RA compared to the asthma group (p<0.05 to p<0.001). Conclusion: This study showed that M. officinalis and RA have antioxidant and anti-inflammatory effects in an animal asthma model, suggesting their potential for treating asthma symptoms.

Antimicrobial Peptides as a Promising Therapeutic Strategy for Neisseria Infections.

Antibiotic resistance is already widespread in the world, and it has become a great health problem. Therefore, comprehensive efforts are needed to minimize the resistance. The exploration of alternative therapies may offer a more targeted approach with less susceptibility to resistance. Even though antimicrobial peptides (AMPs) have been introduced as emerging antibiotic sources, they are not widely discussed in the literature. Since Neisseria infections show resistance to different types of antibiotics, the purpose of this review was to discuss the currently investigated AMPs with anti-Neisseria properties. In the present review, we provide an overview of 24 AMPs with in vitro anti-Neisseria properties.

Sex-specific endothelial dysfunction induced by high-cholesterol diet in rats: The role of protein tyrosine kinase and nitric oxide.

BACKGROUND AND AIMS: Atherosclerosis is a chronic process playing a crucial role in the pathogenesis of cardiovascular disease. Sex-specific differences in the incidence of atherosclerosis indicate that estrogen has a protective effect on the cardiovascular disease. However, the role of sex on endothelium responses in animal models of high cholesterol (HC) diet-induced atherosclerosis has not been fully investigated. This study was aimed to investigate vascular responses in HC-fed rats. METHODS AND RESULTS: Male and female Sprague rats (12-week-old) were treated with either a standard diet (n = 12 of each sex) or an HC enriched diet (n = 12 of each sex) containing 2% cholesterol for 24 weeks. HC treated animals (both sexes) showed increased levels of total cholesterol, LDL-cholesterol, triglyceride and blood pressure (BP) compared to control rats. While the BP of control rats (both sexes) was increased following aminoguanidine administration (AG, 100 mg/kg i.p.), it was not changed in HC animals (both sexes). The hypotensive effect of acetylcholine was significantly impaired in male HC-treated rats. In vitro experiments demonstrated that aortic rings from HC group (both sexes) had an increased contractile response to phenylephrine and a decreased vasodilatory response to acetylcholine. The vasorelaxant effect of acetylcholine in HC rats (only male) was improved by applying 10-5 M genistein (tyrosine kinase inhibitor) or AG. CONCLUSION: HC diet alters endothelium function through Nitric oxide (NO) and tyrosine kinase pathways in male rats.

Therapeutic potential of Ferula foetida(Bunge) Regel on gastric ulcer model in rats.

The plant Ferula foetida(Bunge) Regel (FFBR) has a long history in Asian traditional medicine. This study aimed to evaluate the ulcer healing potential of FFBR umbel ethanolic extract on acetic acid-induced chronic gastric ulcer in rats. First, the gastric ulcer model was imitated by serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed by ethanolic extract of FFBR umbel (100 mg/kg, 200 mg/kg, and 300 mg/kg), omeprazole (40 mg/kg), or saline for 12 days. Eventually, on the 13th day, animals were sacrificed, and their stomachs were taken out. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. In addition, the expression of NF-κB p65 was investigated by immunohistochemistry. Compared to the untreated rats with gastric ulcer, FFBR extract significantly decreased ulcer area even superior to omeprazole in a dose-dependent manner. Moreover, histological examination revealed that the extract (300 mg/kg) accelerated the epithelialization and differentiation of proliferative cells to mucosal tissue. The FFBR extract (300 mg/kg) increased tissue levels of VEGF and PGE2, but it did not affect MDA levels in rats with gastric ulcers. FFBR treatment (all doses) could significantly inhibit the expression of NF-κB p65 in gastric tissue. Taken together, experimental findings suggested that FFBR could accelerate the healing process of gastric ulcers in rats through mediating NF-κB and VEGF/PGE2 pathways.

The Ameliorative Impact of Centella asiatica on the Working Memory Deficit in Streptozotocin-induced Rat Model of Alzheimer Disease.

Introduction: Alzheimer disease (AD) is a complex neurodegenerative disorder with a progressive nature leading to neural damage and cognitive and memory deficit. The present study investigated the neuroprotective effects of Centella asiatica (CA) in Streptozotocin (STZ)-induced rat model of memory impairment and neuronal damage. Methods: The intracerebroventricular infusion of STZ (3 mg/rat) or saline (as the vehicle) was performed on days 1 and 3. CA (150 and 300 mg/kg/d) was administered through oral gavage for 21 days after model induction. We used the Y-maze test to assess the working memory-related performances of animals. Rats were then sacrificed, and their hippocampi were harvested for evaluation of neuronal density in the cornu ammonis (CA1, CA2, CA3) and Dentate Gyrus (DG) regions using stereology technique. Results: The intracerebroventricular infusion of STZ caused significant working memory impairment demonstrated in the Y-maze apparatus, with a significant decrease in alternative behavior compared to control animals (40.67±2.04 vs 73.00±1.88, P<0.0001). Oral administration of CA (150 and 300 mg/kg each day) for 21 days significantly improved STZ-induced working memory deficit (55.33±3.34 and 57.17±3.81 vs 40.67±2.04, P<0.013, P<0.004, respectively). Furthermore, 21 days of consecutive administration of CA significantly ameliorated STZ-induced neuronal loss in the CA1, CA2, and DG subfields of the hippocampus. Conclusion: Overall, these data demonstrate that CA increases neuronal density and improves cognitive impairment in the STZ-induced rat model of AD, thereby having promising therapeutic potential for neurodegenerative disorders. Accordingly, further studies are needed to determine the exact molecular mechanism of CA protective effects in brain disorders, particularly AD. Highlights: Centella asiatica (CA) improved the STZ-induced working memory deficit.CA could prevent hippocampal neural cell loss dose-dependent manner.CA improved memory through mitigating neuronal loss in hippocampus. Plain Language Summary: Memory loss is the first signs of dementia. It is well known that a healthy diet might be as good for your brain as it is for your heart. Numerous traditionally used medicinal herbs could significantly affect key events culminating in dementia and Alzheimer's disease. Centella asiatica, commonly known as Gotu Kola or Indian Pennywort, is a tropical, medicinal plant native to Southeast Asian countries. It is one of the becoming popular medicinal plants in the world. Centella asiatica (CA) is widely used in different traditional medicine systems for various purposes, such as reducing blood pressure, memory enhancement, and promoting longevity. In the present study, we tested the possible impact of CA leaf and stem extract in an animal model of memory damage. Memory impairment was induced in adult rats by intracerebral infusion of a neurotoxin chemical. Then, the memory-impaired animals were orally treated with 150-300 mg/kg of CA extract for 21 days. Finally, we tested their working memory by placing them in a Y-maze apparatus. Furthermore, their most involved brain part (hippocampus) was dissected, and its cell density was evaluated. Our findings exhibited that CA treatment considerably improved rats' memory performance, indicating by enhancing working memory score in the Y-maze task. In addition, CA treatment significantly prevented neuronal cell loss in the hippocampus of memory-impaired rats. This study shows that CA has beneficial effects on memory and cognitive function.

Evaluation of the in vivo and in vitro safety profile of Cuscuta epithymum ethanolic extract.

OBJECTIVE: Cuscuta epithymum (CE) is one of the most popular medicinal plants in the world. However, detailed information about its toxicity is not available. Hence, this study aimed to evaluate the safety profile of CE ethanolic extract in vitro and in vivo. MATERIALS AND METHODS: The extract's in vitro toxicity profile was investigated on normal fibroblast and cervical cancer cells by cytotoxicity test. In the next step, acute oral and intraperitoneal (i.p.) toxicity of the CE extract was evaluated in Wistar rats and BALB/c mice, respectively. Sub-acute oral toxicity was also examined by administering repeated oral doses of the CE extract (50, 200, and 500 mg/kg) to Wistar rats for 28 days. RESULTS: The CE extract exhibited a significant cytotoxicity on both normal (IC50 0.82 mg/ml, p<0.001) and cancer cells (IC50 1.42 mg/ml, p<0.001). Acute oral administration of a single dose of CE extract (175-5000 mg/kg) did not cause mortality; however, its i.p. administration caused mortality at doses greater than 75 mg/kg (i.p. LD50 154.8 mg/kg). In the sub-acute toxicity test, no significant effects in terms of weight change, organ weights, blood chemistry, or kidney pathology were observed. However, at 200 and 500 mg/kg doses, the CE extract significantly increased liver pathological scores compared to the control group (p<0.05 and p<0.01, respectively). CONCLUSION: CE exhibited toxicities in i.p. acute and repeated oral dose administrations. It showed identical cytotoxicity against normal and cancer cells. This herb must be prescribed cautiously by traditional medicine practitioners.

The effects of quercetin on seizure, inflammation parameters and oxidative stress in acute on chronic tramadol intoxication.

BACKGROUND: Tramadol is a widely used synthetic opioid for moderate to severe pain. Some studies have shown that tramadol can increase oxidative stress in different tissues of the body. Quercetin is also a substance with various biological effects, including antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, and cardioprotective activities. The current investigation aimed at determining the effects of quercetin, with or without naloxone, on tramadol intoxication. METHODS: This study was performed on 30 male Wistar rats divided into five groups: Group I) control group: intraperitoneal injections of normal saline 0.9% for 14 days; Group II) tramadol: 25 mg/kg for 14 days, and then a 50 mg/kg acute dose injection on the last day; Group III) acute quercetin (single dose): tramadol injection as with the second group plus 100 mg/kg of quercetin on the last day; Group IV) chronic quercetin: tramadol injection similar to the second group plus quercetin 100 mg/kg for 14 days; Group V) quercetin plus naloxone: tramadol injection similar to the second group plus injection of quercetin 100 mg/kg + intravenous naloxone 2 mg/kg on the last day, followed by a 4 mg/kg/h injection of naloxone for six hours. The rats were monitored for six hours on the last day, relating to the number and severity of seizures. Finally, the samples were prepared for biochemical investigation of the serum level of oxidative stress markers (MDA, SOD, NOx), inflammatory factors (IL-6, TNF-α), biochemical parameters (ALT, AST, creatinine, glucose) and hematological assay. The liver, heart, kidney, cortex, cerebellum, and adrenal tissues were collected to investigate the redox state. RESULTS: None of the treatments had positive effects on the number and severity of seizures. Chronic administration of quercetin led to alteration of some blood parameters, including reduced hemoglobin level and elevated platelet counts. Acute on chronic tramadol administration resulted in a significant rise in AST, where different treatments failed to reduce their levels down to the control group. CONCLUSION: chronic administration of quercetin showed decreased oxidative/nitrosative stress in the liver, kidney, adrenal, and heart tissues. Quercetin plus naloxone decreased oxidative stress in the heart and adrenal tissues, but adverse effects on the brain cortex and hepatic function. Single-dose quercetin reduced cardiac oxidative stress.

Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study).

BACKGROUND: Tramadol is a synthetic opioid and poisoning is increasing around the world day by day. Various treatments are applied for tramadol poisoning. Due to the unknown effects of tramadol poisoning and some of its treatments on blood glucose levels, this study was conducted to investigate the overdose of tramadol and its common treatments (naloxone, diazepam), and their combination on blood glucose levels in male rats. METHODS: This study was conducted in 45 male Wistar rats. The animals were randomly divided into five groups of 9. They received a 75 mg/kg dose of tramadol alone with naloxone, diazepam, and a combination of both of these two drugs. On the last day, animals' tail vein blood glucose levels (BGL) were measured using a glucometer at different times, including before the tramadol injection (baseline) and 1 hour, 3 hours, and 6 hours after wards. The rats were anesthetized and sacrificed 24 h after the last injection. Blood samples were then taken, and the serum obtained was used to verify the fasting glucose concentration. Data were analyzed using SPSS software at a significance level of 0.05 using a one-way analysis of variance (ANOVA) and a generalized estimating equation (GEE). RESULTS: According to the GEE model results, the diazepam-tramadol and naloxone-diazepam-tramadol groups showed blood glucose levels five units higher than the tramadol group (p < 0.05). The diazepam-tramadol group had significantly higher blood glucose levels than the naloxone-tramadol group (p < 0.05). The mean blood glucose levels before the intervention, 3 hours and 6 hours after the injection of tramadol did not differ between the groups, but the blood glucose levels 1 hour after the injection of tramadol in the group of naloxone-tramadol were significantly lower than in the control group (p < 0.05). Blood glucose levels did not differ between the groups 24 h after injection of tramadol. CONCLUSION: The results of the present study showed tramadol overdose does not affect blood glucose levels. The diazepam-tramadol combination and the diazepam-naloxone-tramadol combination caused an increase in blood glucose levels.

The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: an experimental study.

BACKGROUND: Tramadol is a widely used synthetic opioid. Substantial research has previously focused on the neurological effects of this drug, while the efficacy of various treatments to reduce the associated side effects has not been well studied. This study aimed to evaluate the protective effects of naloxone, diazepam, and quercetin on tramadol overdose-induced seizure and sedation level in male rats. METHODS: The project was performed with 72 male Wistar rats with an average weight of 200-250 g. The rats were randomly assigned to eight groups. Tramadol was administered intraperitoneally at an initial dose of 25 mg/kg/day. On the 14th day, tramadol was injected at 75 mg/kg, either alone or together with naloxone, diazepam, and quercetin (acute and chronic) individually or in combination. The rats were monitored for 6 h on the last day, and the number, the duration, and the severity of seizures (using the criteria of Racine) were measured over a 6-h observation period. The sedation level was also assessed based on a 4-point criterion, ranging from 0 to 3. Data were analyzed in SPSS software using Kruskal-Wallis, Chi-square, regression analysis, and generalized estimating equation (GEE) tests. The significance level was set at P < 0.05. RESULTS: The naloxone-diazepam combination reduced the number, severity, and cumulative duration of seizures compared to tramadol use alone and reduced the number of higher-intensity seizures (level 3, 4) to a greater extent than other treatments. Naloxone alone reduced the number and duration of seizures but increased the number of mild seizures (level 2). Diazepam decreased the severity and duration of seizures. However, it increased the number of mild seizures (level 2). In comparison with the tramadol alone group, the acute quercetin group exhibited higher numbers of mild (level 2) and moderate (level 3) seizures. Chronic quercetin administration significantly increased the number of mild seizures. In the GEE model, all groups had higher sedation levels than the saline only group (P < 0.001). None of the protocols had a significant effect on sedation levels compared to the tramadol group. CONCLUSION: The combined administration of naloxone and diazepam in acute-on-chronic tramadol poisoning can effectively reduce most seizure variables compared to tramadol use alone. However, none of the treatments improved sedation levels.

Intra-cerebroventricular Administration of Crocin Attenuates Sleep Deprivation-induced Hyperalgesia in Rats.

INTRODUCTION: Sleep deprivation can cause hyperalgesia and interfere with analgesic treatments. The aim of the present study was to establish an obligatory sleep-abstinence model and also evaluate the effects of Intracerebroventricular (ICV) injection of crocin on pain perception in Wistar rats. METHODS: In this experimental study, 35 adult male Wistar rats were randomly divided into 5 groups (n=7). The intra-ventricular cannulation was done for all rats before sleep deprivation. Sleep deprivation was performed by placing animals on a chamber equipped with an automatic animated conveyor (5 s with an interval of 3 min) for 72 h. Subsequently, the sleep-deprived animals received ICV injection of saline (MOD), Morphine 10 µg (MOR), Crocin 10 ug (Cr10), and Crocin40 µg (Cr40) using a microsyringe. Besides, a non-sleep-deprived group was allocated as a Control Group (NC) and only received an ICV injection of saline. Fifteen minutes after the ICV injections, pain perception was evaluated by the hot plate test (54±0.4°C). RESULTS: Compared with the NC group, latency significantly decreased in the MOD group (6.28±0.48 vs. 4.28± 0.48, P<0.0001). In comparison with the MOD group, both morphine (8.42±1.53) and crocin (7.60±1.45 for Cr10 and 8.14±0.89 for Cr40) could significantly increase latency in the sleep-deprived animals (P<0.0001). There was no statistically significant difference between the Cr10 and Cr40 (P=0.42), Cr10, and MOR (P=0.059) and Cr40 with MOR (P=0.86) groups. CONCLUSION: Our results indicated that crocin could attenuate hyperalgesia induced by sleep deprivation in rats.

Effects of bentonite nanoparticles inhalation on lung tissue and blood antioxidant indices in a rat model.

Bentonite is an inorganic clay material that is often easily dispersed as fine particles by air and water circulation, and most people are exposed to different concentrations of bentonite particles. Therefore, the inhaled effects of bentonite nanoparticles (BNPs) were studied in Wistar rats. Seventy-five rats were divided into five groups of 15: four exposure groups (0.1, 0.5, 2, and 10 mg/m3 of BNPs) and one control group. The rats were exposed for 30, 60, and 90 days to BNPs for 5 days a week (6 h/day) in whole-body inhalation chambers. Blood samples were collected to measure the levels of antioxidant activity of the contents such as total antioxidant capacity (TAC) and malondialdehyde (MDA). X-ray diffraction and scanning electron microscopy were used to identify nanoparticles. The results showed no significant difference in the effect of nanoparticles on levels of TAC and MDA in the studied groups based on the concentrations of nanoparticles. However, the level of MDA increased significantly with extending exposure time; there was a significant increase in the level of MDA content 90 days postexposure compared to 30 days postexposure at concentrations of 0.5, 2, and 10 mg/m3. Histopathological examination showed that inhalation exposure of rats to BNPs led to different histopathologic responses in the lung tissue, such as inflammatory infiltration, granulomatous inflammation, acute neutrophilic reaction in the early stages, and lung fibrosis. At the lowest concentration, BNPs have low or no toxicity, and inhalation of these nanoparticles at low concentrations does not affect the levels of MDA and TAC content. However, increased concentration and exposure time caused correspondingly greater increases in MDA and more damage to lung tissue.

Tramadol and the occurrence of seizures: a systematic review and meta-analysis.

Introduction: Tramadol is a synthetic opioid which is commonly used around the world to relieve moderate to severe pain. One of the serious possible complications of its use is seizures. The present study aims to investigate and summarize the studies related to tramadol and occurrences of seizures after tramadol use and factors influencing these seizures.Methodology: Our systematic review is compliant with PRISMA guidelines. Two researchers systematically searched PubMed/Medline, Web of Sciences, and Scopus. Cohort, case-control, cross-sectional studies, and clinical trials. The risk of bias was assessed using the Newcastle-Ottawa Scale After article quality assessment, a fixed or random model, as appropriate, was used to pool the results in a meta-analysis. Heterogeneity between the studies was assessed with using I-square and Q-test. Forest plots demonstrating the point and pooled estimates were drawn.Results: A total of 51 articles with total sample size of 101 770 patients were included. The results showed that seizure event rate in the subgroups of tramadol poisoning, therapeutic dosage of tramadol, and tramadol abusers was 38% (95% CI: 27-49%), 3% (95% CI: 2-3%), 37% (95% CI: 12-62%), respectively. Tramadol dose was significantly higher in the patients with seizures than those without (mean differences: 0.82, CI 95%: 0.17-1.46). The odds for occurrence of seizures were significantly associated with male gender (pooled OR: 2.24, CI 95%: 1.80-2.77). Naloxone administration was not associated to the occurrence of seizures (pooled OR: 0.47, 95% CI: 0.15-1.49).Conclusions: Our results demonstrate that the occurrence of seizures in patients exposed to tramadol are dose-dependent and related to male gender, but not related to naloxone administration. Given that, most of the evidence derives from studies utilizing a cross-sectional design, the association of tramadol with seizures should not be considered to be definitively established.

Improvement of glucose and lipid profile status with Aloe vera in pre-diabetic subjects: a randomized controlled-trial.

BACKGROUND: Pre-diabetes is a disturbing trend in the population, who are at risk of developing type-two diabetes. The aim of this study was to determine the effects use of Aloe vera in different doses on glucose and lipid profile in pre-diabetic subjects. METHODS: This study was a double blind randomized controlled trial (72 subjects) with pre-diabetes symptoms in 3 groups consumed capsules twice a day: Aloe vera 300 mg (AL300), 500 mg (AL500) and placebo (PL). Fasting blood glucose (FBS), HbA1C and lipid profile were evaluated in baseline, 4 or 8 weeks. On-way ANOVA, Friedman, Wilcoxon, Kruskal-Wallis , Mann-Whitney and Chi-square tests were used for within or between groups statistical analysis. RESULTS: FBS level in group AL300, showed significantly decreased in fourth week after the intervention, compared to PL in the same time (p = 0.001). Also, HbA1C level in this group at the eighth week after the intervention (p = 0.042), had a significant decrease. The levels of Total cholesterol and LDL-C, only in the group AL500 (p < 0.001 and p = 0.01), was significantly reduced, along with HDL-C level improvement just after eight weeks (p = 0.004). Triglyceride level showed a significant decrease (p < 0.045) just after four weeks use of AL500. CONCLUSIONS: The Use of Aloe vera extract in pre-diabetic patients, could revert impaired blood glucose within four weeks, but after eight weeks could alleviate their abnormal lipid profile.

Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain.

The research literature suggests that oxidative stress and pro-inflammatory factors influence neurotrophins in vitro. However, there is insufficient information about their effects on exercise training conditions, especially during high intensity trainings. This study aimed to compare the effects of 6weeks of high intensity interval and continuous training regimens on brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), hydrogen peroxide (H2O2), and tumor necrosis factor alpha (TNF-α) in the rat brain. For this purpose, twenty-four Albino Wistar rats were divided into sedentary control (SC), high intensity interval training (HIIT), and continuous training (CT) groups. Both HIIT and CT regimens increased H2O2 level and TNF-α concentration in the brain, and the alterations made were greater following HIIT than CT. In addition, both HIIT and CT regimens increased BDNF and GDNF concentrations significantly, with a higher elevation following HIIT than CT. Furthermore, H2O2 level and TNF-α concentration correlated positively with both BDNF and GDNF concentrations. Generally, high intensity interval training regimen, rather than continuous training regimen, is highly potential to improve BDNF and GDNF through a greater increase in H2O2 and TNF-α as oxidative stress and pro-inflammatory factors.

Cardiac effects of cupping: myocardial infarction, arrhythmias, heart rate and mean arterial blood pressure in the rat heart.

This study was carried out to determine the effects of cupping on hemodynamic parameters, arrhythmias and infarct size (IS) after myocardial ischemic reperfusion injury in male rats. Rats were randomly subjected to dry or wet cupping. While dry cupping simply involved stimulation of the skin by suction, in wet cupping, scarification of the back skin was also carried out with a surgical blade and 0.5 ml blood was sucked out in each session. For ischemic reperfusion injury, rats were subjected to 30 min of left anterior descending coronary artery occlusion and 120 min of reperfusion. Our results show that cupping did not change the baseline heart rate or mean arterial blood pressure. Ischemic reperfusion injury caused an IS of 50 ± 5%, whereas dry cupping, single and repeated wet cupping significantly reduced IS to 28 ± 3%, 35 ± 3% and 22 ± 2% of area at risk, respectively. The rate of ischemic induced arrhythmias was significantly modified by wet cupping (P < 0.05). These results indicate for the first time in rats that cupping might be cardioprotective in the ischemic reperfusion injury model.

Influence of ramiprilat and losartan on ischemia reperfusion injury in rat hearts.

UNLABELLED: HYPOTHESIS/INTRODUCTION: Our aim was to investigate whether a non-hypotensive dose of ramiprilat and losartan has myocardial protective effects during myocardial ischemia/reperfusion in vivo. MATERIALS AND METHODS: Three groups of rats were given 10 mg/kg per day of losartan for one (L-1W), four (L-4W) or 10 (L-10W) weeks. Another three groups were given 50 µg/kg per day of ramiprilat for one (R-1W), four (R-4W) or 10 (R-10W) weeks. The animals underwent 30 min of left anterior descending artery occlusion and subsequent reperfusion for 120 min. RESULTS: Myocardial infarct size (IS) was reduced in R-1W (28.4 ± 6.3%, p < 0.001), R-4W (27.8 ± 7.4, p < 0.001), L-4W (31.8 ± 6%, p < 0.05) and L-10W (25.3 ± 5.7, p < 0.001) groups compared with a saline group (48.3 ± 7.8%). A significant reduction in the number of ventricular ectopic beats (VEBs) was noted in groups R-1W (209 ± 41, p < 0.01), R-4W (176 ± 39, p < 0.01), L-4W (215 ± 52, p < 0.05) and L-10W (191 ± 61, p < 0.01 vs. saline 329 ± 48). The incidence of irreversible ventricular fibrillation (VF) and mortality were decreased significantly only in L-10W group. There were no significant decreases in episodes of VT, the incidence of irreversible VF and mortality in all of the groups treated with ramiprilat. CONCLUSION: These data indicate that losartan and ramiprilat protect the heart against ischemia/reperfusion injury independently of their hemodynamic effects but in a time-dependent manner.

Pretreatment with hyperoxia reduces in vivo infarct size and cell death by apoptosis with an early and delayed phase of protection.

OBJECTIVE: Exposure to normobaric hyperoxia protects the heart against ischemia-reperfusion injury ex vivo. In the present study, we investigated the effect of the early and late phase of hyperoxia on in vivo myocardial infarction and apoptosis. METHODS: Rats were exposed to room air preoxygenation (O(2)≥ 95%) followed by regional ischemia (30 min) and 0, 90, 180, and 360 min of reperfusion. Hyperoxic exposure was performed for 120 min either immediately or 24h before coronary occlusion followed by 360-min reperfusion. Infarct size was evaluated by Evans blue/triphenyltetrazolium chloride staining. Apoptosis in the infarcted area was evaluated by terminal deoxy-nucleotidyl transferase-mediated deoxy uridine triphosphate (dUTP) nick end-labeling (TUNEL). Caspase 3 activity was measured by fluorometric enzyme assay, Bcl-2 and Bax protein expression assessed by western blotting and DNA laddering assessed with DNA gel electrophoresis. RESULTS: The infarct size did not increase with increasing duration of reperfusion. However, apoptosis as evaluated by Bcl-2/Bax ratio, caspase 3 activity, and TUNEL-positive cells increased with increasing time of reperfusion. Both early and delayed pretreatment with hyperoxia reduced infarct size (p = 0.0013, p = 0.046), ameliorated ischemic arrhythmias and increased Bcl-2/Bax ratio (p = 0.015, p = 0.0159). Only hyperoxia immediately before coronary occlusion decreased caspase 3 activity (p = 0.026) and decreased TUNEL-positive staining (p = 0.046) with no visible DNA laddering. CONCLUSIONS: Detection of myocardial apoptosis increased with prolongation of reperfusion time, as opposed to infarct detection where reperfusion was essential to detect infarction, but the infarct size did not increase with time. Pretreatment with hyperoxia significantly decreased infarct size and apoptotic cell death. Pretreatment, immediately before coronary occlusion, was most cardioprotective.

Hyperoxia-induced protection against rat's renal ischemic damage: relation to oxygen exposure time.

BACKGROUND: Pre-exposure to hyperoxic gas (>or= 95%) has been shown to protect the heart and central nervous system from ischemia-reperfusion injury. In the present study, we investigated whether oxygen pretreatment induces delayed renal protection in rats. The possible role of some renal antioxidant agents was also investigated. MATERIALS AND METHODS: Adult male Wistar rats were kept in a hyperoxic (HO) (>or= 95% O(2)) environment for 0.5 h, 1 h, 2 h, 3 h, 6 h, and 2 h/day for three consecutive days and 4 h/day for six consecutive days, and control group (IR) animals were kept in the cage with no HO, one day before subjecting their kidney to 40 minutes of ischemia and 24h of reperfusion. Renal function was assessed by comparing plasma creatinine (Cr), blood urea nitrogen (BUN), creatinine clearance (CLCr), and fractional excretion of sodium (FENa%). Histopathological injury score was also determined according to the Jablonski method. To examine the antioxidant system induction by hyperoxia, we measured renal catalase and superoxide dismutase activity, and renal glutathione and malondialdehyde content. RESULTS: Our data demonstrated that only in 4 h/day HO for six consecutive days, the renal function tests (Cr, CLCr, BUN, and FENa%) and Jablonski histological injury were better than control group (p < 0.05). The beneficial effect of oxygen pretreatment in this group was associated with increased renal catalase activity compared with those obtained from control group (p < 0.05). CONCLUSION: The present study demonstrates that repeated exposure to hyperoxic (>or= 95% O(2)) environment can reduce subsequent rat's renal ischemia-reperfusion damage. Induction of endogenous antioxidant system may partially explain this beneficial effect of hyperoxic preconditioning.