Pretreatment Of Rats Research Articles

Cardioprotective effect of hydroalcoholic extract of Brazilian red propolis against isoproterenol-induced myocardial infarction in rats

BackgroundThe pharmacological effects of propolis have mainly been investigated in various fields of medicine as an essential resource for the prevention and treatment of diseases. PurposeThis study examined the cardioprotective effect of hydroalcoholic extract of Brazilian red propolis (BRPHE) against isoproterenol (ISO)-induced myocardial infarction in rats. MethodsRats were pretreated with BRPHE (50, 75, and 150 mg/kg) for 30 days, with concurrent administration of ISO (85 mg/kg) during the last two days. The hemodynamic, biochemical, histological, and morphometric changes were monitored from control and experimental groups at the end of the experiment, i.e., on the 31st day. Phytochemical compounds were determinated by the UV–Vis spectrophotometric and UPLC-DAD-UV–Vis methods. ResultsISO-induced myocardial infarcted rats showed an increase in cardiac marker enzymes, i.e., in creatine kinase-NAC (CK-NAC) and CK-MB, tachycardia, myocardium necrosis, edema, hemorrhagic areas, infiltration of inflammatory cells like lymphocytes, and increased myocardial infarct size. However, pretreatment of ischemic rats with BRPHE significantly inhibited these effects of ISO. Thus, histopathological findings obtained for the myocardium further confirmed the biochemical findings. Flavonoids and phenols were identified in BRPHE. ConclusionOur results suggested that BRPHE pretreatment ameliorated myocardial injury in ISO-induced myocardial infarcted rats and exhibited cardioprotective activity.

NANONIZED CURCUMIN IMPROVED ORAL BIOAVAILABILITY OF BROMOCRIPTINE THROUGH CYP3A ENZYME INHIBITION IN RATS

Curcumin (CUR) a water insoluble dietary flavonoid and is reported to inhibit CYP3A4 enzyme. The objective of present study was to assess the effect of CUR and nanonized curcumin (NC) on bromocriptine (BRO) metabolism in rats. NC was prepared by antisolvent precipitation method and was evaluated for particle size and solubility. CYP3A inhibitory activity of CUR was assessed in vitro using erythromycin-N-demethylase (EMD) assay. CYP3A inhibitory effect of CUR and NC confirmed in vivo using pharmacokinetic study of midazolam. These findings were further confirmed by an in vivo pharmacokinetic study in which BRO was administered (10 mg/kg, p.o) to CUR and NC (60 mg/kg, p.o.) pretreated (10 days) rats and its plasma concentrations were determined by HPLC analysis. CUR significantly (p less than 0.05) inhibited CYP 3A activity in EMD assay. CUR and NC significantly (p less than 0.05) increased plasma concentrations of midazolam in dexamethasone pretreated rats. In addition, in vivo studies revealed that CUR and NC pretreatments significantly (p less than 0.05) increased Cmax and AUC and decreased CL/F of BRO compared with BRO group.NC pretreatment may increase the bioavailability of BRO which could be mediated through the inhibition of CYP 3A enzymes.

MTOR-mediated autophagy in the hippocampus is involved in perioperative neurocognitive disorders in diabetic rats.

IntroductionPerioperative neurocognitive disorders (PND) are common neurological complications after surgery. Diabetes mellitus (DM) has been reported to be an independent risk factor for PND, but little is known about its mechanism of action. Mammalian target of rapamycin (mTOR) signaling is crucial for neuronal growth, development, apoptosis, and autophagy, but the dysregulation of mTOR signaling leads to neurological disorders. The present study investigated whether rapamycin can attenuate PND by inhibiting mTOR and activating autophagy in diabetic rats.MethodsMale diabetic Sprague‐Dawley rats underwent tibial fracture surgery under isoflurane anesthesia to establish a PND model. Cognitive functions were examined using the Morris water maze test. The levels of phosphorylated mTOR (p‐mTOR), phosphorylated tau (p‐tau), autophagy‐related proteins (Beclin‐1, LC3), and apoptosis‐related proteins (Bax, Bcl‐2, cleaved caspase‐3) in the hippocampus were examined on postoperative days 3, 7, and 14 by Western blot. Hippocampal amyloid β (Aβ) levels were examined by immunohistochemistry.ResultsThe data showed that surgical trauma and/or DM impaired cognitive function, induced mTOR activation, and decreased Beclin‐1 levels and the LC3‐II/I ratio. The levels of Aβ and p‐tau and the hippocampal apoptotic responses were significantly higher in diabetic or surgery‐treated rats than in control rats and were further increased in diabetic rats subjected to surgery. Pretreatment of rats with rapamycin inhibited mTOR hyperactivation and restored autophagic function, effectively decreasing tau hyperphosphorylation, Aβ deposition, and apoptosis in the hippocampus. Furthermore, surgical trauma‐induced neurocognitive disorders were also reversed by pretreatment of diabetic rats with rapamycin.ConclusionThe results demonstrate that mTOR hyperactivation regulates autophagy, playing a critical role in the mechanism underlying PND, and reveal that the modulation of mTOR signaling could be a promising therapeutic strategy for PND in patients with diabetes.

Hepatoprotective Effects of Calotropis procera (Ait.) R. Br Root Bark Extracts against Diethylnitrosamine Induced Liver Injury in Rats

Background: Diethylnitrosamine (DEN) is a hepatotoxin whose metabolic activation by liver cytochromes P450 is responsible for the necrosis, mutagenicity and carcinogenicity of liver cells. The purpose of this study was to evaluate the protective effects of Calotropis procera roots bark against DEN induced hepatocellular damage in rats.
 Material and Methods: Hepatoprotective activity of the ethanolic extract of Calotropis procera root bark were evaluated by induction of liver injury with DEN in Wistar male rats distributed in six groups of six. Serum hepatic markers, alanine amino transferase (ALAT), aspartate amino transferase (ASAT), alkaline phosphatase (ALP), total protein and albumin were evaluated and the enzymes antioxidant activities, superoxide dismutase (SOD) and catalase, as well as the level of malonedialdehyde (MDA) were determined in the liver homogenate. Histological analysis was carried out on sections of rat livers. Phytoconstituents have also been studied. Results: Pretreatment of rats with the extract showed a significant decrease in ALAT, ASAT and ALP while there was an increase in total protein and albumin compared to rats treated only with DEN. It also showed a significant increase in SOD and catalase and a decrease in MDA levels suggesting the hepatoprotective effect of the extract. Observation of liver sections confirmed the results of the biochemical parameters which would attest that the extract is hepatoprotective. Phytoconstituents such as sterols, triterpenes and phenolic compounds have been demonstrated.
 Conclusion: Ethanolic extract of Calotropis procera roots bark has shown hepatoprotective effects that could be due to its content in sterols and triterpenic and phenolic compounds.

Neuroprotective effects of sonochemical- synthesized SiO2 nanoparticles in vivo models of ischemic/reperfusion injury in stroke

Cerebral ischemic injury is one of the debilitating diseases that showed inflammation plays an essential role in aggravating ischemic damage. After synthesizing silica nanoparticles (SiO 2 NPs) by sonochemical method, serum parameters in the presence of different concentrations of SiO 2 NPs are measured for toxicity assay. Rats were separated randomly into control, ischemia/reperfusion, and ischemia/reperfusion + SiO 2 NPs groups. Transient forebrain ischemia induced with bilateral occlusion of both common carotid arteries followed by 60minuts of reperfusion. SiO 2 NPs were administered (500 mg/kg/day p.o.) 21 days before ischemia/reperfusion time. Animals sacrificed and frontal cortex and hippocampal tissues used to determine malondialdehyde (MDA) level, nitric oxide (NO), glutathione (GSH) levels, an essential antioxidant, superoxide dismutase (SOD), alterations in the level of cytokines, TNFα, IL-1β, MCP-1, and phosphor Ik-кB. We also revealed the involvement of NF-κB downregulation by using western blotting. We reported on a histological investigation. The results showed that SiO 2 NPs with a diameter of around 50 nm in dose of 500 mg/kg didn't change the level of liver enzyme (including ALT, AST and ALP) and hematological parameters. 500 mg/kg SiO 2 NPs showed significant effects on remission of behavioral impairment. Ischemia/reperfusion oxidative injury in the rat hippocampus demonstrated a significant increase in MDA, TNFα, MCP-1, IL-1β, phosphor Ik-кB, NO levels, and a significant decrease in GSH contents and SOD activities in the hippocampal tissue compared to the control group. Pretreatment of ischemic rats with SiO 2 NPs decreased the elevated levels of MDA, TNFα, MCP-1, IL-1β, phosphor Ik-кB, and NO levels. A significant alteration observed in SOD activities and GSH content results between treated and untreated ischemia/reperfusion brains in rats. Decreased protein level of NF-κB also measured in SiO 2 NPs-treated animals. Untreated ischemia/reperfusion brains had significantly decreased in number of cells in CA1 hippocampus, nevertheless SiO 2 NPs increase the normal cell and decrease the neurodegeneration in hippocampus but it was not significant alteration. SiO 2 NPs reduced the damage caused by cerebral ischemia/reperfusion in rats and its molecular mechanism attributed to the downregulation of NF-κB signaling pathway.

Lycopene and Chrysin through Mitigation of Neuroinflammation and Oxidative Stress Exerted Antidepressant Effects in Clonidine-Induced Depression-like Behavior in Rats

Depression is a severely debilitating psychiatric disorder that influences more than 15% of the population worldwide. It has been demonstrated that it is associated with a high risk of developing other diseases such as cardiovascular diseases, diabetes, stroke, epilepsy, and cancer. The current study examines the possibility of chrysin and lycopene having an antidepressant effect in a rat model of depression induced by clonidine, as well as the mechanisms underlying this effect, including the role of neuroinflammation and oxidative stress. Rats were allotted into seven groups. The rats in group 1 served as a control. Group 2 received lycopene only. Group 3 was provided chrysin only. Group 4 was administered clonidine and served as the model. Group 5 was offered lycopene and clonidine. Group 6 was administered chrysin and clonidine. Group 7 was given FLX and clonidine and represented the standard. The experiment lasted two weeks, during which behavioral, biochemical, histopathological, and immunohistochemical measurements were performed. Lycopene and chrysin were used to correct the concentrations of noradrenaline and serotonin hippocampal tissue concentrations. These findings were also improved by immunohistochemical analysis of GFAP, VEGF, caspase3, and histopathological examinations, in which pretreatment of rats with lycopene and chrysin reversed all clonidine-induced alterations. The current research demonstrates that lycopene and chrysin have an auspicious antidepressant effect against clonidine that provoked behavioral hopelessness in rats. Manipulating oxidative stress, inflammation, and apoptosis may partially represent the corrective mechanism for the neuroprotective actions against the depressive effect of clonidine.

CARDIOPROTECTIVE EFFECT OF CYANIDIN-3-O-GLUCOSIDE IN ISCHEMIC HEART IS MEDIATED VIA INHIBITION OF AUTOPHAGY

Abstract It is elevated proves that the polyphenolic compounds of natural origin, such as anthocyanins, being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed anthocyanins, may control ischemia/reperfusion (I/R) injury although how much sheltering occurs is not obvious. In the present study, the role of cyanidin-3-O-glucoside pretreatment of cardiac ischemia and dysfunction was studied. Cyanidin-3-O-glucoside in 3 doses (5, 10, and 15 mg/kg body weight), was introduced in vivo 5 min before a 45 min closure of the left anterior descending artery, followed by a 120 min reperfusion in male Wistar rats. Blood samples and cardiac tissue specimens were obtained for studying the cardiac markers and the expression of lncRNA-CTC-448F2.4, miR1273a, and mRNA-DCN (Decorin), Specimens of left ventricles were obtained and prepared for histopathological criteria. Specimens of pretreated rats showed minimal cardiac edema, hemorrhage, cellular inflammatory infiltration, and fibrosis in cardiac tissue samples. Notably, this protective administration of cyanidin-3-O-glucoside also produced a dose-dependent downregulation in lncRNA- CTC-448F2.4 and mRNA-DCN (Decorin, an important gene involved in the regulation of autophagy) with elevation in miR-1273a expressions. Cyanidin-3-O-glucoside pretreatment leads to improvements in cardiac function tests, enzymes, and myocytes. In conclusion, Cyanidin-3-O-glucoside is promising for the protection of the heart from injury following ischemia-reperfusion in the rat examination.

Therapeutic effect of fenugreek (Trigonella foenum-graecum) seeds extract against arsenic induced toxicity in Charles Foster rats

The prime objective of the present study was to establish fenugreek (Trigonella foenum-graecum L.) seeds extract as an antidote against arsenic induced hepato-renal toxicity in rats. The male Charles Foster rats (weighing 160-180 g) were selected to make arsenic intoxicated model. The arsenic treated group of rats were orally treated with sodium arsenite at the dose of 8 mg/kg body weight/day for 90 days. Thereafter, the arsenic pretreated rats were further administered with fenugreek ethanolic seeds extract at the dose of 250 mg/kg body weight/day for 90 days. After the completion of the treatment, animals of all the groups were sacrificed for the biochemical and histopathological estimation. The arsenic treated rats showed significant (p < 0.0001) alterations at the various hepatic and renal biomarker parameters and at serum MDA levels in comparison to the control rats. Significant (p < 0.0001) arsenic accumulation was also observed in the blood, liver and kidney tissues of the arsenic treated rats. However, after the administration with fenugreek seeds extract, significant (p < 0.0001) restoration was observed in the liver and kidney biomarker parameters and at haematological variables. Fenugreek seeds extract administration also significantly (p < 0.0001) reduced the serum MDA levels and arsenic concentration levels in blood, liver and kidney tissues, along with considerable restorations at the cellular architecture of liver and kidney tissues. The study concluded that fenugreek seeds possessed potential hepato-renal ameliorative effect against sodium arsenite induced toxicity in rats, and can be used for its therapeutic value against arsenic poisoning.

Anti-Ulcerogenic and Cytoprotective Effects of Saharian (Sidr) Honey from Algeria.

This study aimed at investigating the gastro-protective effects of Algerian Sahara (Sidr) honey from Apis mellifera intermissa against HCl/Ethanol-induced gastric ulcers in rats. Total phenolic content, antioxidant activity and phenolic compounds were determined. Then, three groups of rats (control, HCl/ Ethanol-induced ulcer, and orally administered honey) were used for the determination of gastro-protective effect of Sidr honey. Total phenolic content, total flavonoid content, and DPPH activity of the honey sample were determined as 47.35±3.35 mg GAE/ 100 g, 2.13±0.17 mg QE/ 100 g, and 229.24±0.02 mg/mL, respectively. Oral pretreatment of rats with honey (1.2 g/Kg body weight orally at an interval of 2 days) protected gastric mucosa against HCl/Ethanol-induced damage by decreasing ulcer score, the volume and acidity of gastric juice and increasing pH. These results were confirmed by the histological assessment, which demonstrated a significant gastro-protective activity of Saharian (Sidr) honey against HCl/Ethanol-induced stomach ulcer. Plasma tumor necrosis factor-α, IL-6 and PGE2 were also measured. Sahara honey significantly decreased the plasma TNF-α, PGE2, and IL-6 concentrations.

The antioxidant and neuroprotective effects of the Psychotria camptopus Verd. Hook. (Rubiaceae) stem bark methanol extract contributes to its antiepileptogenic activity against pentylenetetrazol kindling in male Wistar rats.

A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5mg/kg) on every alternate day, 1h after each daily oral pretreatment of rats (8 ≤ n ≤ 10) with MEPC (40, 80 and 120mg/kg), vehicle or diazepam (3mg/kg) for 43days. The kindling development was monitored based on seizure episodes and severity. Rats' brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.

Evaluation of antioxidant and anti-ulcerogenic effects of Eremurus persicus (Jaub & Spach) Boiss leaf hydroalcoholic extract on ethanol-induced gastric ulcer in rats

This study aimed to investigate the antioxidant and protective effect of E. persicus leaf hydroalcoholic extract (EPE) in preventing gastric ulcers induced by ethanol in rats. Wistar rats weighing 180-220g were randomly divided into five groups. These groups included negative control (normal) group, positive control (ethanolic) group, comparative control (ranitidine recipient) group, group recipient the dose of 250mg/kg plant extract, and group recipient the dose of 500mg/kg plant extract. One hour after gavage of the drug and extract, the gastric ulcer was induced by feeding 1ml of 96% ethanol to each animal except the rats of the negative control group. After one hour, the rats were killed, and their stomachs were separated. Then, the gastric Ulcer index (UI), pH, oxidative stress parameters, and histopathological changes in the stomach of all groups were measured. Pre-treatment of ethanol-induced rats with the EPE reduced (P < 0.05) the ulcer index and gastric juice pH, compared to ethanolic group rats. Furthermore, pre-treatment with EPE at a dose-dependent manner, alleviated the gastric oxidative stress injury in rats through increase the activity of CAT, tissue NO· and GSH levels. EPE also was able to decrease the levels of ROS, MDA, PCO and serum NO·. According to the results, it can be concluded that pre-treatment with EPE prevents the formation of gastric ulcers caused by ethanol, which can be attributed to the antioxidant activity of plant polyphenols compounds.

Impact of sex differences on thrombin-induced hydrocephalus and white matter injury: the role of neutrophils

BackgroundThrombin has been implicated in playing a role in hydrocephalus development following intraventricular hemorrhage (IVH). However, the mechanisms underlying the sex differences to the detrimental effects of thrombin post-IVH remain elusive.MethodThree-month old male and female Sprague-Dawley rats underwent unilateral intracerebroventricular (ICV) injections of 3U or 5U thrombin, or saline, to examine differences in thrombin-induced hydrocephalus and white matter injury. Mortality, and lateral ventricle volume and white matter injury were measured on magnetic resonance imaging evaluation at 24 h post-injection. In addition, male rats were pretreated with 17-β estradiol (E2, 5 mg/kg) or vehicle at 24 and 2 h prior to ICV injection of 3U thrombin. All rats were euthanized at 24 h post-injection for histology and immunohistochemistry.ResultsICV injection of 5U thrombin caused 100 and 0% mortality in female and male rats, respectively. 3U of thrombin resulted in significant ventricular dilation and white matter damage at 24 h in both male and female rats, but both were worse in females (p < 0.05). Furthermore, neutrophil infiltration into choroid plexus and periventricular white matter was enhanced in female rats and may play a critical role in the sex difference in brain injury. Pre-treating male rats with E2, increased thrombin (3U)-induced hydrocephalus, periventricular white matter injury and neutrophil infiltration into the choroid plexus and white matter.ConclusionsICV thrombin injection induced more severe ventricular dilation and white matter damage in female rats compared to males. Estrogen appears to contribute to this difference which may involve greater neutrophil infiltration in females. Understanding sex differences in thrombin-induced brain injury may shed light on future interventions for hemorrhagic stroke.

Oxidative Stress and Neuronal Injury After Cannabis and Ketamine Administration

Cannabis sativa and ketamine are common substances of abuse causing psychotic events and neurodegeneration. In this study, the effect of pretreatment with Cannabis sativa extract on oxidative stress, inflammatory mediators and brain damage induced by ketamine was investigated. Rats were treated with subcutaneous injections of cannabis extract (10, 20, 30 or 40 mg/kg; expressed as Δ9-THC content) daily for three weeks and then in combination with ketamine (15 mg/kg, intraperitoneally) for another 5 days. Rats were tested for biochemical markers of oxidative stress including malondialdehyde (MDA) reduced glutathione (GSH), and nitric oxide (NO) concentrations in brain. Paraoxonase-1 (PON-1) activity, and levels of the proinflammatory cytokines, interleukin-1β (IL-1β), and tumour necrosis factor-α (TNF-α) in brain were also determined at the end of treatment period. Results indicated that compared with the saline control group, ketamine induced significant elevation in brain MDA and NO, which was accompanied by depletion of GSH and inhibition of PON-1 activity. Ketamine also significantly increased brain IL-1β and TNF-α and induced neuronal necrosis, apoptosis and vacuolation. Cannabis sativa (20-40 mg/kg) pretreated rats showed lower levels of oxidative stress and inflammation and doses of 30 or 40 mg/kg slightly reduced neuronal apoptosis and necrosis. These findings suggest that cannabis constituents do not enhance the neurotoxic effects of ketamine and might partly counteract the effects of ketamine-induced NMDA antagonism by reducing the release of free radicals and inflammatory mediators in brain

Anti-diabetic Activity of Partially Purified Santalin A from the Heartwood of Pterocarpus santalinus L.f. in Alloxan-induced Diabetic Wistar Rat

The ever-increasing use of plant-based pharmaceuticals as alternatives to conventional drugs for disease management demands identification, isolation, and characterization of novel compounds. Despite the potential of plant extracts to mitigate the morbidity of diseases, several active principles are preferred to avoid the interference of other compounds. The promising health benefits of the extracts and isolated compounds of Pterocarpus santalinus in the treatment of diabetes, cardiovascular disease, cancer, and infections have been described. However, such studies on the active principle, namely, santalins, are not reported. In this study, we standardized the isolation of a mixture of santalins A and B from the heartwood of P. santalinus by column chromatography followed by preparative TLC and HPLC. The partially purified santalins were characterized by LC-MS, HR-MS, and 1 H NMR analyses. The isolated combination of santalins displayed higher total antioxidant and DPPH free radical scavenging activity in vitro than the crude heartwood extracts. Administration of the mixture of santalins A and B did not exhibit any antihyperglycemic activity in the liver, kidney, and pancreas of alloxan-induced diabetic rats. However, pretreatment of rats with a mixture of santalins at a dose of 1.0 mg/kg body weight prevented alloxan-induced diabetes as indicated by the normal blood glucose levels. Hyperglycemia-associated lipid peroxidation was abrogated in santalin-pretreated rats that did not develop alloxan-induced diabetes. Furthermore, the alterations in catalase, glutathione peroxidase, and glutathione-S-transferase activities in the pancreas of santalinpretreated rats could be responsible for preventing damage to the pancreas and thus non-induction of diabetes following alloxan treatment. Therefore, for the first time, we report the simplified procedure for isolating a mixture of santalins, including their ability to prevent the induction of diabetes in Wistar rats. The outcome of our study has significant clinical importance to the fact that supplementation of santalins may potentially avoid or delay the onset of diabetes in high-risk individuals.

Thymoquinone dose-dependently attenuates myocardial injury induced by isoproterenol in rats via integrated modulations of oxidative stress, inflammation, apoptosis, autophagy, and fibrosis

As rats develop myocardial infarction (MI) like lesions when injected with large doses of isoproterenol (ISO), this investigation was designed to evaluate the dose-dependent effects of thymoquinone (TQ) on ISO-induced myocardial injury in rats. Adult male rats were divided into negative control, TQ20 (20mg/kg/day), TQ50 (50mg/kg/day), ISO positive control, TQ20 + ISO, and TQ50 + ISO groups. In these rats, biochemical, immunobiochemical, and histopathological studies were carried out to evaluate myocardial oxidative stress, inflammation, apoptosis, fibrosis, and autophagy, and the changes in serum cardiac biomarkers. The results showed that TQ pretreatment in ISO-administered rats produced a dose-dependent significant reduction of the myocardial infarct size, markedly reduced the ISO-induced elevation in serum cardiac markers and demonstrated several other important findings related to the cardioprotective efficacy of TQ. First, this study is the first reported research work showing that TQ treatment could increase the myocardial reduced glutathione baseline level, adding an indirect antioxidant effect to its known direct free radical scavenging effect. Second, pretreatment with TQ significantly reduced the markers of myocardial oxidative stress, inflammation, fibrosis, and apoptosis. Third, TQ acted as an autophagy enhancer ameliorating myocardial cell damage and dysfunction. Thus, the morphological and biochemical changes associated with ISO-induced myocardial injury were ameliorated with TQ pretreatment. The extent of this improvement was significantly greater in the TQ50 + ISO group than in the TQ20 + ISO group. The present study, for the first time, demonstrates these dose-dependent effects of TQ in experimentally induced myocardial injury. These findings raise the possibility that TQ may serve as a promising prophylactic cardioprotective therapy for patients who are at risk of developing myocardial injury and against the progression of existent myocardial injury as in cases of MI.

Anti-oedematous and antinociceptive activities assessment of stem bark aqueous extract of Ficus exasperata Vahl. (Moraceae) in rat and mice.

Background: Ficus exasperata Vahl. (Moraceae) is widely used in African traditional medicine for the treatment of various diseases. The present study is undertaken to assess the anti-oedematous and antinociceptive activities of the stem bark aqueous extract of Ficus exasperata in mice and rats. Methods: The anti-oedematous activity was investigated following carrageenan or histamine-induced rat paw oedema models. Antinociceptive activity was evaluated using acetic acid induced writhing test (1 %, 10 ml/kg), capsaicin-induced neurogenic pain (32 µg/mL, 30 µL) and formalin-induced test (1%, 20 µL). Extract was administrated orally at 37.5, 75 and 150 mg/kg. Results: Pre-treatment of rats with Ficus exasperata stem bark aqueous extract exhibited significant inhibition of paw oedema during all the phases of both carrageenan and histamine induced edema in rat. The maximum inhibition percentages were 94.75 % (3 h) and 30.64 % after one hour at the dose of 37.5 mg/kg, respectively, in carrageenan or histamine models. Antinociceptive activity showed that aqueous extract reduced significantly (p &lt; 0.001) the pain induced by acetic acid with an inhibition percentage of 70.8% (150 mg/kg). In the formalin-induced test, the extract also reduced significantly (p &lt; 0.001) licking time during neurogenic phase and inflammatory phase with inhibition percentages of 44.75% and 52.78% respectively at the dose of 75 and 150 mg/kg. In addition, aqueous extract of F. exasperata reduced significantly (p &lt; 0.001) neurogenic pain induced by capsaïcin by 71.28 % at the highest dose (150 mg/kg). Conclusion: This finding suggests that the stem bark aqueous extract of Ficus exasperata possess potent anti-oedematous and antinociceptive activities.

Sinapic acid reduces ischemia/reperfusion injury due to testicular torsion/detorsion in rats.

This study aimed to investigate the protective effect of sinapic acid (SA) on biochemical and histopathological changes in an experimental testicular torsion-detorsion rat model. Twenty-four rats were randomised into four groups: sham group, ischemia/reperfusion (IR) group subjected to testicular torsion for 2hr and then detorsion for 4hr, and two groups treated with SA1 and SA2 (10mg/kg and 20mg/kg, by single intraperitoneal injection, 30min before reperfusion). Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured by an autoanalyzer, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO) oxidative stress parameters by spectrophotometric methods, and tumour necrosis factor (TNF-α), interleukin-1 beta (IL-1β), and interleukin 6 (IL-6) parameters by the Elisa method. In addition, immunohistochemical and histopathological examinations were performed on testicular tissues. There was no significant difference between the groups in terms of serum testosterone, FSH and LH levels (p>.05). SA significantly reduced increased testicular damage, oxidative stress, inflammation, cell death and also restored decreased antioxidant enzyme activities (p<.05). Pre-treatment of rats with SA reduced testicular dysfunction and morphological changes IRI. SA's antioxidant, anti-inflammatory, and antiapoptotic properties were found to be protective against testicular IR.

Pretreatment of diabetic aged rats with combination of ginsenoside-Mc1 and silibinin protects liver from ischemia-reperfusion injury through an AMPK-dependent mechanism

Abstract Objectives This study evaluated the protective efficacy of combination treatment with ginsenoside-Mc1 and silibinin against hepatic ischemia-reperfusion (IR) injury in diabetic-aged rats, and further explored AMPK’s role in this protection. Methods A high-fat diet/streptozotocin was used to induce type-2 diabetes in aged rats (20–24 months). Diabetic-aged rats were pretreated with ginsenoside-Mc1 (10 mg/kg, IP) and silibinin (50 mg/kg, IP), alone or in combination, for 4 weeks before induction of hepatic IR injury. Results Induction of IR injury in diabetic-aged rats significantly elevated plasma levels of hepatic alanine and aspartate aminotransferases and negatively affected liver histology. Levels of 8-isoprostane, ROS production, Bax, and cleaved-caspase-3 expression were higher and manganese-superoxide dismutase (MnSOD), glutathione, and Bcl2 and p-AMPK were lower in IR-receiving group. In comparison to individual treatments, the combination of ginsenoside-Mc1 and silibinin powerfully restored IR-induced changes in liver enzymes and histopathological indices, oxidative markers, AMPK, and apoptotic protein expressions. Inhibition of AMPK using compound-C in H2O2-stimulated HepG2 cells significantly abolished the protective effects of combination treatment. Conclusions Combination of ginsenoside-Mc1 and silibinin was superior to their alone usage in protecting hepatocytes of diabetic-aged rats from oxidative/apoptotic damages following IR injury, through an AMPK-mediated mechanism.

Extracellular Vesicle TGF-β1 Is Linked to Cardiopulmonary Dysfunction in Human Immunodeficiency Virus.

Extracellular vesicles (EVs) have emerged as important mediators in cell-cell communication; however, their relevance in pulmonary hypertension (PH) secondary to human immunodeficiency virus (HIV) infection is yet to be explored. Considering that circulating monocytes are the source of the increased number of perivascular macrophages surrounding the remodeled vessels in PH, this study aimed to identify the role of circulating small EVs and EVs released by HIV-infected human monocyte-derived macrophages in the development of PH. We report significantly higher numbers of plasma-derived EVs carrying higher levels of TGF-β1 (transforming growth factor-β1) in HIV-positive individuals with PH compared with individuals without PH. Importantly, levels of these TGF-β1-loaded, plasma-derived EVs correlated with pulmonary arterial systolic pressures and CD4 counts but did not correlate with the Dl CO or viral load. Correspondingly, enhanced TGF-β1-dependent pulmonary endothelial injury and smooth muscle hyperplasia were observed. HIV-1 infection of monocyte-derived macrophages in the presence of cocaine resulted in an increased number of TGF-β1-high EVs, and intravenous injection of these EVs in rats led to increased right ventricle systolic pressure accompanied by myocardial injury and increased levels of serum ET-1 (endothelin-1), TNF-α, and cardiac troponin-I. Conversely, pretreatment of rats with TGF-β receptor 1 inhibitor prevented these EV-mediated changes. Findings define the ability of macrophage-derived small EVs to cause pulmonary vascular modeling and PH via modulation of TGF-β signaling and suggest clinical implications of circulating TGF-β-high EVs as a potential biomarker of HIV-associated PH.

The combination of intermittent electrical stimulation with acute intermittent hypoxia strengthens genioglossus muscle discharge in chronic intermittent hypoxia-pretreated rats

ObjectiveExploring whether the genioglossus discharge in chronic intermittent hypoxia(CIH) – pretreated rats could be enhanced by intermittent electrical stimulation combined with acute intermittent hypoxia(AIH). MethodsRats were pretreated with CIH for 4 weeks and then were randomly divided into 6 groups: time control, intermittent electric stimulation, AIH, intermittent electric stimulation + AIH, continuous electric stimulation and continuous hypoxia exposure. The genioglossus discharges were recorded and compared before and after stimulation. Normoxic-treated rats were grouped and treated with the same stimulation protocols. ResultsIntermittent electrical stimulation or AIH temporarily increased the activity of the genioglossus discharge, in which the degree of the increase was significantly higher in CIH-pretreated rats than in normoxic rats.After intermittent electrical stimulation, AIH evoked a sustained elevation of genioglossus discharge activities in CIH-pretreated rats, in which the degree of the increase was significantly higher than in rats induced by a single intermittent electric stimulation. ConclusionIntermittent electrical stimulation combined with AIH strengthens the genioglossus plasticity in CIH-pretreated rats.