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Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to determine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity.

Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis. Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05.Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE. Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.

Background: Individuals with diabetes mellitus are at serious risk of a wide range of cardiovascular complications. Urotensin 2 and its receptors play an important role in the development of cardiovascular diseeases through production of reactive oxygen species (ROS). Resveratrol is a polyphenol with antioxidant and anti-diabetic properties. The present study aimed to investigate the effects of resveratrol on urotensin 2 and its receptors in the heart tissues of diabetic rats. Materials and Methods: In this experimental study, 48 male Wistar rats were divided into six groups (N= 8 in each group). Resveratrol was prepared in 0.5% carboxymethyl cellulose and given to the rats through oral gavage. At the end of the 60 days of treatment with resveratrol, rats’ heart tissue was collected. Results: The weight of diabetic rats treated with 10 and 90 mg/kg bw of resveratrol significantly increased compared with the diabetic group. Furthermore, the serum levels of FBS, lipids, MDA, CK-MB and LDH decreased in the treated diabetic rats compared with the control group. Moreover, concentration of urotensin 2 and its receptors significantly decreased in the heart tissues of the diabetic rats treated with resveratrol at the dose of 10 mg/kg bw compared with the control group. Conclusion: The current study indicated that resveratrol decreased FBS, lipids, weight, MDA and cardiac enzymes. Furthermore, resveratrol significantly reduced urotensin 2 and its receptors, which indicates its moderating effect on diabetes complications.

Background: Aphanizomenon flos-aquae (AFA) is a type of blue-green algae and contains a source of biological compounds. These microalgae have many beneficial health effects. Recently, fucoidan, known sulfated polysaccharide component of AFA algae, has been claimed to stimulate stem-cell mobilization in animal models. Stem cells play an essential role in tissue repair process. In this study, we use excisional full thickness wound model to investigate the effectiveness of trademark AFA extract on skin wound repair process. Methods: In this experimental study, 21 adult male Wistar rats (weighing 200-250 g) were used and under general anesthesia (intraperitoneally with a ketamine/xylazine solution), two round excisional wounds were created under sterile conditions by a 6 mm punch on the dorsum (paravertebral area) of all rats. Animals were randomly assigned into 3 groups. In groups 1 and 2 (SE-200, SE-400), StemEnhance© (StemTech Health Sciences Inc. British Columbia, Canada) were given respectively 200 or 400 mg/kg by oral gavage once daily and in group 3 (Sham), distilled water (DW) was given to all subjects. Post-wounding gavage of StemEnhance or DW started from 1st day and continued to 7th day. The wound surface area was monitored daily by digital camera and assessed by Image Tool™ software, version 3.5 (UTHSCSA, San Antonio, TX, USA). At 9th day post-wounding animals were sacrificed and repaired tissues were harvested by and assessed by a 8 mm punch. Repaired skin areas were processed for hematoxylin and eosin (H&E). Histopathological parameters of healing including inflammatory cell infiltration, angiogenesis, and fibroblast count were assessed by pathologist. Our study was conducted in the Physiology Department of Medical School, Bushehr University of Medical Sciences, Iran, from October 2016 to March 2016. Results: Macroscopic imaging of wound area revealed that there was statistically significant difference in wound area reduction between SE-200 group and sham group on day 6 post wounding (P=0.032). Moreover, histological findings showed that the number of neutrophils, macrophages, fibroblasts, and microvessel density decreased in both StemEnhace-treated groups. There were no significant differences between two treatment groups. Conclusion: According to the obtained results it seems that the extract of Aphanizomenon flos-aquae algae positively affects wound healing process by ameliorating inflammatory response in early healing phases.

Background: Renal injuries associated with ischemia/reperfusion are a prevalent clinical phenomenon that can cause the emergence of progressive kidney diseases, eventually leading to chronic kidney injuries. The present study was conducted to evaluate the results obtained from non-invasive imaging using small-animal SPECT and investigate the recovery process in an animal model of renal ischemia/reperfusion. Materials and Methods: Male Wistar rats were used to establish a unilateral model of renal ischemia/ reperfusion injury. After occluding the left renal pedicle for 120 minutes, the animals were investigated in terms of reperfusion at 24 hours, one week and three weeks. At each time point, the intravascular injection of 99mTc-DMSA as well as scanning with the SPECT machine were conducted. Blood sampling and renal biopsy were also performed. Results: After 24 hours, the accumulated activity levels were significantly lower in the ischemic kidney compared to in the contralateral intact kidney. Severe renal histologic changes were also observed. After one and three weeks, the radiopharmaceutical uptake increased in the ischemic compared to both the contralateral kidney and the time point of 24 hours, and the absorbed activity was divided between the two kidneys in a more balanced fashion, which is quite consistent with the histologic results. Conclusion: The present findings suggest that non-invasive imaging with a small-animal SPECT system using 99mTc-DMSA provides researchers with an appropriate tool in rodent models of renal ischemic damage for evaluating the long-term follow-up of kidney recovery. The obtained results also appear to be thoroughly consistent with invasive histological studies.

Background: Bleomycin-induced lung fibrosis has been accepted as an animal model for fibrosis in rats. The aim of this study was to evaluate the effects of saffron aqueous extract on this disorder paving the way for more investigation in treating idiopathic pulmonary fibrosis in human. Methods: Male Wistar rats (250–300 gr) were instilled a single dose of bleomycin (5 mg/kg) via intratracheal tube (n=6) in 2015. Sham group received normal saline. Saffron aqueous extract (50 mg/kg and 100 mg/kg) were given orally in two different treated groups with bleomycin for 28 days. Lung Indices was calculated at the end of this experiment. Lung segments fixed in 10% formaldehyde were used for pathological preparation with Hematoxylin & Eosin and trichrome staining. Results: The body weight was decreased and lung Indices increased in bleomycin group (P

Background: Remote Ischemic Preconditioning (RIPC) improves exercise performance, and since this phenomenon has two phases, the aim of the current study was to investigate the delayed effects of remote ischemic preconditioning on cardiopulmonary function in athletes and non-athletes. Materials and Methods: 25 male and female students were studied in two main athletes and non-athletes groups. RIPC was induced by using 3 cycles of alternative 5 minutes ischemia and 5 minutes reperfusion at arms of participants. Cardiopulmonary tests were measured before, after and 24 hours after inducing remote ischemic preconditioning. Maximum oxygen consumption (VO2max) estimated by using queen steps test. Results: Analysis of data demonstrated that delayed RIPC in non-athletes group caused significant improvement in Forced Expiratory Volume in one second (FEV1) and Maximum Voluntary Ventilation (MVV) and noticeable improvement in some other parameters of pulmonary function tests. Moreover, it decreased systolic blood pressure and heart rate and decreased lactate release in both groups especially athletes group but it had no significant effect on VO2max of both groups. Conclusion: Delayed RIPC improves cardiovascular function of athletes and pulmonary function of non-athletes subjects. Thus, it can be considered as a good replacement for doping to improve sports performance of subjects in sports tournaments.

Background: We investigated the hemodynamic changes (Inotropic, chronotropic and arrhythmogenic) in intrave­nously envenomed anesthetized rats with Hemiscorpius lepturus venom. The neutralizing potencies of different drugs and commercial antivenom were assessed simultaneously. Methods: Different doses of the crude venom (100, 200 and 400μg/rat) were injected during five minutes via the femoral vein and cardiovascular changes were recorded in rats in Razi Institute Corporation, Karaj, Iran in 2017. The drugs (Atropine, lidocaine, propranolol and prazosin) were injected before the venom for determination of the coun­teracting effects. Different volumes (100, 500 and 1000µl) of the antivenom were pre envenomed to neutralize cardi­ovascular changes. Results: Temporary hypertension and bradycardia with no arrhythmogenic effects were depicted within twenty minutes. There was a difference in arterial pressure between the venom (400μg/rat) and the vehicle at 8 minutes (114.68±5.1mmHg versus 70.2±4.3mmHg). Elevation of the mean arterial pressure was inhibited by propranolol (2 mg/kg) and neutralized by prazosin (1mg/kg) while lidocaine (4mg/kg) and atropine (1mg/kg) had no effects. Pre­medication with Iranian commercial antivenom (1000μl) produced surprisingly temporary hypertension compared to the vehicle (140.84±4.5 versus 84.3±3.2). It had no neutralizing properties on blood pressure variation before the venom injection. Volume-expanded hypertension phenomenon was ruled out in a parallel study. Conclusion: This venom has vasoconstrictive effects in rats probably due to the presence of norepinephrine like ma­terials in its content or liberated from adrenal gland inhibited by prazosin premedication. The neutralizing effects of antivenom on venom-induced hypertension are questionable.

Tunicates are a large group of marine animals and have been named “tunicate” because of cellosic outer covering called a tunic. They are divided into four major classes of the ascidians, thaliaceans, appendicularians and Sorberacea. Ascidians are the most diverse tunicate group. They are a rich source of secondary metabolites. Alkaloids are the major class of this compounds that mostly, display biological activity. Pyridoacridine alkaloids have a significant biological activities and their main mechanism is DNA cleavage inhibition by reactive oxygen species (ROS). The pyrroloacridine alkaloids are mostly cytotoxic and also, indole alkaloids have numerous biological properties such as potent antiviral, anti-inflammatory and cytotoxicity activities. Pyrrole Alkaloids exhibited several biological properties, like strong calmodulin antagonistic, antileukemic, inhibiting Na+/K+ ATPase, activating the octomyosin ATPase, and inducing release of Ca2+ from sarcoplasmic reticulum. Tunicates are a rich source of peptides, cyclic oligopeptides and depsipeptides such as patellamides, Didemnin, Iodocionin, Apliamides, Halocidin, Dicynthaurin or Clavanin, with significant biological activities. Some compounds extracted from tunicates such as, Glabruquionones, prenylhydroquinone, geranylhydroquinone, Longithorone, scabellones, and conithiaquinones have different structures of linear or cyclic hydroquinone and quinones. They possess a wide range of biological activities as strong anti- tumor, anti-leukemia, anti-oxidant, anti-viral, and selective cytotoxicity properties. Other numerous compounds with unique structures and different biological activities such as Phallusiasterols with modulating the PXR receptor Lepadins with antiplasmodial and antitrypanosomal properties Coproverdine with cytotoxic and anti-tumor activity and Ningalin with a strong inhibitory effects on CK1δ, CDK5 and GSK3β kinase, have been extracted from these animals. A large diversity of biological active compoundes from marine tunicates explains this realty that they have a large capacity to search and devalopement new marine medicinal compounds. It is hoped that in the future, marine drugs, have a greater portion in the drugstore shelves.

Background: Considering the importance of the prevalence of diabetes which involves approximately 6% of the world's adult population, the need for low-calorie natural sweetener is felt more than ever. Recent studies have shown that hormones such as vaspin and Angiopoietin-like Protein3 (ANGPTL3) are associated with diabetes. The purpose of this study is to evaluate the effect of Stevia (Stevia rebaudiana ) plant (as a low calorie sugar) on serum concentration of vaspin and ANGPTL3 in diabetic rats. Materials and Methods: In this case-control study, forty male wistar rats weighing 180-250 g were divided into 5 equal groups: control, diabetic control and doses of 250, 500 and 750 mg/kg/BW/day of Stevia extract treatment. Diabetes was induced by intravenous injection of Streptozotocin (60 mg/kg). After 5 days, the rats with glucose above 300 mg/dl were considered as diabetic. The Stevia treatment groups received 250, 500 and 750 mg of Stevia extract for thirty days. At the end of experiment, blood samples were obtained measurement of vaspin, ANGPTL3, triglycerides, cholesterol, HDL, glucose, insulin and ALP. Histological study of the pancreas and liver biopsy were also performed. The results of the treatment and control groups were analyzed by SPSS software and P

Background: Previous studies have shown that use of supraphysiologocal doses of anabolic adrogenic steroids (AAS) associated with detrimental cardiovascular effects including ventricular hypertrophy, increased susceptibility to ischaemia/reperfusion injury, impairment of exercise-induced cardioprotection and sudden cardiac death. The aim of the present study was to evaluate the impact of 8 weeks treatment of AAS nandrolone decanoate (10 mg/kg/week), on ischemic preconditioning (IPC) phenomena in isolated hearts of sedentary rats. Materials and Methods: Three groups of animals were studied in the present study. Control ischemia/reperfusion injury group (IR), 2- Ischemic preconditioned group before main test ischemia and reperfusion (IPC+IR), and 3- Nandrolone treated ischemic preconditioned group before main test ischemia and reperfusion (Nan+IPC+IR). After two months of nandrolone and/or its solvent, the isolated Langendorff perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion. The IPC was induced by three cycles of 3-min occlusion and 3-min reperfusion of the left anterior descending coronary artery (LAD) before main test ischemia. Heart rate, left ventricular developed pressure (LVDP), rate pressure product (RPP), Max dp/dt, Min dp/dt and coronary flow were recorded during experiment. Infarction size was measured after 120 min reperfusion by TTC staining. Results: Eight weeks’ nandrolone treatment decreased body weight and increased cardiac to body weight ratio in treated rats. Nandrolone increased pre-ischemic base line cardiac function parameters in the rat hearts. Cardiac function recovery parameters in different time points during reperfusion were also greater in nandrolone treated rats compared to their respective controls. IPC decreased infarct size in the rats (P

Background: Anabolic-Androgenic Steroids (AAS) are mainly abused by athletes for improvement of muscle performance. Data suggest that the effect of AAS on neurobiochemicals related to behavioral response, may be underlies psychological adverse effects. Physical activity has beneficial psychophysiological effects, which may be related to increased serum levels of endogenous opioid peptides during exercise. In the present study we aimed to study the effect of chronic administration of nandrolone decanoate on beta-endorphin and met-enkephalin level in exercising rats. Methods: In this experimental study, forty male Wistar rats were randomly assigned in two main groups of sedentary and trained (2 weeks swimming exercise). Animals in each group were divided in two subgroups of control (received nandrolone solvent) and drug treatment (received nandrolone 15 mg/kg, 5 times/week). After two weeks of swimming exercise and drug treatment, serum levels of beta-endorphin and met-enkephalin were measured using ELIZA. Results: Our data showed that two weeks of swimming exercise training significantly increased serum beta-endorphin (114±5 vs. 98±5 ng/l in control group, P= 0.038) and met-enkephalin levels (1556±42 vs. 1475±27 ng/l in control group, P= 0.25). However, chronic administration of nandrolone decanoate in trained group considerably de-creased beta-endorphin (84±4 vs. 114±5 ng/l in control group, P= 0.002) and met-enkephalin levels (1378±36 vs. 1556±42 ng/l in control group, P= 0.011). The effect of supraphysiologic doses of nandrolone decanoate in control sedentary group was not statistically significant. Conclusion: In the present study we show that chronic nandrolone decanoate admin-istration attenuates effects of two weeks swimming exercise on serum opioid peptide and reduces the level of beta-endorphin and met-enkephalin. Keeping in mind that opi-oidergic system play an important role in behavior, athletes abusing anabolic steroid drugs may potentially experience changes in mood and behavior.

Introduction: Hyperoxia is an easy access preconditioner which attracts the researcher to use it in the clinic. Drug dependence is a widespread prevalence among different societies and one of the confounding factors in many diseases. Among different drugs, morphine dependence has shown preconditioning effects. According to both widespread phenomenon of drug addiction and use of hyperoxia in the clinic, there is a high probability of interaction between these two preconditioner factors on the ischemia-reperfusion injuries. Therefore, in this study, interaction of these two preconditioners on the ischemia-reperfusion injuries has been investigated. Method: Each containing ten rats, hearts were isolated in langendorff setup and after local ischemia, release of creatine phosphokinase (as a tissue damage index) and rate pressure product (as a mechanical function index) were measured. Furthermore, episode numbers of ventricular tachycardia and ventricular fibrillation (as arrhythmias indices) during ischemia and reperfusion period were studied separately. Results: normobaric hyperoxia in isolated morphine dependent rat hearts decreased creatine phosphokinase and increased mechanical function during reperfusion period. However, there was no significant difference in arrhythmias toward each of these preconditioners alone. Conclusion: preconditioning with normobaric hyperoxia in isolated morphine dependent rat heart induced reduction of tissue damage and improved cardiac function.

Background: Envenomation by Hemiscorpius lepturus is not painful and the clinical manifestations include bloody urine due to hemoglobinuria or hematuria, dermonecrotic reactions,cardiac arrhythmia and in minority of cases acute renal failure which may lead to death following disseminated intravascular coagulation in infants. Cardiac effects of envenomation by H. lepturus venom including inotropic, chronotropic and arrhythmogenic properties are not studied as now in rat hearts with Langendorff apparatus. Methods: Rat hearts were allowed to equilibrate in its buffer and cardiotropic plus arrhythmogenic effects induced by injection of different doses of H. lepturus venom were detected and recorded by computer acquisition based data in Langendorff apparatus. The neutralizing effects of Razi Institute antivenom and autonomic drugs were assayed in parallel studies. Results: Hemiscorpius lepturus venom (25 μg/100 l) treatment caused a negative inotropic (65.4 ± 3.2 versus 110.2 ± 3.4) and chronotropic effects (186.3 ± 4.2 versus 302 ± 6.3) in comparison to normal saline. Arrhythmogenic aspects including bradycardia, QRS widening and ST depression were induced by venom injection. Pre venom treatment (20 min) of Razi Institute antivenom (10 μl) neutralized cardiotropic effects but post venom injection (15 min later) had no therapeutic role. Pre (10 min before) and post (15 min after) injection of adrenaline (10 μl) neneutralized cardiotropic effects while pre venom injection (20 min) of propanolol (10 μl) had aggravating effects. Conclusion: Our study paves the way for further in vivo investigation of cardiovascular effects of this venom for finding suitable treatments instead of its ordinary antivenom medication in cardiogenic shock induced by the venom.