Search

Immunosuppressive drugs used in the transplantation period are generally defined as induction and maintenance therapy. The use of immunosuppressants, which are particularly useful and have fewer side effects, decreased both mortality and morbidity. Many drugs such as steroids, calcineurin inhibitors (cyclosporine-A, tacrolimus), antimetabolites (mycophenolate mofetil, azathioprine), and mTOR inhibitors (sirolimus, everolimus) are used as immunosuppressive agents. Although immunosuppressant drugs cause many side effects such as hypertension, infection, and hyperlipidemia, they are the agents that should be used to prevent organ rejection. This shows the importance of individualized drug use. The optimal immunosuppressive therapy post-transplant is not established. Therefore, discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard.Our review discussed the mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation.

Valproate (VPA) induced changes in ovarian morphology are observed in humans with epilepsy and in non-epileptic animals. The effects of lamotrigine (LTG) on female reproduction is not well known. We investigated whether LTG might be a safer drug for use with patients of reproductive age. Forty Wistar albino female rats were divided into five groups. The control group was injected with saline-vehicle solution. The low dose (LD)-VPA group was injected with 100 mg/kg VPA. The high dose (HD)-VPA group was injected with 500 mg/kg VPA. The LD-LTG group was injected with 10 mg/kg LTG. The HD-LTG group was injected with 50 mg/kg LTG. We evaluated histological and biochemical changes in the ovaries. The number of atretic and cystic follicles was increased in the HD-VPA and HD-LTG groups compared to the control group. A significant increase in malondialdehyde level was found in the VPA groups compared to the control and LTG groups. No significant differences in total glutathione levels or superoxide dismutase activity were found among study groups. Catalase activity was significantly higher in HD-VPA and HD-LTG groups compared to the control, LD-VPA and LD-LTG groups. Prevalence and intensity of caspase-3 immunoreactivity in the luteal cells were significantly greater in the HD-LTG group compared to the control group. VPA administration caused polycystic ovarian syndrome-like changes in the ovary. We found that LD-LTG, which reflects the dose for humans, might be a safer option for use during the reproductive age.

Objective: The aim of this study was to evaluate histopathological, functional and bone densitometry examinations of the beneficial effects of dexpanthenol (DEX) on nerve regeneration in a rat mode...

Depression is a serious psychological disorder that affects a significant population. We investigated the antidepressant activities of four pyridazinone derivatives that contain the hydrazide moiety using the forced swimming test (FST). The compounds tested exhibited good antidepressant activity compared to duloxetine. The most promising compound was compound 2, which reduced the duration of immobility during FST. The toxic effects of the four compounds on the histomorphology of the liver and stomach tissue also was evaluated.

Panax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.

Background and Aims. Sepsis causes release of free oxygen radicals that destroy membrane integrity.We evaluated the antioxidant effects of parsley, Petroselinum crispum(Pc), which has been used therapeutically for centuries in Anatolia, using a rat model of sepsis caused by cecal ligation and puncture (CLP).Methods.Wistar albino rats were separated into four groups of eight: a sham group with incised and sutured abdomen, a Pc extract(PcE) group was given 2 g/kg parsley extract for 14 days by gastric gavage, a CLP group with sepsis caused by CLP and a PcE + CLP group given parsley extract for 14 days, then made septic by CLP. PcE is given for 14 days and then sepsis is performed by the CLP procedure. Results. The groups were compared in terms of hemogram, biochemical and histological characteristics. It has been proven that the administration of PcE before CLP-induced sepsis increases neutrophil, PLT counts and TAS levels which decrease with sepsis and decreases biochemical changes (BUN, AST, ALT, LDH, TOS, OSI) which increase with sepsis, to have a protective effect on sepsis . In the PcE + CLP group, the severity of intestinal infiltration was decreased significantly compared to the CLP group; epithelial damage was similar to the CLP group. In the PcE + CLP group, the crypt and villus length was greater and the decrease in Paneth cell degranulation intensity was found to be more than for the CLP group ; also, the morphology of the cells was similar to the Sham group. Discussion. PcE exhibit potential for prophylaxis for sepsis.

Objectives High anxiety levels may lead to mental and physical changes that may affect quality of life. Melatonin has anxiolytic properties. It has been reported that administration of melatonin reduces anxiety. In this study, we examined the preoperative and postoperative anxiety levels of living liver donors and the correlation between anxiety levels and endogenous melatonin levels. Materials and methods This prospective clinical study included 56 living liver donors who underwent right hepatectomy (39 women, 17 men; average age of 29 ± 7 years). The anxiety levels were evaluated by using the Spielberger State-Trait Anxiety Inventory Test with a form for this test used to measure the current state of anxiety score and another form used to measure the underlying anxiety score of the patient. These forms were applied preoperatively and postoperatively. Blood samples were taken simultaneously for melatonin levels. Melatonin levels were measured using high-pressure liquid chromatography. Our primary outcomes were to determine the preoperative and postoperative endogenous melatonin and anxiety levels of living liver donors and to investigate their correlations. Results A statistically significant difference was observed between preoperative and postoperative state of anxiety scores. The preoperative and postoperative underlying anxiety scores were similar. A statistically significant difference was found between the preoperative endogenous melatonin level and postoperative endogenous melatonin level. A significant correlation was not observed between the preoperative and postoperative current and underlying anxiety levels or endogenous melatonin levels. Conclusions Living liver donors had high anxiety levels during the preoperative and postoperative periods. A significant decrease was identified in the postoperative hour 24 endogenous melatonin level. These results may lay the foundation for interventions that can identify emotional changes as well as control and improve the mental health of living liver donors.

Amikacin (AK) is frequently used in the treatment of gram-negative and some gram-positive infections. However, its use is limited due to nephrotoxicity due to the increase in reactive oxygen radicals. The aim of this study was to investigate the role of carvacrol (CAR) against AK-induced nephrotoxicity in rats. Thirty-two Sprague Dawley rats were randomly divided into four groups as control (Vehicle), AK (400 mg/kg), CAR + AK (80 mg/kg CAR + 400 mg/kg AK), and AK + CAR (400 mg/kg AK + 80 mg/kg CAR) groups. AK and CAR were administered via intramuscular and per-oral for 7 days, respectively. Blood and kidney tissue samples were taken at the end of the experiment. Renal function and histopathological changes were compared, and the relevant parameters of oxidative stress and inflammation were detected. Histopathological findings (necrotic changes and dilatation and inflammatory cell infiltration) significantly increased in the AK group compared to the control group. Also, the rats in the AK group lost weight significantly. It was found that CAR treatment before and after AK significantly improved nephrotoxicity histopathologically (p

OBJECTIVE Sickle cell anaemia (SCA), an inherited chronic hematological disease affecting hundreds of thousand people worldwide, causes significant morbidity and reduced life expectancy about two or three decades. This study aimed to conduct a meta-analysis of the efficacy of voxelotor, 900 mg in patients with SCA. METHODS The research protocol was registered at the International Register of Prospective Systematic Reviews (PROSPERO), under the registration number: CRD42020147796. ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Conference Abstracts, Google Scholar, Ovid Medline, Scopus, Web of Science, and Wiley Online Library from 2015 through July 25, 2019, and bibliographies of review articles and eligible studies. Eleven eligible studies that evaluated the effectiveness of voxelotor, 900 mg in SCA. Based on pre-specified inclusion and exclusion criteria, 2 randomized, placebo-controlled studies were included in the meta-analysis. RESULTS The primary outcome measured was hemoglobin elevation, assessed in a highly similar fashion in both trials. There was a significant difference between voxelotor and placebo in haemoglobin change from baseline (mean difference [MD]: 0.87, 95% confidence interval [CI]: 0.67-1.06). Voxelotor also reduced markers of haemolysis, MD: -36.79, 95% CI: (-75.05) to 1.48 for unconjugated bilirubin that changes from baseline; MD: -19.09, 95% CI: (-44.06) to 5.88 for the percentage of reticulocytes that change from baseline and MD: -23.29, 95% CI: (-65.14) to 18.55 for LDH that change from baseline) but the difference was not statistically significant. CONCLUSIONS As a conclusion, voxelotor, 900 mg use significantly increased hemoglobin levels which of 1 g/dL elevation predicts a reduced risk of stroke (41%), albuminuria (53%), pulmonary arterial hypertension (57%), and mortality (64%) in recent studies. Voxelotor also reduced markers of hemolysis but failed to reach statistically significance in current evidence. Multicenter, randomized, placebo-controlled studies are on the way and will provide more evidence to see the potential of disease-modifying effects of voxelotor.

Coronavirus disease 2019 (COVID‐19) is a life‐threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID‐19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response as well as oxidative injury play a critical role in the pathogenesis of COVID‐19. In this review, we aimed to update knowledge about pathogenesis, clinical features and pharmacological treatment of COVID‐19 and review the potential beneficial effects of ancient antioxidant, anti‐inflammatory and immunomodulatory molecule melatonin for prevention and treatment of COVID‐19.

COVID-19 caused by SARS-COV-2 first appeared in the Wuhan City of China and began to spread rapidly among people. Rapid progression of the outbreak has led to a major global public health problem of a potentially fatal disease. On January 30, 2020, WHO declared the pandemic as the sixth public health emergency of the world. Upon this, the whole country has started to take the necessary precautions. The new coronavirus uses membrane-bound angiotensin-converting enzyme 2 (ACE2) to enter into the cells, such as SARS-CoV, and mostly affects the respiratory tract. Symptoms of COVID-19 patients include fever (93%), fatigue (70%), cough (70%), anorexia (40%) and dyspnoea (34.5%). The elderly and people with underlying chronic diseases are more susceptible to infection and higher mortality. Currently, a large number of drugs and vaccines studies are ongoing. In this review, we discussed the virology, epidemiological data, the replication of the virus, and its relationship with cardiovascular diseases on COVID-19 pandemics, treatment and vaccines. Thereby, this study aims to neatly present scientific data in light of many regarding literature that can be a clue for readers who research this disease prevention and treatment. SIGNIFICANCE OF THE STUDY: This review summarized current information on COVID-19 (epidemiology, pathophysiology, clinical, laboratory, cardiovascular diseases, ACE2 and pharmacological agents) for researchers and reveals guiding data for researchers, especially in the field of cardiovascular system, pharmacology, dysregulation of cellular function in disease, molecular and cell biology and physiology in the regulation of tissue function in health and disease.

Cardiovascular diseases are known to be the most fatal diseases worldwide. Ischaemia/reperfusion (I/R) injury is at the centre of the pathology of the most common cardiovascular diseases. According to the World Health Organization estimates, ischaemic heart disease is the leading global cause of death, causing more than 9 million deaths in 2016. After cardiovascular events, thrombolysis, percutaneous transluminal coronary angioplasty or coronary bypass surgery are applied as treatment. However, after restoring coronary blood flow, myocardial I/R injury may occur. It is known that this damage occurs due to many pathophysiological mechanisms, especially increasing reactive oxygen types. Besides causing cardiomyocyte death through multiple mechanisms, it may be an important reason for affecting other cell types such as platelets, fibroblasts, endothelial and smooth muscle cells and immune cells. Also, polymorphonuclear leukocytes are associated with myocardial I/R damage during reperfusion. This damage may be insufficient in patients with co-morbidity, as it is demonstrated that it can be prevented by various endogenous antioxidant systems. In this context, the resulting data suggest that optimal cardioprotection may require a combination of additional or synergistic multi-target treatments. In this review, we discussed the pathophysiology, experimental models, biomarkers, treatment and its relationship with genetics in myocardial I/R injury. SIGNIFICANCE OF THE STUDY: This review summarized current information on myocardial ischaemia/reperfusion injury (pathophysiology, experimental models, biomarkers, genetics and pharmacological therapy) for researchers and reveals guiding data for researchers, especially in the field of cardiovascular system and pharmacology.

Emine Turkmen Samdanci,1 Mustafa Huz,1 Onural Ozhan,2 Kevser Tanbek,3 Esra Pamukcu,4 Ayse Nur Akatli,1 Hakan Parlakpinar21Department of Pathology, Inonu University School of Medicine, Malatya, Turkey; 2Department of Pharmacology, Inonu University School of Medicine, Malatya, Turkey; 3Department of Physiology, Inonu University School of Medicine, Malatya, Turkey; 4Department of Statistics, Firat University Faculty of Science, Elaziğ, TurkeyIntroduction and aim: Methotrexate (Mtx) is an antineoplastic and immunosuppressive drug that may cause hepatotoxicity, whereas molsidomine (Mol) is a vasodilating and antioxidant agent. This study aimed to investigate the potential protective effects of Mol in Mtx-induced liver toxicity in rats.Materials and methods: Forty Wistar albino rats were equally divided into five groups: control, Mol, Mtx, Mol–Mtx, and Mtx–Mol. Following treatment, the animals were sacrificed, and liver tissue samples were histopathologically evaluated using Roening grading and Bcl-2 antibody staining. Tissue oxidants, antioxidants, and serum transaminases were measured and statistically compared across all groups.Results: No hepatic fibrosis or steatosis was observed in any of the groups. In the Mtx group, grade 2 liver injury and score 2 Bcl-2 antibody staining were observed; however, in the Mol–Mtx group, these were lower (grade 1, score 1). There were no statistically significant differences in serum transaminase levels among groups. Malondialdehyde levels were higher in all rats that received Mtx, but no differences in myeloperoxidase levels were observed among the groups. Levels of tissue antioxidants, including superoxide dismutase, glutathione (GSH) peroxidase (GSH-Px), and reduced GSH, were significantly higher in the Mol-treated and Mol pre-treated groups. Catalase (CAT) levels were elevated in all Mol-treated groups, but only in that group were CAT levels statistically significantly higher than in the control group.Conclusion: Our results suggest that some oxidant levels could increase following Mtx administration in the liver, possibly contributing to liver damage, whereas Mol could mitigate the histopathological and biochemical effects of hepatotoxicity. However, molecular studies are required to understand the exact mechanisms of these alterations.Keywords: methotrexate, molsidomine, hepatotoxicity, hepatic fibrosis

We aimed to investigate the protective and therapeutic effects of dexpanthenol (DXP) on liver injuries induced by ischemia-reperfusion (IR) in an in vivo rat model.Thirty-two rats were randomly divided into 4 experimental groups (n = 8 in each group: Sham, IR, DXP, and DXP+IR. DXP (500 mg/kg) was intraperitoneally administered for 30 min before 60 min of ischemia, followed by 60 min of reperfusion to rats in the DXP and DXP+IR groups. All rats were euthanized on day 10 to evaluate immunohistopathological changes as well as tissue levels of oxidants and antioxidants.IR decreased total glutathione (tGSH) levels in IR group when compared to the Sham group. DXP supplementation to IR group significantly ameliorated tGSH levels (P .05). IR also elevated myeloperoxidase production compared to the Sham group, whereas DXP treatment prevented these hazardous effects. However, plasma superoxidedismutase, catalase, and malondialdehyde levels did not differ between the DXP+IR than the IR rats. Histologic tissue damage was reduced in the DXP and DXP+IR group.Liver IR is an inevitable problem during liver surgery. Our results suggested that DXP pretreatment suppressed oxidative stress and increased antioxidant levels in a rat model of liver IR.

We evaluated the effects of melatonin on acetylsalicylic acid (ASA) induced gastroduodenal and jejunal mucosal injury. We used 40 postpubertal rats divided randomly into five groups of eight animals. The control group consisted of untreated animals. The Mel group was injected intraperitoneally (i.p.) with 5 mg/kg melatonin. The ASA group was injected i.p. with 200 mg/kg ASA. The ASA + Mel group was injected i.p. with 5 mg/kg melatonin 45 min after administering 200 mg/kg ASA i.p. The Mel + ASA group was injected i.p. with 5 mg/kg melatonin 45 min before administering 200 mg/kg ASA i.p. We found no statistically significant differences in mean histopathological scores in the ASA + Mel group compared to the ASA group. ASA caused shortened villi and loss of the apical villus in the duodenum. The histopathological score was increased and villus height was decreased in the ASA group compared to untreated controls. Treatment with melatonin attenuated the histological damage. In the ASA group, occasional areas showed erosion of villi in the jejunum; however, differences in mean histopathological score in ASA group compared to the other groups were not statistically significant. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities were measured in stomach, duodenal and jejunum tissue. We found increased MDA activity in both stomach and duodenal tissues in the ASA group compared to the control group (p < 0.05). We found no statistically significant changes in MDA levels in jejunal tissue in the ASA group compared to the control group. We found no change in SOD activity in either stomach or duodenal tissues in the ASA group compared to the control group. We observed decreased SOD activity in jejunal tissue in the ASA group compared to the control group (p < 0.05). We detected no change in GSH activity in stomach, duodenal or jejunal tissues in the ASA group compared to the control group. The stomach damage was less in melatonin treated groups, but the lesions were not completely eliminated. The jejunum in the ASA group retained a nearly normal appearance. We found that melatonin exhibited some healing effects on ASA induced duodenal mucosal injury.

Scope: We investigated the potential beneficial effect of Apocynin (APO) on motor and cognitive functions in experimental Alzheimer’s disease (AD). Materials and Methods: Experimental AD was induced in rats by intraventricular streptozotocin (STZ) injection. Sham group received artificial cerebrospinal fluid (CSF). Both groups were randomly divided into two subgroups. One of the subgroups received intraperitoneal APO for while the other had normal saline (NS). The animals were evaluated with rotarod, accelerod and Water-Maze tests before and after the treatment. Additionally, biochemical markers of oxidative stress such as malondialdehyde (MDA) and reduced glutathione (GSH) were analyzed from brain specimens. Standard histological evaluation and transmission electron microscopy (TEM) were used to evaluate the neural damage. Results: The difference between STZ+NS in comparison with CSF+NS, CSF+APO and STZ+APO were statistically significant on 30 and 40 rpm on rotarod test. GSH levels, accelerod and Water-Maze test results were not statistically significant between subgroups. However, MDA differences between STZ+NS in comparison with CSF+NS, CSF+APO and STZ+APO were statistically significant. Hemotoxilene eozine staining and TEM results showed apocynins protective effect. Conclusion: These results indicate that APO can provide neuro-protective effect for motor but not for cognitive performance in experimental AD. Keywords: Alzheimer’s disease, Streptozotocin, Apocynin, Rotarod test, Accelerod test, Water-Maze test

Purpose: To investigate the cause of congenital anomalies resulted from gestational diabetes on fetal cardiac tissue in experimental animal study model. Methods: Totally 12 female Wistar albino rats were divided into two groups, each consisting of 6 rats. Streptozotocin (60 mg/kg) was administered intraperitoneally to the study group by dissolving in citrate solution. The rats with a blood glucose level of 200 mg/dL and above were considered to be diabetic rats. Total antioxidant status (TAS), total oxidative stress (TOS) and oxidative stress index (OSI) values were calculated in the cardiac tissues and maternal serum samples of the fetuses delivered by cesarean section after the mating process. The cardiac tissues were also subjected to histopathological examination. Results: TOS and OSI values in fetal cardiac tissues of the diabetic rats were found to be significantly higher than that of the control group (p=0.026 and p=0.005). Histopathological examination revealed that the mitotic index was lower and the cell organization was found to be damaged in the fetuses of the study group rats. Conclusion: Increased levels of free oxygen radicals considered to be due to hyperglycemia may cause congenital anomalies, especially during organogenesis period, by disrupting cell homeostasis and adversely affecting mitosis.

As aim of this study, the knowledge of whether vinpocetine (VINPO) is cardioprotective or not following isoprotenol (ISO) induced cardiac ischemia in rats. In myocard infarction, the one of the responsible mechanisms of injury is oxidative damage and inflammmation. The effect of Vinpo which is the potent antioxidant and anti inflammatory agent aimed to reveal as the biochemical, electrophysiological, and histopathologic parameters. In this study, thirty- two Wistar-Albino male rats (in the estimated weight of 250-400gm.) were divided into four groups, each consisting of eight rats. The group 1 named as sham, no any drug used in this group. Group 2 named as iso group, only isoprotenol was adminestered, the group 3 named as vinpo and iso group, here initially vinpocetine then isopretenol were used, and the group 4 named as iso and vinpo, here initially isoprotenol then vinpocetine were used. For the rats in group 2, in first and second day isoprotenol adminestered at a dose of 120mg/kg using an intraperitoneal injection. At third and fourth day no any drug used. And at fifth day the experiment terminated. For the rats in group 3, at the first and second day Vinponcetine adminestered at adose of 20 mg/kg using an intraperitoneal injection, after 30 minute isoprotenol administered at adose of 120mg/kg using an intraperitoneal injection. At third and fourth day no any drug was used. And at fifth day experiment was terminated. Lastly for the rats in group4, first and second day isoprotenol administered at adose of 120mg/kg using an intraperitoneal injection, at third and fourth day vinpocetine adminestered at adose of 20 mg/kg using an intraperitoneal injection, and at fifth day experiment terminated. Prior to termination of experiment the pulse rate and ECG changes were recorded. After completion of experiment protocols blood samples and cardiac tissue samples were recieved. For the knowledge of effects of vinpocetine experimental miyocardial ischemia induced in rats, and the serum myoglobulin, total creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanin aminotransferase (ALT), measured. In myocardial tissue as an antioxidative system and an oxidative stres markers; malonylaldehate (MDA), Superoxidedismutase (SOD), Catalase (CAT), Glutathionperoxidase (GPx), GSH, Total oxidant status (TOS),Total antioxidant status(TAS),Oxidative stres index (OSI) studied. As a result, Vinpocetin showed positive impact on cardiac functions. With all of these for the best clear results, advanced studies are needed. [Med-Science 2017; 6(4.000): 629-634]

Myocardial ischemia/reperfusion injury is one of the main causes of morbidity and mortality in the world. This injury is experienced by patients suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. Ischemia can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue, termed reperfusion, can result in further damage. The serum markers of myocardial injury are used to help in establishing the diagnosis of myocardial infarction. Use of various biochemical markers, including lactate dehydrogenase (LDH), creatine kinase (CK) total enzyme activity, CK-MB activity, Myoglobin, CK-MB mass, cardiac troponin I (cTnI), and cardiac troponin T (cTnT) have been investigated for noninvasive assessment of reperfusion. It is hoped that further studies will help refine the clinical use of new biomarkers like hs-cTn immunoassays in myocardial injury. [Med-Science 2017; 6(1.000): 163-71]

Cecal ligation and puncture (CLP) is a commonly used model of sepsis in vivo. We investigated the effects of dexpanthenol (DXP) on heart, lung and aorta in CLP-induced sepsis in rats. Rats were divided into four groups of eight: group 1, sham (SH); group 2 (DXP), 500 mg/kg DXP injected intraperitoneally (i.p.); group 3 (CLP), CLP performed; group 4 (CLP + DXP), 500 mg/kg DXP injected i.p. after CLP. Heart, lung and aorta specimens were harvested for histopathological and biochemical analysis. Heart rate increased in group 3 compared to group 1; DXP administration to group 4 did not alleviate this change. In heart tissue samples, MDA levels were decreased significantly in groups 2 and 4 compared to group 3. The levels of GSH in groups 2 and 3 were elevated compared to groups 1 and 2. SOD activity was increased significantly in group 4 compared to group 3. CAT activity for group 4 was increased significantly compared to groups 1 and 3. We found that caspase-9 and caspase-3 activity was increased after application of CLP. Also, DXP treatment decreased the number of caspase-positive cells significantly compared to group 3. DXP appears to be promising for reducing sepsis-related mortality.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

This study investigated the protective effects of Compound 21 (C21), the first specific non-peptide AT2 receptor agonist, on cardiac injury in rats with isoproterenol-induced heart failure in vivo and compared it with valsartan, an AT1 receptor antagonist. In this study, 56 Wistar albino male rats (estimated body weights 250–400 g) were divided into eight groups (n = 7). Group 1 (Control) received no drug. Group 2 (ISO) was given 180 mg/kg of isoproterenol subcutaneously (s.c.); two doses were administered at 24-h intervals on days 29 and 30 of the experiment. Groups 3, 4, and 5 were given valsartan (30 mg/kg orally), C21 (0.03 mg/kg intraperitoneally), and a combination of Valsartan + C21, respectively, for 30 days. Groups 6, 7, and 8 were administered Valsartan, C21, and Valsartan + C21 in the same application, duration, and dose, respectively, and isoproterenol (180 mg/kg s.c.) was given on days 29 and 30 of the experiment. Transthoracic echocardiography was performed on the rats at the beginning and end of the experiment. Blood pressure, heart rate, and ECG alterations were monitored via a carotid artery cannula at the end of the experiment. Histopathological and biochemical measurements were performed on the cardiac tissue of the rats. For histopathological findings, C21 and Valsartan + C21 combination therapy significantly reduced the development of heart failure compared to valsartan alone. Also, the protective effect of C21 on myocardial injury was superior to that of valsartan. According to the results of echocardiographic and biochemical evaluations, C21, and Valsartan showed protective effects against heart failure. C21, valsartan, and combined therapy significantly prevented the decrease of ejection fraction. This report describes the cardioprotective effects of C21 and valsartan in ISO-induced myocardial damage.

Aim: Although there are some treatment options for glucocorticoid induced osteoporosis (GIO), new drug alternatives are still needed. In this study, we aimed to determine the protective effects of misoprostol and melatonin in an experimental GIO model.Methods: The rats were grouped into four, with 10 rats in each group. The 1st group was chosen as the control group, which were not intervened with. Group 2 was the steroid group, group 3 the misoprostol group and group 4, the melatonin group. To the rats in groups 2, 3 and 4, 10 mg/kg subcutaneous methylprednisolone was administered for 28 days. To the rats of the 3rd group, 200 mg/day misoprostol was given per day by a cannula to the stomach. The rats in the 4th group received 5mg/kg intraperitoneal melatonin during this 28-days period. Lumbar vertebrae and femur bone mineral density (BMD) of all rats were measured by Dual-energy X-ray absorptiometry (DEXA) and assessed in pre- and post-treatment periods.Results: In the steroid group, when the pre- and post-treatment-BMD values of the rats were compared, statistically significant decreases were found in vertebrae, whole femur, femur proximal, femur diaphysis and distal femur bone regions (P=0.011, P=0.005, P=0.007, P=0.005 and P=0.013; respectively). In the misoprostol group, a statistically significant decrease was observed only in the whole femur region (P=0.012) when the pre- and post-treatment BMD values of the rats were compared, while no significant changes were observed in vertebrae, femur proximal, femur diaphysis and distal femur bone regions (P=0.093, P=0.401, P=0.161 and P=0.123; respectively). In the melatonin group, when the pre- and post-treatment BMD values of the rats were compared, a statistically significant decrease was observed only in the vertebrae region (P=0.009), no significant changes were observed in whole femur, femur proximal, femur diaphysis and distal femur bone regions (P=0.386, P=0.445, P=1.000 and P=0.483; respectively). Conclusion: Positive effects of misoprostol and melatonin on bone metabolism were determined in this experimental study. Misoprostol and melatonin seem to be potential agents that can be used in the prevention of GIO., Amaç: Glukokortikoid kaynaklı osteoporoz için kullanılan bazı tedavi seçenekleri olsa da, yeni ilaç alternatiflerine hâlâ ihtiyaç duyulmaktadır. Çalışmamızda ratlarda glukokortikoid kaynaklı osteoporoz modelinde misoprostol ve melatoninin koruyucu etkilerini belirlemeyi amaçladık.Yöntemler: Ratlar her grupta 10'ar adet olacak şekilde dört gruba ayrıldı: Grup1 kontrol, grup 2 steroid, grup 3 misoprostol, grup 4 melatonin grubu olarak belirlendi. Grup 2, 3, 4’teki ratlara 28 gün boyunca 10 mg/kg/gün subkutan metilprednizolon uygulandı. Grup 3’teki ratlara ilave olarak 200 mg/gün orogastrik misoprostol, grup 4’teki ratlara ilave olarak 5 mg/kg/intraperitoneal melatonin uygulandı. Tüm ratların lomber vertebra ve femur kemik mineral yoğunluğu DEXA yöntemi ile ölçülerek tedavi öncesi ve sonrası değerler karşılaştırıldı.Bulgular: Steroid grubunda, çalışma sonrası vertebra, tüm femur, femur proximal, femur diaphysis ve distal femur kemik mineral yoğunluğu değerleri istatistiksel olarak anlamlı derecede düşük bulundu (sırasıyla; P=0,011, P=0,005, P=0,007, P=0,005 ve P=0,013). Misoprostol grubunda sadece tüm femur bölgesinde çalışma sonrası kemik mineral yoğunluğu düşük (P=0,012) olup vertebra, femur proximal, femur diaphysis ve distal femur bölgeleri osteoporozdan korunmuştu (sırasıyla; P=0,093, P=0,401, P=0,161 ve P=0,123). Melatonin grubunda sadece vertebra bölgesinde çalışma sonrası kemik mineral yoğunluğu düşük (P=0,009) olup tüm femur, femur proximal, femur diaphysis ve distal femur bölgelerinde osteoporozdan korunmuştu (sırasıyla; P=0,386, P=0,445, P=1,000 ve P=0,483).Sonuç: Bu deneysel çalışmada misoprostol ve melatoninin kemik metabolizması üzerindeki olumlu etkileri belirlenmiştir. Misoprostol ve melatonin GIO’nun önlenmesinde kullanılabilecek potansiyel ajanlar gibi görünmektedir.

Background The aging process is not univocal, both body and brain age. Neurological disorders are a major cause of disability and death worldwide. According to the Global Burden of Disease Study 2015, neurological diseases are the second most common cause of death and 16.8% of total deaths are caused by neurological diseases worldwide. Neurological disease deaths have risen 36% worldwide in 25 years. Melatonin is a neuroregulator hormone that has free radical scavenger, strong antioxidant, anti-inflammatory, and immunosuppressive actions. These major properties of melatonin can play an important role in the pathophysiological mechanisms of neurological diseases. In addition, melatonin is necessary for circadian rhythm. Studies have shown that melatonin levels are low in people with neurological diseases. Both preventive and therapeutic effects of melatonin are known for many diseases, including neurological diseases (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, epilepsy, headache, etc.). Based on all these reasons, clinical trials of melatonin were performed and successful results were declared. Conclusions In this review, biological and chemical knowledge of melatonin, its experimental effects, and the clinical impact on patients with neurological disorders were described. According to all of the beneficial results obtained from experimental and clinical trials, melatonin may have a prophylactic and therapeutic effect on neurological diseases. Strong collaboration between neurologists and health service policy makers is needed to encourage use of melatonin in the patients suffering from neurological diseases. Melatonin may be the solution we have been looking for.

Background: Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. Aims: The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. Study Design: Animal experiment. Methods: The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. Results: During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42nd day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p

This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study.A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out.Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations.This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental.Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas.Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas.Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar.

Parlakpinar, Hakan/0000-0001-9497-3468; Tutun, Bugra/0000-0002-3803-0489 WOS: 000467970800001 PubMed ID: 30317873 Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress contributes to the development of diabetic complications. Dexpanthenol (Dxp) is the biological active form of pantothenic acid. We investigated whether Dxp administration could decrease oxidative stress as a way to treat renal complications of diabetes mellitus (DM). Thirty-two male Wistar albino rats were divided into four groups: control, Dxp, DM and DM + Dxp. Experimental diabetes was induced by a single dose of streptozotocin (STZ). After administration of STZ, the DM + Dxp group was administered 500 mg/kg Dxp intraperitoneally every day for 6 weeks. At the end of the study, blood glucose levels were measured and rats were sacrificed. Kidneys were embedded in paraffin, sectioned and stained with hematoxylin and eosin, and periodic acid-Schiff. The mean malondialdehyde levels, glutathione peroxidase, superoxide dismutase and catalase activities, and total antioxidant and total oxidant status also were measured. The control group was normal in histological appearance. We observed congestion, inflammation, glomerulosclerosis, tubular desquamation, loss of villi and hydropic degeneration in tubule cells in the DM group. Indicators of oxidative stress were elevated and antioxidant activity was reduced in the DM group compared to controls. In the DM + Dxp group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced compared to the DM group. We found that Dxp exhibited ameliorative effects on STZ induced diabetic nephropathy by increasing antioxidant activity. Turkish Scientific and Technological Research Council (TUBITAK) under Domestic University Students Research Projects Support Programme [2209-A/2012] Our project was supported by Turkish Scientific and Technological Research Council (TUBITAK) under Domestic University Students Research Projects Support Programme, 2209-A/2012.

Aim: Postoperative pelvic adhesions (PPAs) are a common complication that leads to many problems. This study aimed to compare the role of Seprafilm (a protective barrier), and molsidomine (MOL), recognized for its antioxidative and antiproliferative effects, in preventing pelvic adhesion. Material and Methods: A total of 30 of female Wistar albino rats were randomly divided into 3 groups. They underwent bilateral uterine horn injury. The rats in the Sham group (n=10) received no special treatment. The rats in the Seprafilm group (n=10) were treated withSeprafilm. The rats in the MOL group (n=10) received 10 mg/kg MOL orally for 14 days. Adhesion scores were evaluated using macroscopic, microscopic, and immunohistochemical grading 14 days postoperatively. Results:The Majuzi adhesion score of the rats in the MOL group [1 (0-4)] was lower than the score of the rats in the sham [4 (2-5)] and Seprafilm [4 (1-5)] (p

Background and aim It has been reported that intestinal ischemia-reperfusion (I/R) injury results from oxidative stress caused by increased reactive oxygen species. Dexpanthenol (Dxp) is an alcohol analogue with epitelization, anti-inflammatory, antioxidant, and increasing peristalsis activities. In the present study, the aim was to investigate protective and therapeutic effects of Dxp against intestinal I/R injury. Materials and methods Overall, 40 rats were assigned into five groups including one control, one alone Dxp, and three I/R groups (40-min ischemia; followed by 2-h reperfusion). In two I/R groups, Dxp (500mg/kg, i.m.) was given before or during ischemia. The histopathological findings including apoptotic changes, and also tissue and serum biochemical parameters levels, were determined. Oxidative stress and ileum damage were assessed by biochemical and histological examination. In the control (n=8) and alone Dxp (n=8; 500mg/kg, i.m. of Dxp was given at least 30min before recording), groups were incised via laparotomy, and electrical activity was recorded from their intestines. In this experiment, the effect of Dxp on the motility of the intestine was examined by analyzing electrical activity. Results In ileum, oxidant levels were found to be higher, while antioxidant levels were found to be lower in I/R groups when compared with controls. Dxp approximated high levels of oxidants than those in the control group, while it increased antioxidant values compared with I/R groups. Histopathological changes caused by intestinal I/R injury and histological improvements were observed in both groups given Dxp. In the Dxp group, electrical signal activity markedly increased compared with the control group. Conclusions Here, it was seen that Dxp had protective and therapeutic effects on intestinal I/R injury and gastrointestinal system peristaltism.

Dexpanthenol (Dxp) plays a major role in cellular defense and in repair systems against oxidative stress and inflammatory response and it has not yet been evaluated in treatment of bronchopulmonary dysplasia (BPD). We tested the hypothesis that proposes whether Dxp decreases the severity of lung injury in an animal model of BPD.Forty rat pups were divided into four groups: control, control + Dxp, hyperoxia and hyperoxia + Dxp. All animals were processed for lung histology and tissue analysis. The degree of lung inflammation, oxidative and antioxidant capacity was assessed from lung homogenates.Lung injury score and alveol diameter increased in the hyperoxia group (p 0.001). Median level of malondialdehyde, total oxidant status and oxidative stress indexes was significantly higher in the hyperoxia group compared to the other groups. The median superoxide dismutase activity in the hyperoxia group was notably less than those of control + Dxp and hyperoxia + Dxp groups (p 0.01). Similarly, lung catalase, glutathione (GSH) peroxidase and reduced GSH activities in the hyperoxia group were significantly lower than other groups. Furthermore, the hyperoxia + Dxp group had lower tumor necrosis factor-α and interleukin-1β median levels compared to the hyperoxia group (p = 0.007).Dxp treatment results in less emphysematous change as well as decrease in inflammation and oxidative stress markers in an animal model of BPD.

We investigated the protective effect of the NADPH oxidase inhibitor apocynin on testicular damage induced by ischemia-reperfusion injury in rats.A total of 32 rats were randomly divided into 4 groups. Controls underwent left scrotal exploration only. The 3 groups with ischemia-reperfusion underwent 4-hour torsion followed by 1-hour detorsion. The ischemia-reperfusion only group underwent left testicular torsion and detorsion. The ischemia-reperfusion plus saline group underwent left testicular torsion, received 10 ml/kg saline intraperitoneally at minute 210 of ischemia and then underwent detorsion. The ischemia-reperfusion plus apocynin group underwent left testicular torsion, received 20 mg/kg apocynin intraperitoneally at minute 210 of ischemia and then underwent detorsion. We determined histopathological findings and performed specific biochemical analyses.In the ischemia-reperfusion only and the ischemia-reperfusion plus saline groups malondialdehyde, total oxidative capacity and the oxidative stress index were significantly higher. Superoxide dismutase, catalase, glutathione peroxidase and glutathione were significantly lower. Apocynin significantly decreased malondialdehyde, total oxidative capacity and the oxidative stress index, and significantly increased superoxide dismutase and catalase. There was a significantly increase in the number of giant, degenerated and desquamated cells in the ischemia-reperfusion group. Apocynin significantly improved these histological alterations.These histopathological and biochemical findings show the beneficial effects of apocynin on testicular ischemia-reperfusion injury.

Parlakpinar, Hakan/0000-0001-9497-3468; Ozhan, Onural/0000-0001-9018-7849 WOS: 000435663500004 PubMed: 29323543 We investigated the effect of molsidomine (MOL) on ischemia/reperfusion (I/R) injury. Rabbits were assigned to four groups: group 1, sham; group 2, I/R; group 3, MOL treatment for 4days after I/R; group 4, MOL treatment for 1 day before I/R and 3days after I/R. Retinal I/R was produced by elevating the intraocular pressure to 150mm Hg for 60min. Seven days after I/R, the eyes were enucleated. Retinal changes were examined using histochemistry. The levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) also were measured. We found a significant increase in the thickness of the outer nuclear layer of group 3 compared to the other groups. In groups 3 and 4, caspase-3 stained cells in the ganglion cell layer were decreased compared to group 2. We found a significant increase in caspase-3 stained cells in the inner nuclear layer (INL) of group 2 compared to the other groups. We found a significant increase in caspase-3 stained cells in group 3 compared to group 4 in the INL. The MDA level in group 2 was significantly higher than group 1 and MOL significantly decreased MDA levels in groups 3 and 4. We found that MOL protected the retina from I/R injury by enhancing antioxidative effects and inhibiting apoptosis of retinal cells.

Preventive and/or therapeutic interventions for ischemic heart disease have gained considerable attention worldwide. We investigated the mechanism(s) underlying cardioprotection of apocynin (APO) and whether it attenuates isoproterenol (ISO)-induced myocardial damage in vivo. Thirty-two male Wistar Albino rats were randomised into four groups (n = 8 for each group): Group I (Control); Group II (ISO), ISO was given intraperitoneally (ip) (150 mg/kg/d) daily for 2 consecutive days; Group III (APO + ISO), APO was applied ip 20 mg/kg 30 min before the first ISO administration and continued for the next 2 d after the second ISO administration; Group IV (ISO + APO), after the ISO treatment on days 1 and 2, 20 mg/kg APO was given ip on days 3 and 4. Cardioprotective effects of APO were evaluated by biochemical values, histopathological observations and the antiapoptotic relative proteins. Mean blood pressure, heart rate, and electrocardiography (ECG) were also monitored. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), caspase-3 and connexin 43 levels were determined. Major ECG changes were observed in the ISO-treated rats. MDA, TOS, OSI and creatine kinase levels decreased and SOD, CAT, GSH and TAC levels increased, indicating that APO reduced cardiac injury and oxidative stress compared with controls. APO also decreased the number of cardiomyocytes with pyknotic nuclei, inflammatory cell infiltration, intracytoplasmic vacuolisation and myofibrils. APO provides preventive and therapeutic effects on ISO-induced myocardial injury in rats by inhibiting reactive oxygen species production, blocking inflammation and enhancing antioxidant status.

A lot of mechanisms play major role in the myocardial ischemia reperfusion injury (MI/R), especially reactive oxygen species (ROS) which they formed rapidly when molecular oxygen enters into the cell. Melatonin, major hormone of the pineal gland, has very strong antioxidant and free radical scavenger effects. Besides, melatonin plays an important role in the regulation of various body functions including circadien sleep rhythms, blood pressure, oncogenesis, retinal function, and immunity. It can be possible to say that oxidative stress occurs during MI/R and melatonin administration exerts an infarct size limiting effect, antiapoptic, antiarryhtmic effects and enhances antioxidant activity of the heart. Key words: Myocardial ischemia-reperfusion, free radicals, no-reflow, necrosis, antioxidants

Parlakpinar, Hakan/0000-0001-9497-3468 WOS: 000343651400028 PubMed: 24913463 Purpose The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis. Methods Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups. Results Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-alpha levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05). Conclusion Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosis through its anti-inflammatory and anti-nociceptive properties.

Objective: In this experimental study, we aimed to investigate the role of melatonin on uterine myoelectrical activity of non-pregnant rats.Material and Methods: Forty-six female rats were assigned to six groups: (1) control; (0.2 mL 0.9% NaCl was injected intravenously (IV), n=6); (2) melatonin applied as 0.4 mg/kg/IV (n=8); (3) melatonin applied as 4 mg/kg/IV (n=8); (4) single dose of oxytocin (100 mU/kg) injected IV (n=8); (5) melatonin (0.4 mg/kg) plus oxytocin (100 mU/kg) (n=8); and (6) melatonin (4 mg/kg) plus oxytocin (100 mU/kg) injected IV (n=8). Each rat underwent a laparotomy, and uterine myoelectrical signals were recorded. The mean spectrum, averaged over the spectral content of signals in each group, was compared.Results: Melatonin induced uterine myoelectrical activity in a dose-dependent manner. Treatment of melatonin after oxytocin suppressed the mean power of the signals. Serum melatonin concentrations were significantly higher in melatonin-treated rats.Hypoparathyroidism, deafness, and renal dysplasia (HDR; OMIM 146255) syndrome is a rare disease, inherited dominantly and found to be related with GATA3 (GATA binding protein 3) gene mutations. A 13-year and 8-month-old boy who presented with hypocalcemia was diagnosed with hypoparathyroidism. He also had dysmorphic facial features, renal anomaly (pelvic kidney), and mild sensorineural hearing loss. His cranial computed tomography revealed multiple calcifications in bilateral centrum semiovale, corona radiata, and basal ganglions suggesting a persistent hypoparathyroidism. Thus, the presence of triad of HDR syndrome was considered, and genetic analysis using a next-generation sequencer identified a novel de novo missense mutation in exon 4 p.R276Q (c.827G>A) of GATA3 gene. This is the second patient who was reported to have a mutation in GATA3 gene from Turkey. In conclusion, although HDR syndrome is a rare condition, it should be kept in mind in patients with hypoparathyroidism. Classical triad can easily be identified if patients diagnosed with hypoparathyroidism are also evaluated with a urinary tract ultrasound and an audiometer.

ObjectiveThe aim of this study was to assess if perineural administration of dexmedetomidine combined with levobupivacaine increases the duration of the sensory and motor blockade of a sciatic peripheral nerve block in rats.MethodsForty male Sprague–Dawley rats were randomly divided into 5 experimental groups: Group 1, sham; Group 2, perineural levobupivacaine (0.2 mL of a 0.5% solution) and subcutaneous saline; Group 3, perineural levobupivacaine (0.2 mL of a 0.5% solution) plus dexmedetomidine (20 µg/kg dexmedetomidine) and subcutaneous saline; Group 4, perineural saline and subcutaneous dexmedetomidine; and Group 5, perineural saline and subcutaneous saline. Pain reflexes in response to a thermal stimulus were measured at 0 and 240 minutes after drug administration by using a hot-plate and tail-flick tests. Neurobehavioral status, including sensory and motor functions, was assessed by an investigator who was blinded to the experimental groups every 30 minutes until normal functioning resumed.ResultsThe sensory and motor blockades of the rats did not increase in the treatment with dexmedetomidine plus levobupivacaine when compared with the treatment with levobupivacaine alone at all the time points (P > 0.05). Compared with rats in Group 2, those in Group 3 showed significantly higher latency times at 30 and 60 minutes in the hot plate test (P < 0.01). At 30 and 60 minutes, the latency times of the rats in Group 3 were longer than those in Group 2 in the tail-flick test (P < 0.01). Furthermore, the durations of the complete sensory and motor blockade were similar when treatment with levobupivacaine plus dexmedetomidine was compared with treatment with levobupivacaine alone.ConclusionsA 20µg/kg dose of dexmedetomidine added to levobupivacaine did not increase the duration of the sensory and motor blockades in rats. However, treatment with dexmedetomidine plus levobupivacaine increased the quality of analgesia in rats.

We investigated the protective and therapeutic effects of molsidomine (MOL) in a rat model of whole brain radiotherapy (RT). Forty female rats were divided into five groups of eight: group 1, control; group 2, 15 Gy single dose RT (RT); group 3, 4 mg/kg MOL treated for 5 days (MOL); group 4, 4 mg/kg MOL for 5 days, 10 days after RT treatment (RT + MOL); group 5, 4 mg/kg MOL treatment for 5 days before RT treatment and for 5 days after RT treatment (MOL + RT). All rats were sacrificed on day 16. Neurodegenerative changes in the brain and tissue levels of oxidants and antioxidants were evaluated. The oxidative parameters were increased and antioxidant status was decreased in group RT compared to groups MOL + RT and RT + MOL. Histopathological examination showed that treatment with MOL after RT application and treatment with MOL before RT treatment decreased neuronal degeneration. No difference in neuronal appearance was found between groups RT + MOL and MOL + RT. MOL treatment protected the nervous system of rats and may be a treatment option for preventing RT induced neural injury.

Parlakpinar, Hakan/0000-0001-9497-3468; OZER, MURAT ATABEY/0000-0003-1807-6911 WOS: 000400977100023 PubMed: 27897441 Purpose: To determine the role of Molsidomine in preventing radiation-induced retinopathy after head and neck region irradiation of rats with a single radiation dose of 15 Gy. Materials and Methods: Male Wistar albino rats were randomly grouped into five as follows: (1) control group rats, which were applied through an intraperitoneal (i.p.) vehicle without radiotherapy (RT); (2) RT group rats received a single dose of 15 Gy irradiation and after daily 0.1 ml vehicle i.p. for 5 consecutive days; (3) molsidomine (MOL) group rats were treated for 5 consecutive days by i.p. with 4 mg/kg/day MOL; (4) irradiation plus MOL group (RT+MOL) rats received irradiation and after 10 days single daily i.p. dose of MOL for 5 consecutive days; and (5) MOL+RT group rats were treated for 5 consecutive days by i.p. with MOL before RT. At the end of the work the rats were sacrificed under high-dose anesthesia on the 16(th) day and then eye tissues were taken for histopathological, immunohistochemical (caspase-3), and biochemical analyses (superoxide dismutase [SOD], glutathione peroxidase [GSH], and malondialdehyde [MDA]). Results: RT significantly decreased both the content of GSH and the activity of SOD, and significantly increased the production of MDA level in the rat eyes. MOL treatment significantly increased the SOD and GSH levels and significantly decreased the MDA production (p < 0.0001). In addition, RT significantly increased the number of ganglion cells (GCs; p = 0.001), whereas especially pretreatment with MOL improved (p = 0.013). RT led to significant retinopathy formation, and MOL therapy protected the retina from radiation-induced retinopathy (p < 0.0001). Conclusions: We suggest that MOL is a powerful antioxidant and free radical scavenger that prevents the rat eyes from radiation-induced retinopathy and oxidative stress.

Parlakpinar, Hakan/0000-0001-9497-3468; OZER, MURAT ATABEY/0000-0003-1807-6911 WOS: 000401918500022 PubMed: 27495951 The aim of the current study was to evaluate the effect of apocynin (APO) on the development of proliferative vitreoretinopathy (PVR). New Zealand-type male rabbits were randomly grouped into three as follows: (1) Sham group rabbits which were applied intraperitoneal (i.p.) vehicle without PVR; (2) PVR group rabbits where PVR was created and an i.p. vehicle was administered for 21 successive days; (3) PVR + APO group rabbits where PVR was created and i.p. APO was administered for 21 successive days. Fundus examination was conducted with an indirect ophthalmoscope before starting the experiments and at each visit afterwards. At the end of the work, the rabbits were sacrificed under high-dose anesthesia and then eye tissues were taken for histopathological analyses. In the PVR + APO group, histopathologic and ophthalmoscopic examination revealed significant decrease in PVR formation. As the result, it has been observed that APO at least partially inhibits PVR formation.

Although melatonin has been implicated in several neurophysiological systems, data on the relationship of melatonin with psychosis such as schizophrenia are limited and contradictory. Chronic effects of melatonin on sensorimotor gating deficits have also not been investigated yet. We investigated the neurobehavioral effects of chronic administration of melatonin in pinealectomized (Px) and ovariectomized (Ovx) rats. Px or Ovx or both operations were carried out together to the rats. The control group of rats was sham operated. A sham ovariectomy was carried out to Px rats, and vice versa. Fifth month later, melatonin (5 mg/kg) or vehicle was injected to rats for 28 days. Then, prepulse inhibition (PPI) of acoustic startle reflex, startle amplitude and startle reflex latency was measured. Locomotor activity, accelerod performance measurements, novel object recognition and passive avoidance tests were also evaluated. Px and Px + Ovx rats had impaired PPI compared to control rats. Melatonin reversed the impairments of PPI induced by Px or Px + Ovx. While melatonin treatment had no effect on locomotor activity of control rats, it significantly increased the locomotor activity of Px and Px + Ovx rats. Melatonin treatment (5 mg/kg/day, 28 days) reversed the locomotor hyperactivity caused by Ovx. Accelerod performance, passive avoidance, and object recognition responses of Px, Ovx or Px + Ovx rats were not different from the control group. Our results indicate that chronic melatonin deficiency by reason of Px results in impairment of PPI reflex and replacement of melatonin exerts beneficial effects on the impaired PPI reflex in Px and Ovx rats. Thus, melatonin may be useful in the treatment of some disorders characterized by sensorimotor gating deficits such as schizophrenia. (C) 2012 Elsevier B.V. All rights reserved.

Purpose: To explore the protective and curative effects of molsidomine (MOL) on doxorubicin (DOX)-induced cardiac damage in the in vivo rat heart. Methods: Forty rats were randomized into five groups (n = 8): (1) the control group; (2) the MOL group (10 mg/kg for 21 days); (3) the DOX group (a single dose of 20 mg/kg); (4) the DOX + MOL group (3 days after the single dose of DOX, 10 mg/kg MOL continued for 21 days), and (5) the MOL + DOX group (24 h after a 21-day regimen of 10 mg/kg MOL, a single dose of DOX). The rats were monitored for mean arterial blood pressure, heart rate, O2 saturation, and electrocardiography. Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and nitric oxide (NO) were determined. Results: Blood pressure and O2 saturation values indicated a significant decrease in the DOX group compared with the control group. T negativity was observed in 4 of 8 rats in the DOX group, in 1 of 8 rats in the DOX + MOL group, and in 4 of 8 rats in the MOL + DOX group. MDA levels were significantly higher in the DOX group. SOD, GSH, and NO levels were significantly lower in the DOX group compared with the other groups. There was no statistically significant difference in the CAT levels in any of the study groups compared with controls. DOX treatment induced morphological alterations, such as disorganization of cardiomyocytes, loss of myofibrils, and cytoplasmic vacuolization in the heart. On the other hand, histological damage was significantly reduced in the DOX + MOL and MOL + DOX groups. Conclusion: This study implies that there are cardioprotective effects of MOL on DOX-induced cardiotoxicity.

OBJECTIVE The objective of this study was to compare the effects of two drugs on motor performance and analgesic efficacy in a rat model. MATERIAL AND METHODS Rats were randomly divided into four groups as follows: propofol (600 μg/kg/min), dexmedetomidine (1 μg/kg/min), morphine (83 μg/kg/min) and control. The rats were placed on a rotating rod and tested at the slowest speed (5 rpm) and then at increasing increments from 5, 10, 15, 20, 25, 30, 35 to 40 rpm. The speed was set up again from 1 to 79 rpm within 4 and 10 min for the accelerod test, respectively. Pain reflexes in response to a thermal stimulus were measured at 0, 10, 20 and 60 min after the drug injection using the hot-plate test. RESULTS Dexmedetomidine injected rats showed an increased length of time compared to the propofol group at 20 rpm, 25 rpm, 35 rpm and 40 rpm speeds during the rotarod test. The latency times for the hot-plate test increased significantly for the propofol, at 0, 10 and 20 min compared to the control. At 10 min the latency times of the propofol group were longer than the dexmedetomidine group. CONCLUSIONS For long-term analgesic benefit propofol treatment seems to be better than the dexmedetomidine group. Dexmedetomidine may be preferable in day-case surgery and sedation applications in intensive care units as it provided a faster onset of recovery of motor coordination performance.

Objective: To determine the protective effects of hyaluronic acid and chondroitin sulfate in treating urinary tract infections in a rat model. Methods: A total of 28 rats, which were induced with urinary tract infections through intravesical administration of Escherichia coli, were included in the study. By random selection, they were equally divided into four groups as control (no treatment), hyaluronic acid, chondroitin sulfate and hyaluronic acid + chondroitin sulfate. Bacteriological cultures of the urine and bladder tissue samples were carried out, and the data for each group were statistically compared. Results: In the urine cultures, there were significant differences in median bacterial growth rates in hyaluronic acid (5 × 103 cfu/mL) and chondroitin sulfate (1 × 104 cfu/mL) groups relative to the control group (5 × 104 cfu/mL). However, a significantly lower rate of bacterial colony growth was observed in the hyaluronic acid + chondroitin sulfate group (8 × 102 cfu/mL; P

The researchers need to be aware of the design, methodology, analysis and interpretation of the studies to assess effectively the results of animal experiments. This can be achieved with the published research standards or guidelines. ARRIVE guidelines (Animals in Research: Reporting In Vivo Experiments) have been published to improve the quality and transparency of studies of animal experiments in the British Journal of Pharmacology in 2010. This study was carried out to review the studies related to ARRIVE guidelines. Key words: ARRIVE Guidelines; Animal Experiments; Checklist.

Effects of electromagnetic energy radiated from mobile phones (MPs) on heart is one of the research interests. The current study was designed to investigate the effects of electromagnetic radiation (EMR) from third-generation (3G) MP on the heart rate (HR), blood pressure (BP) and ECG parameters and also to investigate whether exogenous melatonin can exert any protective effect on these parameters. In this study 36 rats were randomized and evenly categorized into 4 groups: group 1 (3G-EMR exposed); group 2 (3G-EMR exposed + melatonin); group 3 (control) and group 4 (control + melatonin). The rats in groups 1 and 2 were exposed to 3G-specific MP’s EMR for 20 days (40 min/day; 20 min active (speech position) and 20 min passive (listening position)). Group 2 was also administered with melatonin for 20 days (5 mg/kg daily during the experimental period). ECG signals were recorded from cannulated carotid artery both before and after the experiment, and BP and HR were calculated on 1st, 3rd and 5th min of recordings. ECG signals were processed and statistically evaluated. In our experience, the obtained results did not show significant differences in the BP, HR and ECG parameters among the groups both before and after the experiment. Melatonin, also, did not exhibit any additional effects, neither beneficial nor hazardous, on the heart hemodynamics of rats. Therefore, the strategy (noncontact) of using a 3G MP could be the reason for ineffectiveness; and use of 3G MP, in this perspective, seems to be safer compared to the ones used in close contact with the head. However, further study is needed for standardization of such an assumption.