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We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.

Methotrexate (MTX) is an important drug for rheumatic and non-rheumatic disease therapy. MTX has been associated with many adverse effects ranging from asymptomatic transaminase elevation to fibrotic tissue formation and fatal hepatic necrosis due to oxidative stress. Concerns regarding potential liver toxicity have led to the avoidance of medication, termination, or advice for inquiries in clinical care. The protective and therapeutic effects of a new generation anti-angina drug, ranolazine (RAN), on MTX-induced liver damage were investigated by evaluating its antioxidant mechanism in rats. Thirty-two female Wistar Albino rats were randomly assigned to Control, RAN, prophylaxis, and treatment groups (n=8/group). Liver function enzymes, histopathological assessment and serum biochemical parameters were examined. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were also measured in liver tissue. MTX administration caused mononuclear inflammation, vascular congestion, ductal proliferation, vacuolization, and fibrosis as evaluated using Roening grading and increases in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase levels ( ppp>0.05). According to our results, RAN may be a potential hepatoprotective agent against MTX-induced liver injury.

Cisplatin (CIS)-induced nephrotoxicity is associated with oxidative stress, apoptosis, inflammation, and fibrogenesis. In this study, we investigated the therapeutic effects of ranolazine (RAN), a current antianginal drug known to experimentally reduce oxidative damage in CIS-induced nephrotoxicity. We randomly assigned thirty-two Sprague Dawley rats to one of four groups (Control, CIS, CIS+RAN, and RAN+CIS). We evaluated kidney function parameters including blood urea nitrogen (BUN), creatinine (Cre), electrolytes, and albumin, as well as tissue biochemical parameters including malondialdehyde (MDA) and antioxidant enzymes. Histopathological parameters were also assessed. We observed a significant increase in BUN and Cre values in the CIS group compared to the control group (p0.05), and serum electrolytes were comparable among groups. Furthermore, a statistically significant increase in albumin levels was observed in the CIS+RAN group compared to the CIS group (p0.05). Our findings suggest that the beneficial effects of RAN on CIS-induced nephrotoxicity may be related to its antioxidant activity.

The use of JWH-018, which is among the abused bonsai in the world and in our country due to its psychostimulant effect, is increasing day by day. Here, we evaluated the pharmacologic, cardiologic, biochemical, and histopathological effects of acute and subacute administration of low and high doses of JWH-018 in rats. The concentrations of JWH-018 and its metabolites in the heart were analyzed by liquid chromatography-mass spectrometry. JWH-018 administration caused many cardiac pathologies including dysregulation of the heart rate, and low blood pressure, also induced cardiac arrhythmia, branch blocks, and ischemic ECG changes depending on the drug dosage and the duration of treatment. Echocardiography did not show any significant structural or functional changes among the groups. The level of serum pro-brain natriuretic peptide which is an indication of impaired cardiac capabilities become observed to be elevated in a long-time excessive dose JWH-018 used group. Histopathologic findings consistent with acute myocardial ischemia were detected in the hearts of all groups. Loss of cross-talk of myocardial fibrils, and prominent eosinophilic contraction bands were early signs of acute myocardial infarction (4th and 12th hours), which were more common in subacute groups and associated with ischemia. Desmin staining was observed as increased in subacute groups and there were marked contraction band dyneins. There is growing pharmacological and pathological evidence of impairment, cardiac effects, and tissue injury attributable to this emerging class of drugs.

Hard or soft tissue adhesives have been presented as a promising candidate to replace traditional wound closure methods. However, there are mechanical strength problems in biological adhesives and biocompatibility problems in synthetic-based adhesives. At this point, we aimed to remove all these disadvantages and produce a single adhesive that contains all the necessary features and acrylate functionalized UV-curable polyurethane formulations were produced with high crosslink density, high adhesion strength, biocompatibility and injectable property for easy application as potential biomedical adhesives. Aliphatic isophorone diisocyanate (IPDI) was used as the isocyanate source and β-cyclodextrin was used for host-guest relationship with gentamicin by crosslinking. Proteins (gelatin (GEL), collagen (COL)) and PEGs of various molecular weight ranges (P200, P400, P600) were selected as the polyol backbone for polyurethane synthesis due to their multiple biological activities such as biocompatibility, biodegradability, biomimetic property. Several techniques have been used to characterize the structural, thermal, morphological, and various other physicochemical properties of the adhesive formulations. Besides, the possibility of its use as a hard tissue adhesive was investigated by evaluating the tissue adhesion strength in vitro and ex vivo via a universal testing analyzer in tensile mode. Corresponding adhesive formulations were evaluated by in vitro and in vivo techniques for biocompatibility. The best adhesion strength results were obtained as 3821.0 ± 214.9, and 3722.2 ± 486.8 kPa, for IPDI-COL-P200 and IPDI-GEL-P200, respectively. Good antibacterial activity capability toward Escherichia coli Pseudomonas aeruginosa, and Staphylococcus aureus were confirmed using disc diffusion method. Moreover, cell viability assay demonstrated that the formulations have no significant cytotoxicity on the L929 fibroblast cells. Most importantly, we finally performed the in vivo biodegradability and in vivo biocompatibility evaluations of the adhesive formulations on rat model. Considering their excellent cell/tissue viability, fast curable, strong adhesion, high antibacterial character, and injectability, these adhesive formulations have significant potential for tissue engineering applications.

Heart failure (HF) is one of the most critical health and economic burdens worldwide, and its prevalence is continuously increasing. HF is a disease that occurs due to a pathological change arising from the function or structure of the heart tissue and usually progresses. Numerous experimental HF models have been created to elucidate the pathophysiological mechanisms that cause HF. An understanding of the pathophysiology of HF is essential for the development of novel efficient therapies. During the past few decades, animal models have provided new insights into the complex pathogenesis of HF. Success in the pathophysiology and treatment of HF has been achieved by using animal models of HF. The development of new in vivo models is critical for evaluating treatments such as gene therapy, mechanical devices, and new surgical approaches. However, each animal model has advantages and limitations, and none of these models is suitable for studying all aspects of HF. Therefore, the researchers have to choose an appropriate experimental model that will fully reflect HF. Despite some limitations, these animal models provided a significant advance in the etiology and pathogenesis of HF. Also, experimental HF models have led to the development of new treatments. In this review, we discussed widely used experimental HF models that continue to provide critical information for HF patients and facilitate the development of new treatment strategies.

Propolis is a resin like natural material that bees collect from various parts of plants. Bees use propolis as protective against various pathogens. Propolis has many biological effects due to its rich content. Perga is a fermented product of pollen and honey that bees use to feed their offspring. The aim of this study is to compare the perga, which is rich by phenolic compounds, to the propolis for its antimicrobial activity.Ethanolic extracts of the propolis and perga were prepared and total phenolic compound quantity determination were made according to the Folin-Ciocalteu method. The minimum inhibitory concentration (MIC) values of the extracts on Escherichia coli and Pseudomonas aeruginosa which are gram-negative pathogens, Staphylococcus aureus which is a gram-positive pathogen, and Candida albicans which is a fungus were measured by microdilution method. The MIC test range for propolis and perga was determined as 0.06µg/mL-125µg/mL, depending on the amount of phenolic compounds.Propolis showed an inhibitory effect at low concentrations against Candida albicans and Staphylococcus aureus compared to Escherichia coli and Pseudomonas aeruginosa. It has been determined that perga has an inhibitory effect at low concentrations against Escherichia coli, Pseudomonas aeruginosa and Candida albicans; although, it was determined that more higher concentrations are required for perga to show inhibitory activity against Staphylococcus aureus.As a result, it was observed that propolis and perga exhibited antimicrobial effects in our study., Propolis, arıların bitkilerin çeşitli kısımlarından topladığı reçine benzeri doğal bir maddedir. Arılar propolisi çeşitli patojenlere karşı koruyucu olarak kullanırlar. Propolis zengin içeriği sayesinde birçok biyolojik etkiye sahiptir. Perga, arıların yavrularını beslemek için kullandığı polen ve baldan oluşan fermente bir üründür. Bu çalışmanın amacı fenolik bileşiklerce zengin olan perganın, antimikrobiyal aktivitesinin propolisle karşılaştırılmasıdır. Propolis ve perganın etanolik ekstraktları hazırlandı ve Folin-Ciocalteu yöntemi ile toplam fenolik bileşik miktar tayini yapıldı. Ekstraktların gram-negatif patojenler olan Escherichia coli ve Pseudomonas aeruginosa, gram-pozitif bir patojen olan Staphylococcus aureus ve bir mantar türü olan Candida albicans üzerinde minimum inhibitör konsantrasyon (MİK) değerleri mikrodilüsyon yöntemi ile ölçüldü. Propolis ve perga için MİK test aralığı fenolik bileşik miktarına göre 0,06µg/mL-125µg/mL olarak belirlendi. Propolis, Escherichia coli ve Pseudomonas aeruginosa’ya göre Candida albicans ve Staphylococcus aureus’a karşı düşük konsantrasyonlarda inhibe edici etki göstermiştir. Perganın Escherichia coli, Pseudomonas aeruginosa ve Candida albicans’a karşı yine düşük konsantrasyonda inhibitör etki gösterdiği; ancak, perganın Staphylococcus aureus’a karşı inhibitör etkinlik gösterebilmesi için çok daha yüksek konsantrasyonlara ihtiyaç olduğu saptanmıştır. Sonuç olarak propolis ve perganın çalışmamızda antimikrobiyal etki gösterdiği izlenmiştir.

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.

Radiation hepatotoxicity is thought to be due to free oxygen radicals. We investigated the protective effects of apocynin (APO) against ionizing radiation induced oxidative stress in liver tissue following whole body ionizing radiation. We divided rats into four groups. The control group was injected intraperitoneally (i.p.) with saline for five consecutive days. A second group was injected i.p. with saline for 5 days and after 24 h, a single-dose of radiation (800 cGy) was administered to the whole abdomen. A third group was injected i.p. with 20 mg/kg APO for 5 days. A fourth group was injected i.p. with APO for 5 days and after 24 h, the rats were exposed to radiation. Ionizing radiation induced hepatotoxicity was demonstrated biochemically by significant changes in oxidative and antioxidant parameters. Our findings suggest that APO treatment may be protective against radiation induced hepatic injury by decreasing oxidative stress and increasing antioxidant activity.

The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin-angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II-induced hypertension in rats. Sprague Dawley rats were subject to 4-week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 μg/kg), AVE0991 (576 μg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail-cuff plethysmography at 1, 15, and 29 days post-treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin-A (CYP-A), monocyte chemoattractant protein-1 (MCP-1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase-2 and -9, NADPH oxidase-4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP-1 and CYP-A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin-converting enzyme-2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II-induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.

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...

Highlights Cisplatin is an antineoplastic agent used malignant diseases. Cisplatin ototoxicity is generally bilateral, irreversible, and progressive. Genistein is a phytoestrogen. Genistein functions as antioxidant and cell cycle inhibitor by inhibiting DNA topoisomerase. Genistein showed positive effects on ototoxicity with its antioxidant. Objective Cisplatin is an antineoplastic agent used in adults and children for the treatment of various malignant diseases. It can cause irreversible ototoxicity. Genistein is a phytoestrogen. Genistein functions as an antioxidant and cell cycle inhibitor by inhibiting the DNA topoisomerase and tyrosine protein kinase enzymes. The protective effect of genistein in preventing cisplatin-induced ototoxicity and levels of the oxidative stress was investigated. Methods 32 Sprague Dawley rats were used in 4 groups (control, cisplatin, cisplatin + genistein, genistein). Otoacoustic emission measurements of the distortion product were performed on the 1st, 2nd and 5th days of the test protocol. Serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, total antioxidant status, total oxidant status and oxidative stress index measurements were made. Results The hearing of the cisplatin + genistein group was found to be better than that of the cisplatin group. While the malondialdehyde, total oxidant status and oxidative stress index parameters decreased significantly in the cisplatin + genistein group compared to the cisplatin group, superoxide dismutase increased significantly (p < 0.05). Conclusion Genistein showed positive effects against ototoxicity with its antioxidant effect. Level of evidence Level 3. Resumo DESTAQUES A cisplatina é um agente antineoplásico usado em lesões malignas. A ototoxicidade da cisplatina é geralmente bilateral, irreversível e progressiva. A genisteína é um fitoestrógeno. A genisteína funciona como antioxidante e inibidor do ciclo celular ao inibir a topoisomerase do DNA. A genisteína apresentou efeitos positivos sobre a ototoxicidade com seu efeito antioxidante. Objetivo A cisplatina é um agente antineoplásico usado em adultos e crianças para o tratamento de diversas lesões malignas. Pode causar ototoxicidade irreversível. A genisteína é um fitoestrógeno que funciona como antioxidante e inibidor do ciclo celular ao inibir as enzimas DNA topoisomerase e tirosina-quinase. O efeito protetor da genisteína na prevenção da ototoxicidade induzida pela cisplatina e os níveis de estresse oxidativo foram investigados. Método Trinta e dois ratos Sprague Dawley foram usados em 4 grupos (controle, cisplatina, cisplatina + genisteína, genisteína). As medidas das emissões otoacústicas por produto de distorção foram tomadas nos dias 1, 2 e 5 do protocolo do teste. Foram medidos os níveis séricos de malondialdeído, superóxido dismutase, catalase, glutationa peroxidase, estado antioxidante total, estado oxidante total e índice de estresse oxidativo. Resultados A audição do grupo cisplatina + genisteína foi melhor do que a do grupo cisplatina. Enquanto os parâmetros malondialdeído, estado oxidante total e índice de estresse oxidativo diminuíram significantemente no grupo cisplatina + genisteína em comparação com o grupo cisplatina, o superóxido dismutase mostrou aumento significantemente (p < 0,05). Conclusão A genisteína apresentou efeitos positivos contra a ototoxicidade com seu efeito antioxidante. Nível de evidência Nível 3.

The use of wire cerclage after sternal closure is the standard method because of its rigidity and strength. Despite this, they have many disadvantages such as tissue trauma, operatorinduced failures, and the risk of infection. To avoid complications during sternotomy and promote tissue regeneration, tissue adhesives should be used in post-surgical treatment. Here, we report a highly biocompatible, biomimetic, biodegradable, antibacterial, and UV-curable polyurethane-acrylate (PU-A) tissue adhesive for sternal closure as a supportive to wire cerclage. In the study, PU-As were synthesized with variable biocompatible monomers, such as silk sericin, polyethylene glycol, dopamine, and an aliphatic isocyanate 4,4'-methylenebis(cyclohexyl isocyanate). The highest adhesion strength was found to be 4322 kPa, and the ex vivo compressive test result was determined as 715 kPa. The adhesive was determined to be highly biocompatible (on L929 cells), biodegradable, and antibacterial (on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus bacteria). Finally, after opening the sternum of rats, the adhesive was applied to bond the bones and cured with UV for 5 min. According to the results, there was no visible inflammation in the adhesive groups, while some animals had high inflammation in the cyanoacrylate and wire cerclage groups. These results indicate that the adhesive may be suitable for sternal fixation by preventing the disadvantages of the steel wires and promoting tissue healing. Scientific and Technological Research Council of Turkey [116Z501]; Inonu University Research Fund [IUBAP FDP-2018-1284] ? ACKNOWLEDGMENTS This work was supported financially by the Scientific and Technological Research Council of Turkey (Project no. 116Z501) and Inonu University Research Fund (IUBAP FDP-2018-1284) . The authors acknowledge Prof. Dr. Mehmet Fethi CEYLAN for his assistance in sternal closure surgery.

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.

Objective(s): Varenicline is a selective partial agonist for the nicotinic acetylcholine receptor a4b2 subtype, which is widely used to treat smoking addiction. However, there is still no data about its potential toxic effects on tissues. In this study, we aimed to determine the varenicline-induced toxicity on reproductive and renal tissues in rats. Materials and Methods: Rats were randomly divided into two groups: control (n=10) and varenicline (n=24). Then, rats in each group were sub-divided equally as acute and chronic groups. The control rats were orally given distilled water only. Varenicline was administrated orally as follows: 1st–3rd days 9 µg/kg/day, 4th–7th days 9 µg/kg twice daily, and 8th–90th days 18 µg/kg twice daily. The rats of acute and chronic groups were sacrificed on the 45th and 90th days, respectively. Some tissue markers related to oxidative stress were measured, and sperm characteristics were observed. Results: In the acute group, varenicline led to a significant decrease in SOD activities in both kidney and testis tissues. In the chronic group, varenicline significantly increased MDA and MPO production, and reduced CAT and GPx levels in the kidneys and testes. Also, SOD and GSH levels significantly decreased in the testes. Moreover, sperm characteristics were negatively affected; histopathological deformation was observed in the testes and kidneys in all groups. Conclusion: This study showed that varenicline could detrimentally affect the kidneys and testes in both acute and chronic term usage. Further studies will provide more insights into the molecular dynamics of this damage.

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