Objective: We designed an experimental model of sepsis in rats to investigate the effects of agomelatine (AGO) on lung tissues using molecular and histopathological methods. Materials and Methods: In our experimental model, the 32 rats were divided into 4 groups: group 1: control group (HEALTHY); group 2: lipopolysaccharide group (LPS); group 3: LPS plus 50 mg/kg AGO group (LPS + AGO50); and group 4: LPS plus 100 mg/kg AGO group (LPS + AGO100). An LPS-induced sepsis model was performed to replicate the pathology of sepsis. Rats from all 4 groups were killed after 12 hours, and their lungs were quickly collected. To investigate the therapeutic strategy, we evaluated tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB) messenger RNA expressions by real-time polymerase chain reaction using molecular methods and lung tissue damage indicators using histopathological methods. Results: The expressions of TNF-α and NF-κB were reduced in the groups treated with AGO. The histopathology results supported the molecular results. Conclusion: In this experimental study, we demonstrated for the first time the positive effects of AGO on LPS-induced sepsis in lung tissue using molecular and histopathological methods, indicating that it contributes to the prevention of lung damage. Cite this article as: Köse D, Yüksel TN, Halıcı Z, Çadırcı E, Gürbüz MA. The Effects of Agomelatine Treatment on Lipopolysaccharide-Induced Septic Lung Injuries in Rats. Eurasian J Med 2021; 53(2): 127-31.

Objective(s): Ovarian ischemia/reperfusion (I/R) is an extremely complex pathological problem that begins with oxygen deprivation, progresses to excessive free radical production, and intensifies inflammation. The JAK2/STAT3 signaling pathway is a multipurpose signaling transcript channel that plays a role in several biological functions. Trimetazidine (TMZ) is a cellular anti-ischemic agent. This study aims to investigate the effects of TMZ on ovarian I/R injury in rats. Materials and Methods: sixty four rats were divided into 8 groups at random: healthy(group1); healthy+TMZ20(group2); ischemia (I) (group 3); I+TMZ10(group4); I+ TMZ20(group5); I/R(group6); I/R+TMZ10(group7); I/R+TMZ20(group8). Vascular clamps were placed just beneath the ovaries and over the uterine horns for 3 hr to induce ischemia. The clamps were removed for the reperfusion groups, and the rats were reperfused with care to ensure that the blood flowed into the ovaries, subjecting them to reperfusion for 3 hr. TMZ was administered orally by gavage 6 and 1 hr before operations. At the end of the experiment, ovarian tissues were removed for biochemical, molecular, and histopathological investigation. Results: TMZ administration ameliorated ischemia/reperfusion-induced disturbances in GSH and MDA levels. TMZ treatment inhibited I/R-induced JAK2/STAT3 signaling pathway activation in ovarian tissues. TMZ administration also improved the increase in the mRNA expressions of IL1 beta, TNF-alpha, and NF-KB caused by ischemia/reperfusion injury. Moreover, TMZ treatment improved histopathologic injury in ovarian tissues caused by ischemia/reperfusion. Conclusion: TMZ treatment protected rats against ovarian ischemia/reperfusion injury by alleviating oxidative stress and inflammatory cascades. These findings may provide a mechanistic basis for using TMZ to treat ovarian ischemia-reperfusion injury.

Background and Purpose: The aim of this study is to examine the migration, wound healing, colony formation and cytotoxic effects of reynotrin, quercetin derivative, in breast cancer cells. Methods: In our study, CRL-4010, MCF7 and MDA-MB-231 cells were used to evaluate the different effects of reynoutrin on breast cancer. The IC50 concentration (400 µg/ml) of reynotrin, quercetin and cisplatin in the cells was determined. For cytotoxicity assessments, varying concentrations of quercetin, reynoutrin and cisplatin were applied and incubated 24h and 48h. In addition, to examine its effects on migration, cells were seeded in 6-well plates and incubated for 24 hours. Morever, to assess colony formation, test cells were seeded in 12-well plates at a concentration of 1000 cells/well and incubated overnight. Results: These results indicated that Reynoutrin markedly inhibit the cell viability in breast cancer. Conclusion: We firstly revealed that Reynoutrin suppressed the progression of breast cancer induction and may provide a potential therapeutic target for breast cancer treatment. More detailed studies are needed to show this effect of reynoutrin.

Objective(s): Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. Materials and Methods: 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 pg/kg lipopolysaccharide (LPS), SC), DEX group (200 pg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 pg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 pg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 pg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 pg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hour. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of Tumor Necrosis Factor-alpha (TNF-alpha), vascular endothelial growth factor(VEGF), and Caspase 3 and Caspase 9 mRNA expression), biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Results: Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-alpha, VEGF, Caspase 9, and Caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Conclusion: Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.

Valproic acid (VPA) is among the most commonly used antiepileptic drugs in childhood and adult epilepsy. Although VPA is well tolerated, it can cause life-threatening side effects. VPA has toxic and genotoxic effects. Antioxidants can reverse drugs' toxic and genotoxic effects. Therefore, our study aimed to evaluate the antigenotoxic protective effect of quercetin (QUE) against VPA genotoxicity by in vitro comet assay analysis method. Comet assay analysis was performed in five different groups. Group I; negative control (Sterile H2O), Group II; positive control (H2O2), Group III; VPA was applied in four different dose ranges, Group IV; QUE was applied in four different dose ranges, Group V; For the simultaneous combined administration of VPA and QUE, three different doses of VPA + four different doses of QUE were administered. Low-dose administration of QUE was more effective in ameliorating the damage caused by low-dose VPA (62.5 μg/ml) administration. It is seen that the genotoxic damage caused by the application of 125 μg/ml VPA can be eliminated by QUE at all doses. It was determined that different doses of QUE exhibited a significant antigenotoxic effect against damage caused by 125 µg/mL VPA (P<0.05). In our study, the curative effect of QUE on DNA damage was determined by in vitro comet analysis. Our analysis results showed that QUE ameliorates VPA-induced genetic damage.