Search

Background: The effect of a specific protein kinase A inhibitor H89 on Aquaporin 5 (AQ5) levels, which has a role in the inflammation of asthma pathogenesis, was investigated in this study. Objective: To prove that H89, which was thought to be a promising agent, may show antiinflammatory activity in the treatment of asthma by causing inhibition of the protein kinase A enzyme that is involved in inflammation. Methods: Thirty-two Wistar-Albino adult male rats, ranging between 250 and 350 g, were divided into four groups: (a) control group; (b) sham group, administration of 1 ml ovalbumin (OVA) solution intraperitonal (IP) and 0.1 ml OVA dissolved in dimethyl sulfoxide intranasally; (c) asthma group, IP + intranasally OVA administration; and (d) H89 group, (IP + intranasally OVA) + 0.1 ml H89. The lungs of the rats were evaluated histopathologically and immunohistochemically at the end of the study. Results: The histopathological changes and AQ5 levels of the sham and asthma groups were not statistically different (p > 0.05). However, the parameters were found to be increased in the asthma group compared with the control group (p < 0.001). The alveolar degeneration and vascular congestion were statistically significantly decreased in the H89 group (p < 0.05). The AQ5 levels were reduced in the H89 group, but the difference was not statistically significant. Conclusion: Aquaporin 5 levels and histopathological changes were increased in asthmatic patients, and an improvement was detected with H89 treatment. H89 has an effect on the inflammation of asthma pathogenesis, so it can be thought to be used in asthma treatment. However, more studies are needed to find out the therapy duration and ideal doses of H89 treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible ameliorating effects of agomelatine (AGO) on lipopolysaccharide (LPS)-induced endothelial and cardiac damage. Twenty-four female Wistar Albino rats divided into 3 groups as follows: Control, LPS and LPS + AGO. Total oxidant status (TOS), total antioxidant status (TAS), nuclear factor kappa beta (NF-kβ)/p65, p-NF-kβ, full caspase-8 (Cas-8) and cleaved cas-8 levels were measured in cardiac tissues and creatine kinase MB (CKMB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels in blood biochemically. In addition; cas-8, sirtuin-1 (SIRT-1), interleukin-4 (IL-4), interleukin-10 (IL-10), haptoglobin measured histopathologically in cardiac and aortic tissues. The levels of CKMB, AST, LDH and TOS were increased and TAS were decreased in the LPS group. In Western blot analyses NF-kβ/p65, p-NF-kβ/p65, full and cleaved cas-8 protein levels increased in cardiac tissues of LPS group. In histopathological and immunohistochemical evaluation of the heart sections; hyperemia, micro-hemorrhages and inflammatory cell infiltrations, increase of cas-8, haptoglobin, IL-4 and IL-10 and decrease of SIRT-1 levels were observed in cardiac and endothelial tissues of LPS groups. AGO treatment reversed all these parameters. It was shown that LPS-induced inflammation, oxidative stress and apoptosis via increasing of NF-kβ/p65 signaling, decreasing of SIRT-1 levels and increase of cas-8 levels in heart and endothelial tissues respectively. AGO corrected all these parameters by its antioxidant, antiinflammatory and antiapoptotic activities. [ABSTRACT FROM AUTHOR]

We investigated the antioxidant, anti-inflammatory and anti-apoptotic effects of pregabalin (PREG) on lipopolysaccharide (LPS) induced sepsis related cardiotoxicity via NF-kβ pathways. We used 24 female Wistar albino rats divided into three groups: control, LPS treated and LPS + PREG treated. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-kβ)/p65, p-NF-kβ/p65, caspase-3 (Cas-3) and cleaved Cas-3 were measured in cardiac tissues and creatine kinase MB (CKMB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels were measured in blood samples. Also, Cas-3, granulocyte-colony stimulating factors (G-CSF), interleukin-6 (IL-6), serum amyloid A (SAA) and inducible nitric oxide synthase (iNOS) were measured immunohistochemically in heart and aorta tissue. In the LPS group; the levels of CKMB, AST, LDH, TOS, OSI increased and TAS decreased. TNF-α, p-NF-kβ/p65 and Cas-3 protein levels also increased in the LPS group. Immunohistochemical evaluation of the heart and aorta revealed a significant increase in the levels of Cas-3, G-CSF, SAA, IL-6 and iNOS in the LPS group. PREG treatment restored all measurements to near normal. LPS induced cardiovascular toxicity was due to inflammation, oxidative stress and apoptosis. PREG ameliorated the damage by inhibition of NF-kβ phosphorylation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of α-lipoic acid (α-LA) on oxidative damage and inflammation that occur in endothelium of aorta and heart while constant consumption of high-fructose corn syrup (HFCS). The rats were randomly divided into three groups with each group containing eight rats. The groups include HFCS, HFCS + α-LA treatment, and control. HFCS was given to the rats at a ratio of 30% of F30 corn syrup in drinking water for 10 weeks. α-LA treatment was given to the rats at a dose of 100 mg/kg/day orally for the last 6 weeks. At the end of the experiment, the rats were killed by cervical dislocation. The blood samples were collected for biochemical studies, and the aortic and cardiac tissues were collected for evaluation of oxidant–antioxidant system, tissue bath, and pathological examination. HFCS had increased the levels of malondialdehyde, creatine kinase MB, lactate dehydrogenase, and uric acid and showed significant structural changes in the heart of the rats by histopathology. Those changes were improved by α-LA treatment as it was found in this treatment group. Immunohistochemical expressions of tumor necrosis factor α and inducible nitric oxide synthase were increased in HFCS group, and these receptor levels were decreased by α-LA treatment. All the tissue bath studies supported these findings. Chronic consumption of HFCS caused several problems like cardiac and endothelial injury of aorta by hyperuricemia and induced oxidative stress and inflammation. α-LA treatment reduced uric acid levels, oxidative stress, and corrected vascular responses. α-LA can be added to cardiac drugs due to its cardiovascular protective effects against the cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Pituitary apoplexy (PA) is a life-threatening clinical syndrome. Dopamine receptor agonists are the drugs of choice in the treatment of prolactinomas. The use of cabergoline is reported to cause an increased risk of PA, particularly in macroprolactinomas of cystic nature. In this report, we present a patient with a cystic macroprolactinoma who developed PA on the 16th week of cabergoline treatment. [ABSTRACT FROM AUTHOR]

Natural compounds include complex chemical compounds that exist in plants, animals and microbes. Due to their broad spectrum of pharmacological and biochemical actions, they have been widely used to treat multifactorial diseases, including cancer. In addition, their demonstrated neuroprotective properties strongly support their use in the treatment of neurological diseases. The present study investigated the effect of cannabidiol (CBD), which can easily cross the placental barrier and is known to have anti-inflammatory effects, on fetal neuroinflammation and neurogenesis in a systemic inflammation model during pregnancy. Herein, 12 weeks adult pregnant rats (n = 30) were randomly divided into 5 groups with 6 rats in each group as follows: Control, LPS (lipopolysaccharide, i.p.), LPS+CBD 5 mg/kg (i.p.), LPS+CBD10 mg/kg (i.p.) and LPS+CBD30 mg/kg (i.p.). After the injections, blood samples of rats were collected, fetuses and placentas were taken by hysterectomy. Histopathological analysis, immunohistochemical staining, ELISA and immunoblotting analysis were performed to investigate neuroinflammatory and neurogenesis parameters in fetal brain and placenta tissues. Our findings indicated that CBD administration importantly suppressed the inflammatory process in the rat fetal brain by decreasing interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and diminishing nuclear factor kappa B (NF-κB) activation. Moreover, CBD inhibited lipopolysaccharide (LPS)-induced increasing levels of neuroinflammation-associated proteins, including glial fibrillary acidic protein (GFAP), S100B and cAMP-response element binding protein (CREB). These results suggest that CBD usage in pregnancy with inflammation conditions may be an effective therapeutic option for preventing conditions that may cause neuroinflammation in the fetal brain and adversely affect neurogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Methotrexate (MTX), a widely used chemotherapeutic agent, often induces hepatotoxicity, limiting its clinical utility. Cannabidiol (CBD), derived from hemp, possesses antioxidant, anti-inflammatory, and antiapoptotic properties. This study aims to investigate CBD's protective effects against MTX-induced liver injury and elucidate the underlying mechanisms. Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (20 mg/kg intraperitoneally [i.p.] once), MTX+CBD (20 mg/kg i.p. once + 5 mg/kg i.p. for seven days), and CBD (5 mg/kg, i.p. for seven days). Biochemical analyses of serum and liver tissues were performed to assess oxidative stress markers (total oxidant status, total antioxidant status, oxidative stress index), liver function tests (AST, ALT), and antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase). Histopathological and immunohistochemical examinations were conducted to evaluate liver tissue damage and TNF-α expression. Genetic analyses were performed to measure the expression levels of SIRT-1, p53, Bcl-2, and Bax genes using RT-qPCR. MTX administration increased oxidative stress markers, liver enzymes, TNF-α, p53, and Bax levels while decreasing antioxidant defenses and SIRT-1 expression. CBD administration reversed these alterations effectively. CBD mitigated MTX-induced hepatotoxicity by reducing oxidative stress, inflammation, and apoptosis. It activates antioxidant defenses via SIRT-1 upregulation, suppresses inflammation by reducing TNF-α, and prevents apoptosis by modulating p53, Bcl-2, and Bax gene expressions. These findings suggest CBD could be a promising therapeutic agent for chemotherapy-induced liver damage. Further research is warranted to explore additional pathways and broader molecular mechanisms.

Chorioamnionitis is closely associated with preterm labor and poses a significant public health concern. In this pathological process where inflammation plays a key role, intracellular mechanisms such as endoplasmic reticulum stress are crucial. In this study, we aimed to explore the potential positive outcomes of the combined use of salubrinal (SLB) with magnesium (Mg) treatment in chorioamnionitis. Thirty pregnant rats were divided into 5 groups as: Control, LPS (1 mg/kg), LPS + SLB (1 mg/kg), LPS + Mg (Dhaka protocol), LPS + SLB + Mg. Rats were sacrificed 4 h after LPS administration, then placental and fetal brain tissues were collected. LPS administration enhanced the levels of tumor necrosis factor-alpha, vascular endothelial growth factor, caspase-3 immunoexpressions, BAX, eukaryotic initiation factor 2-alpha, s100, and glial fibrillary acidic protein expressions and lowered BCL2 expressions in the placenta or fetal brains. SLB and Mg treatments were observed to reverse all these findings, and the most significant positive effect was in the LPS + SLB + Mg group. The known anti-inflammatory activity of Mg, when used with SLB, preventing the transition to apoptosis and increasing antioxidant enzyme activity, as identified in this study, can contribute significantly to the literature. However, these results need to be supported by additional molecular studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Halil Asci reports financial support was provided by Scientific and Technological Research Council of Turkey and Scientific Research Projects Coordination Unit of Suleyman Demirel University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been suggested to possess anti-inflammatory properties in diabetes. The aim of this study is to evaluate the role of DPG administration in preventing lipopolysaccharide (LPS)-induced damage in the female genital system. Thirty-two female Wistar Albino rats were randomly allocated into four groups: control group, LPS group, LPS + DPG group and DPG group. At the end of the experimental phase, ovary, fallopian tube and uterus tissues were collected for histopathological, immunohistochemical, genetic and biochemical analyses. The findings showed that LPS caused histopathological changes characterized by marked hyperaemia, mild to moderate haemorrhage, oedema and neutrophil leucocyte infiltrations and degenerative and necrotic changes in the female genital tract. In addition, it decreased total antioxidant status (TAS), increased total oxidant status (TOS) and oxidative stress index (OSI) levels. LPS also increased the expressions of Cas-3, G-CSF and IL-1β in the ovary, fallopian tubes and uterus immunohistochemically. While Claudin-1 expression decreased, NLRP3 and AQP4 gene expressions increased due to LPS. However, DPG treatment prevented all these changes. The results of this study indicate that, DPG can be used to prevent LPS-induced lesions in the female reproductive system., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 inhibitor and is used in the treatment of diabetes. In this study, we aimed to investigate the effect of DPG on cardiotoxicity caused by systemic inflammation via endoplasmic reticulum (ER) stress and autophagy., Methods and Results: Four groups of thirty-two Wistar Albino rats were created: Control (1 ml oral physiological saline for five days and intraperitoneal saline on the 5th day), LPS (1 ml oral physiological saline for five days and intraperitoneal 5 mg/kg of LPS on the 5th day), LPS + DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of LPS intraperitoneally on the 5th day), and DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of SF intraperitoneally on the 5th day). Histopathological and immunohistochemical analyses were performed on heart and aorta tissues. ER stress and autophagy gene markers in heart tissues were evaluated by RT-qPCR. Oxidative stress in heart tissues and serum cardiac enzymes were analyzed by spectrophotometric method. The heart and aortic tissues of the LPS group showed increased expressions of Tumor Necrosis Factor-α (TNF-α) and Caspase-3 (Cas-3), along with mild hyperemia, slight inflammatory cell infiltrations, and myocardial cell damage. The heart tissues also showed genetically increased expressions of include binding immunoglobulin protein (BiP/ GRP78), protein kinase RNA-like ER Kinase (PERK), inositol-requiring enzyme 1 (IRE-1), activating transcription factors 4 (ATF-4), activating transcription factors 4 (ATF6), C/EBP homologous protein (CHOP), and BECLIN 1. Furthermore, Creatine kinase-MB (CK-MB) and Lactate dehydrogenase (LDH) levels in blood tissue significantly increased, according to biochemical analysis. With DPG therapy, all of these findings were reversed., Conclusion: In conclusion, DPG protects against the cardiotoxic effect of systemic inflammation with its antioxidant and anti-inflammatory properties by regulating ER stress and autophagy pathways., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI., Methods: Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 min of ischemia followed by 30 min of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses., Results: Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols., Conclusion: In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.

Background: The adverse effects of radiotherapy (RT) primarily occur through oxidative stress, and attempts are being made to mitigate these effects. L-Carnitine (L-Car) involved in physiological functions, possesses antioxidant and tissue-protective properties. The goal of this investigation is to appraise the radioprotective efficacy of L-Car supplementation., Methods and Results: The groups were established by dividing thirty-two rats as: control, RT (10 Gy), RT + L-Car (200 mg/kg/d), L-Car. Upon completion of the experiment, the livers were harvested for histopathological, immunostaining [tumor necrosis factor-alpha (TNF-α), Caspase-3], spectrophotometric [total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI)], and mRNA expression [(Nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1), Heme Oxygenase (HO-1), Transforming growth factor beta 1 (TGF-β1)] analyses. In the damage group, decreased Keap-1, Nrf2, HO-1, and TAS values, along with increased histopathological findings, alanine transferase, aspartate transferase, TNF-α, Caspase-3, TOS, OSI, TGF-β1 levels were found. All findings were improved with L-Car treatment., Conclusions: Considering these findings, it can be inferred that L-Car exhibits tissue-protective effects against organ damage predominantly induced by RT-related oxidative stress. Additionally, it has prevented the development of inflammation, apoptosis, and fibrosis. Therefore, L-Car may be considered as a supplement to reduce complications associated with RT., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Sepsis-induced renal damage poses a significant threat, necessitating effective therapeutic strategies. Cannabidiol (CBD) has beneficial effects on tissues and their functions by exhibiting antioxidant and anti-inflammatory effects. This study investigates the potential protective effects of CBD in mitigating lipopolysaccharide (LPS)-induced renal injury in Wistar Albino rats. Thirty-two Wistar Albino rats were categorized into control, LPS (5 mg/kg i.p.), LPS + CBD, and CBD (5 mg/kg i.p.) groups. After the experiment, samples were collected for biochemical, genetic, histopathological, and immunohistochemical analyses. Oxidative stress markers as total oxidant status (TOS) and total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), immune staining as tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), caspase-3, gene expressions as nuclear factor erythroid 2-related factor 2 (NRF2), C/EBP homologous protein (CHOP), caspase-9, glucose-regulating protein 78 (GRP78), B-cell leukemia/lymphoma 2 (Bcl2), and tissue histology have been examined. The LPS-exposed group exhibited significant renal abnormalities, mitigated by CBD intervention in the LPS + CBD group. CBD reduced immunoexpression scores for TNF-α, caspase-3, and IL-10. Biochemically, CBD induced a positive shift in the oxidative balance, increasing TAS, SOD, and GPx, while decreasing TOS, OSI, and MDA levels. Genetic analyses highlighted CBD's regulatory impact on NRF2, CHOP, caspase-9, GRP78, and Bcl2, providing molecular insights into its protective role against LPS-induced renal damage. This study underscores CBD as a promising protective agent against sepsis-induced renal damage. Our findings could provide valuable insights into potential therapeutic avenues for addressing renal complications in sepsis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to examine the protective role of nebivolol (NEB) on liver tissue against the lipopolysaccharide (LPS)-induced sepsis model in rats by targeting endoplasmic reticulum (ER) stress-related binding immunoglobulin protein (Bip), CCAAT-enhancer-binding protein homologous protein (Chop) signaling pathways. Four groups, each comprising eight rats, were established: control, LPS, LPS + NEB, and NEB. Biochemical analyses included total oxidant status (TOS), serum aspartate transaminase (AST), and alanine aminotransferase (ALT) levels. Additionally, genetic assessments involved Chop and Bip/GRP78 mRNA expression levels, while histopathological examinations were conducted. Immunohistochemistry was used to determine interleukin-1 beta (IL-1 β) and caspase-3 levels. The LPS group exhibited significantly higher AST, ALT, oxidative stress index, and TOS levels compared to the control group. Moreover, the LPS group demonstrated markedly increased Chop and Bip/GRP78 mRNA expression compared to the control group. Immunohistochemical analysis of the LPS group revealed significant upregulation in IL-1β and caspase-3 expressions compared to the control group. Additionally, the LPS group showed significant hyperemia, mild hemorrhage, and inflammatory cell infiltrations. Comparatively, the LPS+NEB group exhibited a reversal of these alterations when compared to the LPS group. Collectively, our findings, suggest that NEB holds promise as a treatment in conditions where oxidative damage, inflammation, and ER stress-related apoptosis play significant roles in the pathogenesis., (© 2024. The Author(s).)

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a condition that can occur primarily in patients undergoing or have previously undergone therapy with bisphosphonates, particularly in the presence of risk factors, such as tooth extraction (TE)., Purpose: This study aimed to evaluate the effect of selenium (SEL) administration on the prevention of osteonecrosis of the jaw in an MRONJ animal model., Study Design, Setting, and Sample: This study was a longitudinal in vivo animal study using a TE model in a sample of 48 Wistar rats., Predictor Variable: The predictor variables were SEL exposure, timing of SEL exposure, and zoledronic acid (ZOL) exposure. The animals were randomly assigned to 4 treatment groups (n = 12 per group): 1) saline (negative control), 2) ZOL (positive control), 3) SEL preop  + ZOL, and 4) ZOL + SEL postop . The animals were administered saline (negative control) or ZOL (0.06 mg/kg, intraperitoneally) once a week for 5 weeks. All rats underwent TE at the end of the fifth week. SEL (0.3 mg/kg, intraperitoneally) was administered once daily for 15 days to the SEL preop  + ZOL group before TE and to the ZOL + SEL postop group after TE. All animals were sacrificed at the end of the ninth week., Main Outcome Variables: The primary outcome variables were new bone area, necrotic bone area, fibrosis, new connective tissue formation, and inflammatory cell infiltration in the histopathological analysis, as well as angiogenesis and percentage of osteoblasts in the immunohistochemical analysis., Covariates: There was none., Analyses: Statistical analysis was conducted using the Kruskal-Wallis test, followed by post hoc Bonferroni-corrected Mann-Whitney U tests, with a significance level of P ≤ .05., Results: The new bone area was higher in the ZOL + SEL postop group (3.00 score) than in the saline group (0.58 ± 1.08 score, P < .001) and the ZOL group (0.82 ± 1.40 score, P = .001), while the necrotic bone area was lower in the ZOL + SEL postop group (0.08 ± 0.29 score) than in the ZOL group (2.82 ± 0.40 score, P < .001) and the SEL preop  + ZOL group (1.67 ± 0.89 score, P = .007). The percentage of osteoblasts was higher in the ZOL + SEL postop group (18.73%) than in the saline group (8.63%, P < .001) and the ZOL group (0.07%, P < .001), and it was also higher in the SEL preop  + ZOL group (18.49%) than in the ZOL group (0.07%, P < .001)., Conclusion and Relevance: In conclusion SEL prevents MRONJ, with postoperative SEL demonstrating greater prevention effects. Given these findings, we hypothesize that SEL exposure may decrease the risk of MRONJ., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Side effects of doxorubicin (DOX) are mainly due to oxidative stress, with the involvement of inflammatory and apoptotic mechanisms. Agomelatine (AGO) is a melatonin receptor agonist with antioxidant, anti-inflammatory, and anti-apoptotic features. This study aimed to evaluate the effects of AGO with different doses on DOX-induced neurotoxicity. Rats were divided into four groups as control, DOX (40 mg/kg, intraperitoneal single dose), DOX + AGO20 (20 mg/kg AGO oral gavage for 14 days), and DOX + AGO40 (40 mg/kg AGO oral gavage for 14 days). On day 14, brain tissues were collected for biochemical, histopathological, and genetic examinations. DOX significantly increased malondialdehyde and decreased superoxide dismutase and catalase (CAT) levels. CAT levels were significantly increased only in the DOX + AGO40 group compared to the DOX group ( p  = 0.040) while other changes in oxidant and antioxidant indicators were insignificant. DOX-induced significant increases in TNF-alpha and NF-κB were reversed following both low and high-dose AGO administration in a dose-dependent manner ( p  < 0.001 for both doses). Cellular shrinkage, pycnotic change, and vacuolization in apoptotic bodies were apparent in the cortical and hippocampal areas of DOX-treated samples. Both doses of AGO alleviated these histopathological changes ( p  = 0.01 for AGO20 and p  = 0.05 for AGO40). Significantly increased apoptosis shown with caspase-3 immunostaining in the DOX group was alleviated following AGO administration, with additional improvement after high-dose treatment ( p  < 0.01 for DOX compared to both AGO groups and p  < 0.05 for AGO40 compared to AGO20). AGO can be protective against DOX-induced neurotoxicity by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms in a dose-dependent manner.

Background: Doxorubicin (DOX) may cause various neurological side effects in the brain. Lercanidipine (LRD) has antioxidant, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the potential benefits of., Methods and Results: Lercanidipine in reducing doxorubicin-induced neuroinflammation and maintaining the expressions of choline acetyltransferase. Thirty-two adult Wistar albino female rats were divided into four groups as Control, DOX (20 mg/kg intraperitoneally), DOX + LRD 0.5 (0.5 mg/kg orally), and DOX + LRD2(2 mg/kg orally). Twenty-four hours after the last drug administration (9th day), brain tissues were taken for histopathological, immunohistochemical (choline acetyltransferase [CHAT], interleukin-10 [IL-10], and caspase-3 [Cas-3] staining), biochemical (total antioxidant status [TAS], total oxidant status [TOS], and oxidative stress index [OSI]), and genetic analyzes (PI3K/AKT/HIF1-α and IL-6 gene expressions). Histopathological analyses revealed hyperemia, slight hemorrhage, degeneration, neuronal loss, gliosis in the cerebellum, and neuronal loss in the brain cortex and hippocampus in the DOX group. According to other analyzes, decreased CHAT, PI3K, AKT, HIF1-α and increased IL-6, IL-10, Cas-3 expression were observed in the DOX group., Conclusions: Both LRD doses reversed all these findings, but LRD2 was observed to be more effective. In conclusion, we determined that LRD has potential therapeutic effect by reducing DOX-induced neuroinflammation, oxidative stress and apoptosis in brain tissues., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: To explore the pathophysiological mechanism of subarachnoid haemorrhage (SAH) using cellular oxidative stress mechanisms and inflammation., Material and Methods: A total of 20 Wistar Albino rats were divided into two groups, namely sham and SAH. On day 0, 0.3 mL of saline in the sham group and 0.3 ml of autologous blood in the SAH group were applied in the cisterna magna of the animals. After sacrification on the 7th day of the procedure, brain, blood and heart tissues were collected. In different tissues, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), creatin kinase MB (CKMB) and lactate dehydrogenase (LDH) levels were detected biochemically. AKT, sirtuin-1 (SIRT-1), NF-E2-related factor 2 (NRF2), heme oxygenase-1 (HO-1) genes and glutathione peroxidase-4 expression were examined genetically. Moreover, histopathological analyses were conducted both in heart and brain tissues., Results: Enhanced TOS, OSI levels in all tissues and glial fibrillary acidic protein (GFAP) expressions in brain tissue and NFkβ, IL-6 and Cox-1 expressions in heart tissues; it was observed that levels of TAS in blood and AKT, SIRT-1, NRF2 and HO-1 gene expressions in brain tissue were decreased., Conclusion: In the oxidative stress and inflammation situation that takes place following SAH, AKT, SIRT-1, NRF2 and HO-1 pathways, which are antioxidant mechanisms, are suppressed and GFAP, NFkβ, IL-6, Cox-1 expressions, which trigger inflammation, are enhanced. Treatment of SAH necessitates studies on the inhibition or activation of such pathways.

Methotrexate (MTX) is an antineoplastic agent and has neurotoxic effects. It exerts its toxic effect on the brain by triggering inflammation and apoptosis. Cannabidiol (CBD) is an agent known for its antioxidant, anti-inflammatory effects in various tissues. The aim of this study is to examine the protective effects of CBD treatment in various brain structures from MTX damage and to evaluate the effect of intracellular pathways involved in apoptosis. Thirty-two adult Wistar Albino female rats were divided into four groups as control, MTX (20 mg/kg intraperitoneally [i.p.]), MTX + CBD (0.1 mL of 5 mg/kg i.p.), and CBD (for 7 days, i.p.). At the end of the experiment, brain tissues collected for biochemical analyses as total oxidant status (TOS), total antioxidant status, oxidative stress index (OSI), histopathological and immunohistochemical analyses as tumor necrosis factor-α (TNF-α), serotonin, mammalian target of rapamycin (mTOR) staining, genetic analyses as caspase-9 (Cas-9), caspase-12 (Cas-12), C/EBP homologous protein (CHOP), and cytochrome-c (Cyt-c) gene expressions. In the histopathological and immunohistochemical evaluation, hyperemia, microhemorrhage, neuronal loss, and significant decreasing expressions of seratonin were observed in the cortex, hippocampus, and cerebellum regions in the MTX group. mTOR, TNF-α, Cas-9, Cas-12, CHOP, and Cyt-c expressions with TOS and OSI levels were increased in the cortex. It was observed that these findings were reversed after CBD application in all regions. MTX triggers neuronal apoptosis via endoplasmic reticulum and mitochondrial stress while destroying serotonergic neurons. The reversal of the pathological changes with CBD treatment proves that it has anti-inflammatory and antiapoptotic activity in brain., (© 2023 Wiley Periodicals LLC.)

Background: The blood supply of the tissue is very important in the acceleration of wound healing. Radiofrequency electromagnetic field (RF) and the pulsed magnetic field (PMF) increase vasodilation to contribute wound healing. The aim of this study was to evaluate the effects of RF and PMF on wound healing via hypoxia-inducible factor-1 alpha (Hif-1α)/endothelial nitric oxide synthase (eNOS) pathway., Methods: Forty-eight rats were divided into 4 groups as sham (wound created only), PMF (27.12 MHz, 12 times a day at 30-min intervals), RF (0.5 mT, continuously) and PMF + RF groups. Wounds were created at 1.5 × 1.5 cm size to the dorsal region, and animals were put into unit. Six animals were killed on days 4 and 7; wound tissues were collected for histopathological, immunohistochemical as collagen-4, cytokeratin, matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) staining and Hif-1α/eNOS/VEGF expressions., Results: On day 4, in addition to increasing VEGF and MMP-9 stainings, connection between intact tissue and scar tissue which was stronger in the RF- and PMF-applied groups was observed. On day 7, epithelization started; inflammatory reaction decreased; collagen production, cytokeratin, VEGF and MMP-9 expression enhanced, especially in the RF + PMF applied group. eNOS, Hif-1α and VEGF expression levels were found to be significantly highest in both days of RF + PMF-applied group., Conclusions: This study revealed that both in vitro RF and PMF applications can cause notable changes in factors that are required for tissue repair on wound healing such as epithelization, connective tissue formation, collagen production and angiogenesis via vasodilatory Hif-1α/eNOS pathway and VEGF signaling., No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background and Objectives: Ocular alkaline burn is a clinical emergency that can cause permanent vision loss due to limbal stem cell deficiency and corneal neovascularization (CNV). Although the basic pathogenetic mechanisms are considered to be acute oxidative stress and corneal neovascularization triggered by inflammation, the underlying intracellular mechanisms have not been clearly elucidated. The aim of this study was to investigate the role of endoplasmic reticulum (ER) stress on inflammation and neovascularization, and the effect of the ER stress inhibitor salubrinal (SLB), as a novel treatment in a corneal alkaline burn model in rats. Methods: Chemical burns were created by cautery for 4 s using a rod coated with 75% silver nitrate and 25% potassium nitrate in the corneal center for the corneal neovascularization (CNV) model. Twenty-eight Wistar albino rats were divided into four groups: SHAM, CNV, CNV + SLB, and CNV + bevacizumab (BVC). After the CNV model was applied to the right eye, a single subconjunctival dose (0.05 mL) of 1 mg/kg salubrinal was injected into both eyes in the CNV + SLB group. A total of 1.25 mg/mL of subconjunctival BVC was administered to the CNV + BVC group. Fourteen days after experimental modeling and drug administration, half of the globes were placed in liquid nitrogen and stored at -20 °C until biochemical analysis. The remaining tissues were collected and fixed in 10% buffered formalin for histopathological and immunohistochemical analysis. Three qualitative agents from three different pathways were chosen: TNFR for inflammation, endothelial nitric oxide synthase (e-NOS) for vascular endothelial growth factor (VEGF)-mediated vascular permeability, and caspase-3 for cellular apoptosis. Results: Significantly lower caspase-3 and eNOS levels were detected in the CNV + SLB and CNV + BVC groups than in the CNV group. Additionally, histopathological evaluation revealed a significant decrease in neovascularization, inflammatory cell infiltration, and fibroblast activity in the CNV + SLB and CNV + BVC groups. The endoplasmic reticulum stress inhibitor, salubrinal, administered to the treatment group, attenuated apoptosis (caspase-3) and inflammation (e-NOS). In the control group (left eyes of the SLB group), salubrinal did not have a toxic effect on the healthy corneas. Conclusion: The ER stress pathway plays an important role in angiogenesis after alkaline corneal burns, and treatment with SLB modulates this pathway, reducing caspase-3 and eNOS levels. Further studies are needed to understand the molecular mechanisms altered by SLB-mediated therapy. The fact that more than one mechanism plays a role in the pathogenesis of CNV may require the use of more than one molecule in treatment. SLB has the potential to affect multiple steps in CNV pathogenesis, both in terms of reducing ER stress and regulating cellular homeostasis by inhibiting the core event of integrated stress response (ISR). Therefore, it can be used as a new treatment option and as a strengthening agent for existing treatments. Although blockade of intracellular organelle stress pathways has shown promising results in experimental studies, more in-depth research is needed before it can be used in routine practice. To the best of our knowledge, this study is the first to report the role of ER stress in corneal injury.

Background: Systemic inflammatory response could affect many systems. Cardiac dysfunction develops due to cardiovascular system damage and could be mortal. Selenium is a trace element that can be used as a dietary supplement and has antioxidant, anti-inflammatory, and anti-apoptotic properties. This study aims to evaluate the protective effects of selenium on cardiovascular damage via silenced information regulator 1 (SIRT1)/p53 and cytochrome C (Cyt-c)/ caspase-3 (Cas-3) pathways., Methods and Results: Thirty-two rats were randomly divided into 4 groups as control, LPS (0.1 mg/kg, intraperitoneally(i.p.), 2-7 days) and LPS + Selenium (LPS-0.1 mg/kg, i.p., 2-7 days, selenium - 100 µg/kg, i.p., 1-7 days) and selenium (100 µg/kg, i.p., 1-7 days) group. On the 8th day of the experiment, rats were sacrificed. Blood samples and half of the left ventricles were collected for biochemical and genetic analysis. The remaining left ventricles and aorta were taken for histological and immunohistochemical analysis. In the LPS group myocardial hemorrhages, hyperemia, and endothelial cell loss were observed. Also, Cas-3 and vascular endothelial growth factor (VEGF) expressions; creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), ischemia modified albumin (IMA), total oxidant status (TOS), oxidative stress index (OSI) levels; p53, Cyt-c, Cas-3 mRNA expressions increased while total antioxidant status (TAS) levels, glutathione peroxidase (GPx) activity, SIRT1 mRNA expression decreased. Selenium treatment reversed all these changes., Conclusion: Selenium showed protective effects on cardiovascular injury via regulating SIRT1/p53 and Cyt-c/Cas-3 pathways. This study enlightened the possible usage of selenium on cardiotoxicity., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Ramelteon (RML) is a potent, selective agonist of the high-affinity melatonin receptor 1 and 2 receptors. In addition, RML is known to have antioxidant and anti-inflammatory effects. In this study, we aimed to investigate the effects of RML on HIF-1α, VEGF and e-NOS signaling pathway in a rat model of endotoxin-induced uveitis (EIU)., Methods: Twenty-eight Wistar albino rats were divided into 4 groups as controls, lypopolysaccharide (LPS) group (5 mg/kg i.p.), LPS  +  RML group (5 mg/kg i.p and 8 mg/kg orally, respectively) and RML group (8 mg/kg orally). EIU was induced by a single intraperitoneal LPS injection. Histopathological and genetical analyses were performed., Results: In histopathological analysis, LPS caused mild anterior uveitis characterized by increased surface area of iris leaflets and ciliary body due to edema, mild to moderate congestion, and inflammatory infiltrate 6 h following the injection. The pathological findings were reduced by RML. Higher inflammation levels seen in LPS group were significantly reduced in LPS  +  RML group. Also, HIF-1 α, eNOS and VEGF expressions increased in LPS and decreased in LPS  +  RML group., Conclusion: RML treatment reversed the changes in the HIF-1α /eNOS/ VEGF signaling pathway in LPS-induced uveitis in rats, preventing the progression of the damage and showed positive effects.

Despite the wide clinical indications, methotrexate (MTX) use is limited because of serious side effects including liver toxicity. MTX was shown to cause tissue damage by mainly oxidative stress and also inflammation and apoptosis. Thus, Nebivolol (NEB) which has antioxidant and antiapoptotic properties were thought to be effective against MTX-induced injury. This study aimed to evaluate the effects of NEB on MTX-induced liver toxicity via AKT/Hypoxia-Inducible Factor 1 Alpha (HIF1α)/Endothelial Nitric Oxide Synthase (eNOS) signaling pathways. Rats were divided into three groups as control, MTX, and NEB. A single dose of MTX (20 mg/kg intraperitoneally) was given to the rats on the first day of the experiment and NEB (10 mg/kg, daily by oral gavage) was given to the treatment group for a week. At the end of the experiment, bloods were taken for aspartate transaminase (AST), alanine aminotransferase (ALT), and total bilirubin (T-BIL) analyses. Liver tissues were harvested for biochemical (total oxidant status (TOS) and total antioxidant status (TAS), genetic (PCR analyses for AKT1, eNOS, and HIF1a), and histological (Hemotoxylin-Eosin, Masson Trichome, Periodic Acid Schiff-Asien Blue, reticulin for histological, and CD3 for immunohistochemical staining) analyses. MTX increased the levels of TOS values, AST, ALT, T-BIL levels and decreased the expressions of AKT/HIF1α/eNOS. NEB treatment reversed all these changes markedly via decreasing inflammation by nitric oxid (NO) production. In conclusion, NEB treatment significantly preserves the liver by decreasing oxidant levels and inflammatory parameters through HIF1α/eNOS signaling. Due to the antioxidant properties of NEB, it can be used in other liver injury models sharing the same pathway.

Background We compared the neuroprotective effects of Fingolimod (fng), a neuroprotective and anti-inflammatory drug, with that of magnesium sulfate (MgSO4), alone and in combination, in fetal rat whose mothers were exposed to endotoxin. Method Seven groups of pregnant rats (28 total) were evaluated at 0.8 gestation - Group1 - saline only; 2 - endotoxin only; 3 - endotoxin + MgSO4; 4 - endotoxin + fng; 5 - endotoxin + MgSO4 + fng; 6 - saline + fng; 7 - saline + MgSO4 + fng. Preterm labor was induced 4 h after intraperitoneal endotoxin administration. Fetal brain samples were examined immunohistochemically using S100β, IL-6, and IL-10. Results Endotoxin caused increased expression of S100β, IL-6, and IL-10. Compared with MgSO4 alone, combined treatment was associated with lower expression of IL-10, IL-6 and S100 β. Conclusion Fng decreases inflammatory markers after in-utero exposure to endotoxin, has a synergistic effect combined with MgSO4, and may be a candidate neuroprotective drug for inflammation-induced preterm brain injury.

Background: Neuroinflammation plays an important role in the pathogenesis of many psychiatric and neurodegenerative diseases. Dexpanthenol (Dex) is an alcoholic analogue of pantothenic acid with antioxidant, anti-inflammatory and anti-apoptotic properties. The purpose of this study was to determine the effect of dexpanthenol on lipopolysaccharide (LPS)-induced brain injury, specifically on the CREB/BDNF pathway., Method: Thirty-two rats were distributed into four groups: control, LPS, LPS + Dex and Dex groups. In this study, using real-time PCR, we evaluated changes in the gene expression of BDNF and CREB in the hippocampal brain tissue. Total antioxidant status (TAS), total oxidant status (TOS) were measured spectrophotometrically in the cortical tissue. Brain and cerebellum tissues were collected for histopathological examination and immunohistochemical assessment of tumor necrosis factor alpha (TNF-α) and caspase-3 (Cas-3)., Result and Discussion: In the LPS + Dex group, TAS levels were significantly higher while TOS and OSI levels were significantly lower than the LPS group. In the LPS + Dex and Dex group, BDNF relative mRNA expressions were significantly higher than the LPS group. The levels of CREB relative mRNA expression in LPS and LPS + Dex group were significantly lower than the control group. An increased expression of Cas-3 and TNF-α in the LPS group and a decreased expression in the LPS + Dex group were observed in the immunohistochemical examination., Conclusion: According to these results, it may be considered that CREB-mediated BDNF synthesis may play a role in the etiopathogenesis of neuroinflammation. By regulating these changes with dexpanthenol treatment, a positive contribution may be made to neuroinflammation treatment.

Objective: We investigated the effects of different doses of pregabalin on the pathophysiologic changes in early brain injury after subarachnoid hemorrhage (SAH) in rats., Methods: Thirty-eight Wistar albino rats were divided into 4 groups: control (n = 8), SAH (n = 10), SAH plus 30 mg/kg/day of pregabalin (n = 10), and SAH plus 60 mg/kg/day of pregabalin (n = 10). SAH was induced with 0.3 mL of autologous blood injected to the cisterna magna of rats. Pregabalin was administered intraperitoneally. Oxidative stress markers, mRNA expression of endothelial nitric oxide synthase, hypoxia-inducible factor-1α, and vascular endothelial growth factor, and histopathological changes were evaluated., Results: Pregabalin increased mRNA expression of endothelial nitric oxide synthase, hypoxia-inducible factor-1α, and vascular endothelial growth factor in a dose-dependent manner. Significant improvement in the histopathological parameters was observed at 60 mg/kg, including a decrease in diffuse hemorrhagic areas, edema and apoptotic bodies in the associated cortical area, evident vacuolization in the hippocampal area, and apoptotic bodies. However, these improvements were not observed with the lower dose (30 mg/kg). In contrast, the antioxidant effect was greater with 30 mg/kg of pregabalin than with 60 mg/kg., Conclusions: Although the antioxidant effect was significant with the lower dose of pregabalin, the anti-inflammatory effects via vasodilatation were more marked with the higher dose. Significant improvements in the histopathological changes were observed with the higher dose of pregabalin. The dose-dependent effects of pregabalin on SAH should be evaluated in animal studies as a function of time and in the acute and chronic phases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Fingolimod (FIN) is used for multiple sclerosis treatment and has potential antiapoptotic and anti-inflammatory effects. We aimed at expanding our knowledge on various immunohistochemical markers for elucidating the possible mechanisms of action of fingolimod in the placenta and fetal lung and brain., Methods: Sixteen pregnant rats were divided into four groups. On gestational day 17, lipopolysaccharide (LPS) was injected intraperitoneally to induce preterm fetal injury followed by intraperitoneal injection of fingolimod. Hysterotomy for preterm delivery was performed 6 h after fingolimod was injected. The study groups included (1) control, (2) LPS (1 mg/kg), (3) FIN (4 mg/kg), and (4) FIN + LPS. Fetal brain and lung and placenta samples were collected for histopathological examination. Moreover, fetal lungs (surfactant protein-A (SP-A), SP-B, SP-D, caspase-3, and caspase-8), fetal brains (interleukin-10, interleukin-1β, TNF-α, caspase-8, glial fibrillary acidic protein, vimentin, myelin basic protein, and receptor activator of nuclear factor kappa), and placenta tissues (interleukin-10, interleukin-1β, TNF-α, caspase-3, and caspase-8) were immunohistochemically evaluated., Results: Maternal fingolimod treatment led to attenuation of LPS-induced fetal brain, lung, and placental injury, as indicated by lower immunoexpression of inflammatory markers compared to LPS group ( p < .0001 for all comparisons)., Conclusion: The findings of the present study confirm the neuroprotective effects of antenatally administered fingolimod, which also significantly improved preterm fetal lung injury and placental inflammation in LPS-exposed preterm pregnancies by possible antiapoptotic and anti-inflammatory effects.

Cigarette smoking (CS) has some detrimental effects that occur via oxidative stress (OS). The aim of this work was to demonstrate the pathological and immunohistochemical effects of CS and the protective effects of a strong antioxidant alpha lipoic acid (ALA) on CS-induced genital system changes in a rat model. Twenty-eight female rats were randomly allocated to three groups as control, CS-exposed, and CS-exposed and ALA-treated. Reproductive tract organs were collected for biochemical and pathological examinations. In the CS group, OS markers increased in the tissues of both the ovary and fallopian tubes. Decreased follicle numbers in the ovary, marked cilial loss in the fallopian tubes, and pathologic changes in the uterus were observed in the CS group. Positive calcitonin gene-related peptide (CGRP), caspase 3α, hypoxia-inducible factor 1α (HIF-1α), tumor necrosis factor-α (TNF-α) immunoreactions were observed in uterine tissues and HIF-1α immunoreactions in tubal and uterine epithelial cells of the CS group. ALA reversed all these findings effectively. CS has negative effects on the female reproductive system via HIF-1α in tuba uterina and HIF-1α, HIF-2α, TNF-α, caspase 3, and CGRP in the uterus, and ALA could protect against the negative effects of CS on the female reproductive system.

Aim: Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury., Methods: Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry., Results: Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons)., Conclusion: Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis., (© 2017 Japan Society of Obstetrics and Gynecology.)

Prolonged use of an antineoplastic agent methotrexate (MTX), can cause numerous side effects such as nephrotoxicity. The aim of this study was to examine the effects of MTX on kidneys and demonstrate the protective effects of gallic acid (GA). Twenty-four, male, rats distributed into three groups. Each groups consisted eight rats and only saline was administered to the control group. The MTX group received a single dose (20 mg/kg) MTX intraperitoneally. The MTX + GA group received same dose MTX and 100 mg/kg GA orally during the 7 days. Renal functions, oxidative stress markers, histopathological and immunohistochemical changes were evaluated at the end of the experiment. Blood urea nitrogen, creatinine, uric acid levels and tissue oxidative stress markers, total oxidant status and oxidative stress index levels significantly increased and total antioxidant status levels significantly decreased in MTX group compared with the control group. At the histopathological examination hemorrhages, tubular cell necrosis, glomerulosclerosis, inflammatory cell infiltrations and proteinous materials in tubules were noticed in MTX group. Immunohistochemical examination revealed that increased expressions of serum amyloid A (SAA), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE-2) and C-reactive protein (CRP) in tubular epithelial cells of kidneys in this group. There were no immunoreaction with SAA and CRP, only small number of PGE-2 and TNF-α positive tubular epithelial cells were observed in MTX + GA group. In conclusion, all evidence suggested that oxidative stress caused MTX-induced nephrotoxicity and GA prevent the kidney from the nephrotoxicity due to its antioxidant and anti-inflammatory activities., (Copyright © 2017. Published by Elsevier B.V.)

The aim of this study was to investigate electromagnetic radiation (EMR) transmitted by wireless devices (2.45 GHz), which may cause physiopathological or ultrastructural changes, in the testes of rats. We addressed if the supplemental gallic acid (GA) may reduce these adverse effects. Six-week-old male Sprague Dawley rats were used in this study. Forty eight rats were equally divided into four groups, which were named: Sham, EMR only (EMR, 3 h day -1 for 30 days), EMR + GA (30 mg/kg/daily), and GA (30 mg/kg/daily) groups. Malondialdehyde (MDA) and total oxidant status (TOS) levels increased (p = 0.001 for both) in EMR only group. TOS and oxidative stress index (OSI) levels decreased in GA treated group significantly (p = 0.001 and p = 0.045, respectively). Total antioxidant status (TAS) activities decreased in EMR only group and increased in GA treatment group (p = 0.001 and p = 0.029, respectively). Testosterone and vascular endothelial growth factor (VEGF) levels decreased in EMR only group, but this was not statistically significant. Testosterone and VEGF levels increased in EMR+GA group, compared with EMR only group (p = 0.002), and also increased in GA group compared with the control and EMR only group (p = 0.044 and p = 0.032, respectively). Prostaglandin E 2 (PGE 2 ) and calcitonin gene releated peptide (CGRP) staining increased in tubules of the testes in EMR only group (p < 0.001 for both) and decreased in tubules of the testes in EMR+GA group (p < 0.001 for all parameters). In EMR only group, most of the tubules contained less spermatozoa, and the spermatozoon counts decreased in tubules of the testes. All these findings and the regenerative reaction, characterized by mitotic activity, increased in seminiferous tubules cells of the testes in EMR+GA group (p < 0.001). Long term EMR exposure resulted in testicular physiopathology via oxidative damage and inflammation. GA may have ameliorative effects on the prepubertal rat testes physiopathology. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1771-1784, 2016., (© 2015 Wiley Periodicals, Inc.)

Objectives: To evaluate the effect of learning styles and study behaviors on preclinical medical students' pharmacology exam scores in a non-Western setting., Materials and Methods: Grasha-Reichmann Student Learning Study Scale and a modified Study Behavior Inventory were used to assess learning styles and study behaviors of preclinical medical students (n = 87). Logistic regression models were used to evaluate the independent effect of gender, age, learning style, and study behavior on pharmacology success., Results: Collaborative (40%) and competitive (27%) dominant learning styles were frequent in the cohort. The most common study behavior subcategories were study reading (40%) and general study habits (38%). Adequate listening and note-taking skills were associated with pharmacology success, whereas students with adequate writing skills had lower exam scores. These effects were independent of gender., Conclusions: Preclinical medical students' study behaviors are independent predictive factors for short-term pharmacology success.

Objective: This study was designed to investigate the effects of 2450 MHz EMR on the heart and blood in rat and possible ameliorating effects of melatonin., Material and Method: Thirty-two female Wistar Albino rats were randomly grouped (by eight in each group) as follows:  Group I: cage-control group (dimethysulfoxide (DMSO), 10mg/kg/day i.p. without stress and EMR. Group II: sham-control rats stayed in restrainer without EMR and DMSO (10mg/kg/day i.p.). Group III: rats exposed to 2450 MHz EMR. Group IV: treated group rats exposed to 2450 MHz EMR+melatonin (MLT) (10mg/kg/day i.p.)., Results: In the blood tissue, there was no significant difference between the groups in respect of erythrocytes GSH, GSH-Px activity, plasma LP level and vitamin A concentration (p > 0.05). However, in the Group IV, erythrocytes' LP levels (p < 0.05) were observed to be significantly decreased while plasma vitamin C, and vitamin E concentrations (p < 0.05) were found to be increased when compared to Group III. In the heart tissues, MDA and NO levels significantly increased in group III compared with groups I and II (p < 0.05). Contrary to these oxidant levels, CAT and SOD enzyme activities decreased significantly in group III compared with groups I and II (p 0.05). Besides, MLT treatment lowered the MDA and NO levels compared with group III., Discussion: In conclusion, these results demonstrated that contrary to its effect on the heart, the wireless (2450 MHz) devices cause slight oxidative-antioxidative changes in the blood of rats, and a moderate melatonin supplementation may play an important role in the antioxidant system (plasma vitamin C and vitamin E). However, further investigations are required to clarify the mechanism of action of the applied 2450 MHz EMR exposure (Tab. 3, Fig. 1, Ref. 49).