Beta-glucan attenuates cerebral ischemia/reperfusion-induced neuronal injury in a C57BL/J6 mouse model

Beta-glucans (βg), that have many useful effects on human health, are natural polysaccharides. Our aim in this study was to determine useful effect of βg against oxidative and neuronal damage caused by global cerebral ischemia/reperfusion (IR) in stroke imitated mice via surgical operation. A total of 40 mice divided into four equal groups randomly. The group 1 (sham operated) was kept as control. Bilateral carotid arteries of subjects in group 2 (I/R) and group 4 (I/ R + βg) were clipped for 15 min, and the mice in group 4 (I/R + βg) were treated with βg (50 mg/kg/day), while the mice in group 2 (I/R) were treated with only vehicle for 10 days. The mice of group 3 (βg) were treated with βg for 10 days without carotid occlusion. Global cerebral I/R significantly increased oxidative stress and decreased members of antioxidant defense system. In addition, I/R caused histopathological damage in the brain tissue. However, βg treatment ameliorated both oxidative and histopathological effects of I/R. Our present study showed that βg treatment significantly ameliorated oxidative and histological damage in the brain tissue caused by cerebral I/R. Therefore, βg treatment can be used as supportive care for ischemic stroke patients

THE PROTECTIVE EFFECTS OF TETRANDRINE AGAINST TO HISTOLOGICAL, SPERMATOLOGICAL AND OXIDATIVE DAMAGE INDUCED BY AROCLOR 1254 ON THE MALE RATS REPRODUCTIVE SYSTEM

Objectives: Aroclor (AR) 1254; has many adverse effects on male reproduction such as carcinogenic, teratogenic, immune and endocrine disruption problems. Tetrandrine (TET), a bisbenzillisoquinoline alkaloid isolated from the root of Stephania tetrandra S. Moore, has protective effects such as immunomodulatory, anti-cancer, and anti-inflammatory. The objective of this study was to investigate the possible curative effects of TET therapy against testicular damage (histological, spermatological and oxidative damage) induced by AR1254. Materials and Methods: Twenty-eight male rats were randomly divided into four equal-sized groups: a control group; (1 ml of corn oil by gastric oral gavage), AR1254 group; (2 mg/kg) AR1254 administered intraperitoneally), TET group; (TET by gastric oral gavage 30 mg/kg) and AR 1254 + TET group;(Aroclor 1254 and TET administered together at the same doses as the previous groups. Results: The AR1254 treatment caused morphological and spermatological damage on testis tissue; oedema vacuolization and congestion, in interstitial area, reduction in spermatogenic cells, arrested spermatocytes at different stages of spermatogenesis, shedding of spermatogenic serial cells into tubular lumens, a decline in epididymal sperm concentrations, sperm motility and a rise in abnormal sperm ratios. The AR1254 administration induced an increase in the oxidative parameters and a decrease in enzymatic and nonenzymatic antioxidant levels. The TET treatment significantly ameliorated histological, oxidative, and sperm damage caused by AR1254. Conclusion: This study demonstrated the protective effects of TET against AR1254-induced male rat reproductive damage

Drug-Drug Interaction of Aldehyde Oxidase Inhibitor and Xanthine Oxidase Inhibitor with Favipiravir

Aim: Favipiravir is an effective antiviral used in the treatment of COVID-19. It is metabolized by aldehyde oxidase (AO) and xanthine oxidase (XO). This study investigated drug-drug interactions between favipiravir with both AO substrate and XO enzyme inhibitor, allopurinol, and an XO inhibitor, verapamil. Material and Methods: 25 Sprague-Dawley female rats, 250-300 g, were divided into five equal groups. Blood samples were taken from the jugular vein at the end of 0, 15, 30, and 45 minutes, and at the end of the 1st, 2nd, 4th, 6th, and 8th hours after the drugs were administered. The drug-blood concentration was determined in the HPLC-UV device using plasma. The ELISA method measured AO and XO enzyme activities in rat liver tissue. Results: Allopurinol prolonged the time taken for favipiravir to reach Cmax (Tmax), decreased maximum serum concentration (Cmax), elimination half-life (T1/2), area under the curve (AUC), and mean residence time (MRT). Allopurinol significantly reduced clearance per unit time (Cl/f) when co-administered with favipiravir. Verapamil accelerated the elimination of favipiravir, significantly reducing T1/2, MRT, and AUC. On the other hand, Favipiravir decreased the absorption of verapamil and slowed its elimination. Cmax, AUC, and Cl values of verapamil decreased. In addition, T1/2, MRT, and volume of distribution (Vd) increased. Conclusion: In conclusion, the concomitant use of favipiravir with other drugs that affect AO and/or XO enzyme activities may cause changes in the pharmacokinetic profiles of drugs and the levels of enzymes that metabolize drugs

EGFR blocker lapatinib inhibits the synthesis of matrix metalloproteinases from synovial fibroblasts

Background/aim: Epidermal growth factor receptor (EGFR) family members and their associated ligands may be related to bone and joint destruction in rheumatoid arthritis. Matrix metalloproteinases are responsible for joint and bone tissue degradation. This study is intended to investigate the effect of epidermal growth factor receptor inhibition by lapatinib on the synthesis of matrix metalloproteinases in in vitro. Materials and methods: Synovial fibroblast cell culture was obtained from a patient with rheumatoid arthritis who underwent knee arthroplasty. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were added to the cell culture to stimulate synovial fibroblast cells and create an inflammatory character. Understimulated and nonstimulated conditions, lapatinib was applied to the culture in four different concentrations of 25, 50, 100, and 200 µmol. Then, matrix metalloproteinase-1,-3, and,-13 levels were assessed. Results: When stimulated with IL-1β and TNF-α, the synthesis of matrix metalloproteinases from synovial fibroblast was increased significantly. When lapatinib is added to the stimulated synovial fibroblasts, matrix metalloproteinases synthesis is significantly suppressed. Conclusion: Inhibition of the EGFR pathway with lapatinib suppresses matrix metalloproteinases synthesis. Our results suggest EGFR pathway inhibition may be a promising option to prevent joint destruction in the treatment of rheumatoid arthritis

Taurine prevents against 2,3,7,8 - tetrachlorodibenzo-p-dioxin-induced oxidative stress in the liver and kidney of rats

Objective: The aim of the study was to investigate the preventive effects of taurine against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced organ damage in rats. The environmental toxin TCDD has a high toxicity in animal and human tissues. Taurine is an amino acid found in many organs, with multiple physiological roles including the protection of cells with its antioxidant and anti-inflammatory properties. In this context, our aim in this study was to investigate the potential preventive effect of taurine on oxidative stress and organ damage caused by TCDD in rat liver and kidney tissues. To evaluate these possible effects, we measured the levels of thiobarbituric acid reactive substances (TBARS), and glutathione (GSH), as well as the activity of superoxide dismutase © 2023 University of Ankara. All rights reserved.The authors are grateful to Yasemin ŞAHİN for contributions in biochemical calculations

Protective role of diospyros lotus l. in cisplatin-induced cardiotoxicity: Cardiac damage and oxidative stress in rats

Objectives: Cisplatin is a powerful chemotherapeutic drug that is used to treatment a wide variety of cancers. Despite clinical data demonstrating the cardiotoxic effect of cisplatin, few studies have been carried to improve the cardiotoxicity of cisplatin. In cisplatin-induced toxicity, oxidative stress plays a critical role. This study determined the effect of Diospyros lotus L. fruit (DL), a powerful antioxidant plant, on heart damage caused by cisplatin through histological examination and oxidative stress parameters. Materials and Methods: Twenty eight male rats were randomly divided into four groups. An isotonic solution was given to the control group. A single dose of 7 mg/kg cisplatin was administered intraperitoneally to the cisplatin group. 1.000 mg/kg DL was given by gavage for 10 days to the DL group. Cisplatin and DL were administered together in the same doses to the treatment group. Thiobarbituric acid reactive substances (TBARS) levels, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and total glutathione (GSH) level were measured in the heart tissue of the experimental rats. Histological examination was also performed to determine any damage to the hearts of the experimental rats. Results: While TBARS levels in the cisplatin group increased significantly, SOD, CAT, GPx activities, and total GSH level decreased significantly. TBARS levels decreased significantly and SOD, CAT, GPx activities and GSH levels increased with DL treatment. According to the histological examination, histopathological differences were observed in the cisplatin group. Histopathological findings were either absent or decreased in the DL-treated group. Conclusion: Results of the study showed that DL therapy reduced oxidative stress and histological changes caused by cisplatin. DL could be a potential candidate for reducing cardiac damage caused by cisplatin

18β-glycyrrhetinic acid attenuates global cerebral ischemia/reperfusion-induced cardiac damage in C57BL/J6 mice

Abstract The aim of the present study is to investigate the cardioprotective effects of 18β-glycyrrhetinic acid (18β -GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 18β-GA, and (4) 18β -GA+I/R. Ischemia was not applied to the sham and 18β-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 18β-GA group, the mice were given 18β-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 18β-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 18β-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 18β-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 18β-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment

The inhibition of src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits mapk and stats pathways

Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings. Materials and methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP –1, –3, and –13 levels in FLSs culture were determined by ELISA. Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP –1, –3, and –13 expressions from FLSs induced by IL-1β and TNF-α were increased, while dasatinib suppressed their productions from FLSs. Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA

Nerolidol attenuates dehydroepiandrosterone-induced polycystic ovary syndrome in rats by reGülating oxidative stress and decreasing apoptosis

Aims: Although nerolidol (NRL) is a naturally occurring sesquiterpene alcohol with many pharmacological ac-tivities, its role in dehydroepiandrosterone DHEA-induced polycystic ovary syndrome PCOS is unknown. This study aims to explore the potential beneficial effects and underlying molecular mechanisms of nerolidol treat-ment on polycystic ovary syndrome.Main methods: Pre-pubertal female Sprague-Dawley rats were randomly assigned into four groups (n = 8/group); group I: control; group II: PCOS; group III: P + NRL; group IV: NRL. Biochemical parameters related to oxidative stress, inflammation, apoptosis, and hormones were estimated in the blood and ovarian tissues. Histopatho-logical, ultrastructural, and immunohistochemical analyses were performed. Bax, P53, Cas-3, and Bcl-2 gene expression levels were detected with RT-PCR. The membrane array analysis detected chemokine, cytokine, and growth factor protein profiles.Key findings: In light of the available data, it can deduce that nerolidol has a significant ameliorating effect on lipid peroxidation, oxidative stress, inflammation, histopathological damage, and apoptosis accompanying PCOS in female rats.Significance: PCOS is not only a reproductive pathology but also a systemic condition and its etiopathogenesis is still not fully understood. Sİnce changes in PCOS have important long-term effects on health, this study evaluated the efficacy of nerolidol, a phytotherapeutic for the control of biochemical, apoptotic, histopathological, and metabolic changes.Inonu University Department of Scientific Research Projects [TCD-2020-2090]This study was supported by the Inonu University Department of Scientific Research Projects (Project number: TCD-2020-2090, Turkiye)

Investigation of the Protective Effect of Nerolidol on Dehydroepiandrosterone-induced Polycystic Ovary Syndrome in Female Rats

[No Abstract Available]Inonu University Scientific Research Projects Coordination Unit [TCD-2020/2090]This study was supported by Inonu University Scientific Research Projects Coordination Unit (Project Number: TCD-2020/2090)