Hepatoprotective actions of melatonin by mainly modulating oxidative status and apoptosis rate in lipopolysaccharide-induced liver damage

Aim: One of the serious complications of sepsis is liver damage and liver failure. This study aimed to evaluate the protective and therapeutic potential of melatonin in rats with lipopolysaccharide-induced sepsis. Main methods: Female Spraque–Dawley rats received single a dose of 7.5 mg/kg lipopolysaccharide in saline to create a 24-h sepsis model. One of the other groups received melatonin at a dose of 10 mg/kg/day beginning 1 week before sepsis induction to the end of the experiment. The melatonin group received the same doses of melatonin for the same duration but not lipopolysaccharide. The vehicle group received the same doses of saline, the vehicle of melatonin, for the same duration. Twenty-four hours after the last injection, the rats were decapitated. By appropriate histochemical, immunohistochemical, biochemical, and molecular techniques, anti-necrotic, anti-apoptotic, anti-necroptotic, anti-inflammatory, and antioxidant effects of melatonin were assessed. Key findings: Lipopolysaccharide has disrupted liver functions by inducing oxidative stress, inflammation, necrotic, apoptotic, and necroptotic cell death, thus disrupting liver functions. Melatonin was found to be beneficial in terms of inhibiting the intrinsic pathway of apoptosis and tissue oxidant levels, stimulating tissue antioxidant enzyme levels, and restoring hepatocyte functions. Significance: Melatonin, at those doses and duration, was found to be hepatoprotective by mainly modulating oxidative status and apoptosis rate, however, failed to significantly reduce histopathological damage. We suggest that longer-term melatonin administration may produce anti-inflammatory and anti-necrotic effects as well. © 2023 Informa UK Limited, trading as Taylor & Francis Group

Performance of neutrophil to lymphocyte ratio for the prediction of long-term morbidity and mortality in coronary slow flow phenomenon patients presented with non-ST segment elevation acute coronary syndrome

Introduction: In this study, we aimed to determine if neutrophil to lymphocyte ratio could predict long term morbidity and mortality in patients who hospitalized for non-ST segment elevation acute coronary syndrome (NSTE-ACS) and had coronary slow flow on coronary angiography. Methods: In this observational study, 111 patients who presented with NSTE-ACS and diagnosed with coronary slow flow phenomenon on angiographic examination were included. Neutrophil to lymphocyte ratio (NLR) calculated as the ratio of the number of neutrophils to the number of lymphocytes. Patients classified into three groups according to NLR values. The term coronary slow flow phenomenon was depicted by calculating Thrombolysis in Myocardial Infarction frame count.Patients were followed up and the occurrence of recurrent angina, recurrent myocardial infarction, and long-term mortality was determined using medical records, phone calls, or face-to-face interviews. P values <0.05 considered to indicate statistical significance. Results: Recurrent angina and myocardial infarction occurred more frequently in the highest NLR tertile compared with middle and lowest NLR tertiles. High NLR group (NLR≥ 3.88 n=38) was significantly associated with younger age and smoking status. WBC, troponin I and CRP levels increased as the NLR tertile increased. Recurrent myocardial infarction and angina showed strong relationship with increasing NLR values. In multivariate regression analyses smoking and high NLR levels were independent predictors of recurrent myocardial infarction (HR:4.64 95%CI 0.95-22.52 P=0.04, HR: 1.48 95%CI 1.16-1.90 P<0.01 respectively) in the long term follow up. Conclusion: Our study demonstrated that high NLR values can be a valuable prognostic tool in the long term follow up of patients who presented with NSTE-ACS and diagnosed with slow flow phenomenon on coronary angiography

Thymoquinone ameliorates delayed cerebral injury and cerebral vasospasm secondary to experimental subarachnoid haemorrhage

Aim of the study. Among subarachnoid haemorrhage (SAH) patients, delayed cerebral injury (DCI) and infarction are the most important causes of death and major disability. Cerebral vasospasm (cVS) and DCI remain the major cause of death and disability. Thymoquinone (TQ) is the substance most responsible for the biological activity of nigella sativa (NS) and is useful in the treatment of ischaemic and neurodegenerative diseases, oxidative stress, inflammatory events, cardiovascular and neurological diseases. We conducted an experimental study aimed to investigate the preventive and corrective effects of TQ.Materials and methods. 24 Sprague-Dawley rats were randomly divided into three groups. The first was the control group which was a sham surgery group. The second group was the SAH group where the double haemorrage SAH protocol was used to induce vasospasm. The third group was the SAH+TQ group, where cVS was induced by the SAH protocol and the animals received oral 2 cc thymoquinone solution for seven days at a dose of 10 mg/kg, after the induction of SAH. The rats were euthanised seven days after the first procedure. The degree of cerebral vasospasm was evaluated by measuring the basilar artery luminal area and arterial wall thickness. Apoptosis was measured by the western blot method at brainstem neural tissue. Oxidative stress was measured by the Erel Method. Endothelin-1 was measured with ELISA analysis at blood. Statistical analysis was performed.Results. Endothelin-1 values were found to be statistically significantly lower in the control and SAH+TQ groups compared to the SAH group (P < 0.001). Mean lumen area values were significantly higher in the control and SAH+TQ groups than in the SAH group (P < 0.001). In the control and SAH+TQ groups, wall thickness values decreased significantly compared to the SAH group (P < 0.001). OSI values were significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001). Apoptosis was significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001).Conclusion. Our results show that post-SAH TQ inhibits/improves DCI and cVS with positive effects on oxidative stress, apoptosis, ET-1, lumen area, and vessel wall thickness, probably due to its anti-ischaemic, antispasmodic, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective effects

Effects of a thermosensitive in situ gel containing mometasone furoate on a rat allergic rhinitis model

WOS: 000432900700002PubMed ID: 29644886Background: Mometasone furoate, one of the second generation intranasal corticosteroids, is currently used in suspension form due to its poor solubility. However, this is not favorable for nasal application because of the rapid elimination of the instilled drug from the nasal cavity by mucociliary clearance and delayed onset of action due to the slow dissolution of drug in suspension. Objective: The aim of this study was to determine the antiallergic effects of mucoadhesive thermosensitive in situ gel containing mometasone furoate that we developed previously to prolong the contact between the drug and nasal mucosa and to prevent drainage of the formulation in an ovalbumin-induced rat model of allergic rhinitis. Methods: An experimental allergic rhinitis model was developed in female Wistar albino rats by intraperitoneal injection of ovalbumin every 2 days for 14 days followed by its repeated intranasal instillation for 7 consecutive days. Intranasal instillation of ovalbumin was continued every other day for 14 days. Mometasone furoate in situ gel (5 mu g/10 mu l), mometasone furoate suspension (5 mu g/10 mu l), and physiological saline (10 ml) were administered into the bilateral nasal cavities from day 22 to day 35. Antiallergic effects were evaluated through histopathological evaluation, analysis of ovalbumin-specific serum immunoglobulin E, and a symptom score. Results: Mometasone furoate in situ gel significantly decreased the nasal symptoms and ovalbumin-specific serum immunoglobulin E level as compared with mometasone furoate suspension and physiological saline. Additionally, inflammatory histological symptoms such as mucosal edema, vascular dilatation, eosinophil infiltration, and loss of cilia within the nasal mucosa of allergic rhinitis model rats were remarkably improved with the treatment of mometasone furoate in situ gel. Conclusion: These results suggest that mometasone furoate in situ gel has a better therapeutic potential for the treatment of allergic rhinitis compared to mometasone furoate suspension.Scientific Research Project Coordination Unit of Istanbul University [41584]; TUBITAK (The Scientific & Technological Research Council of Turkey) [114S820, 1002]The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Scientific Research Project Coordination Unit of Istanbul University (Project Number: 41584) and Rapid Support Program (1002) of TUBITAK (The Scientific & Technological Research Council of Turkey (Project Number: 114S820)

Clemizole hydrochloride, a potent TRPC5 calcium channel inhibitor, prevents cisplatin-induced nephrotoxicity in Spraque-Dawley rats.

Cis-diamminedichloroplatinum (II) (cisplatin, Cis) is widely employed to treat several types of cancer. It has many important toxic side effects; one of the most important of which is nephrotoxicity. Clemizole hydrochloride (Clem) as the most potent inhibitor of TRPC5 channels was tested in an animal model of Cis-induced nephrotoxicity. Rats were divided into the following groups: control; Cis (8 mg/kg); Cis + 1 mg/kg Clem; Cis + 5 mg/kg Clem; Cis + 10 mg/kg Clem. Kidney injury was detected by histopathological and biochemical analysis. Urine urea nitrogen (UUN), creatinine, urine neutrophil gelatinase-associated lipocalin (NGAL), serum catalase (CAT), and malondialdehyde (MDA) levels were determined by enzyme-linked immunosorbent assay. Total antioxidant status (TAS) and total oxidant status (TOS) were studied using a colorimetric assay. Nephrin, synaptopodin, and Rac family small GTPase 1 (RAC1) expressions were detected by Western blot analysis. Cis was found to induce histopathological alterations, including tubular degeneration, congestion, hemorrhage, hyaline casts, glomerular collapse, and apoptotic cell death. Clem at a dose of 1 and 5 mg/kg attenuated histopathological alterations. UUN, creatinine, and NGAL levels increased in the Cis-administered group, while all doses of Clem decreased in those. CAT and TAS levels decreased, while TOS and oxidative stress index levels increased in the Cis-treated group. A dose of 1 and 5 mg Clem showed antioxidant effects against oxidative stress. Cis induced lipid peroxidation by increasing MDA levels. All doses of Clem reduced MDA levels. Nephrin and synaptopodin expressions were decreased by Cis, and all doses of Clem increased that. All doses of Clem successfully depressed RAC1 expression. Clem showed a highly ameliorating effect on toxicity caused by Cis by blocking TRPC5 calcium channels.</p

Chemical Composition, Antimicrobial and Antioxidant Activities of Hyssop (Hyssopus officinalis L.) Essential Oil

The essential oil of hyssop is widely used in food, pharmaceutical and cosmetic industries throughout the world. Therefore, it is very important to know the chemical characteristics of the oil for economic use and enhanced performance of the end products. This study was carried out to determine antimicrobial and antioxidant activities of the essential oil of Hyssopus officinalis (L.) (Lamiaceae) collected from wild in the Southeast Anatolian, Turkey. Chemical compositions of hydrodistilled essential oils obtained from hyssop leaves were analyzed by gas chromatography-mass spectrometry (GC-MS). For antimicrobial activity, disc diffusion tests were carried out on Escherichia coli line ATCC25922, Pseudomonas aeroginosa line ATCC27853, Staphylococcus aureus line 25923, Staphylococcus pyogenes line ATCC19615 and Candida albicans line ATCC10231, and the antioxidant activity was determined by using the diphenylpicrylhydrazyl (DPPH) radical-scavenging method. It was determined that hyssop essential oil contained isopinocamphone (57.27%), (-)-?-pinene (7.23%), (-)-terpinen-4-ol (7.13%), pinocarvone (6.49%), carvacrol (3.02%), p-cymene (2.81%) and myrtenal (2.32%) as major components. As shown by treatments with 5 and 10 ?l of oil; which exhibited strong antimicrobial activity against S. pyogenes, S. aureus, C. albicans and E. coli, but not against P. aeruginosa. The antioxidant activity of H. officinalis essential oil was lower compared to butylated hydroxytoluene (BHT) and ascorbic acid. These results demonstrated that hyssop essential oil has relatively low antioxidant activity and good antimicrobial activity against some test organisms

Therapeutic effects of metformin for noise induced hearing loss

Objective: This study aimed to investigate the healing effect of metformin on noise induced hearing loss (NIHL) by measuring audiological, biochemical and histological parameters.Materials and methods: 32 rats were divided into four groups (Group 1: Noise, Group 2: Noise + Metformin, Grup 3: Metformin, Grup 4: Control). Broadband noise was applied to Group 1 and Group 2 after basal measurements. Measuring audiological (distortion product otoacoustic emission (DPOAE) and Auditory Brainstem Response (ABR)), biochemical (total antioxidant status (TAS), total oxidant status (TOS), oxidative status index (OSI), DNA damage, IL-1 beta, IL-6, TNF alfa, HSF-1 and COX-2) and histological parameters.Results: Group 2 had significant decreases in ABR thresholds on day 7 and day 14 compared to day 1. DPOAE values of Group 2 on the 7th and 14th days were significantly higher than the post-noise levels. DNA damage, TOS and OSI values of Group 1 were significantly higher than the other groups. The Cox-2 value of Group 1 was higher than all other groups. The HSF-1 value of Group 2 was significantly higher than that of Group 1. In terms of IL-1 Beta, IL-6 and TNF-alpha values, there was no significant difference between groups 2, 3 and 4 and these values were significantly lower than group 1. In histopathological results of our study, no significant difference was found between the groups being exposed to noise and the control group.Conclusion: This study showed that early period of Metformin treatment has therapeutic effect on NIHL