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1.
J Biochem Mol Toxicol ; 38(1): e23582, 2024 Jan.
Article En | MEDLINE | ID: mdl-37975510

Although diclofenac (DCF) is a nonsteroidal anti-inflammatory drug that is considered safe, its chronic use and overdose may show some toxic effects. The protective effect of tyrosol (Tyr) pretreatment against DCF-induced renal damage was investigated in this study. The 32 rats used in the study were randomly divided into four groups of eight rats each. According to the data obtained, it was determined that creatinine, urea, and blood urea nitrogen (BUN) levels increased in serum samples of the DCF group. Besides, the levels of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity decreased and the malondialdehyde (MDA) level increased in the kidney tissue. However, no change was observed in catalase (CAT) activity. Cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (Tnf-α) levels increased and nuclear factor erythroid 2-related factor 2 (Nrf-2) levels decreased. No change was detected in the level of interleukin 1 beta (IL-1ß). When the DCF+Tyr group and the DCF group were compared, it was assessed that Tyr had a curative effect on all biochemical parameters. Also, kidney damages, such as degeneration and necrosis of tubular epithelium and congestion of veins, were obviated by treatment with tyrosol in histopathological examinations. It was determined that Tyr pretreatment provided a protective effect against nephrotoxicity induced by DCF with its anti-inflammatory and antioxidant properties.


Diclofenac , Phenylethyl Alcohol/analogs & derivatives , Renal Insufficiency , Rats , Animals , Diclofenac/toxicity , Oxidative Stress , Kidney , Antioxidants/pharmacology , Antioxidants/metabolism , Glutathione/metabolism , Anti-Inflammatory Agents/pharmacology
2.
J Biochem Mol Toxicol ; 38(1): e23528, 2024 Jan.
Article En | MEDLINE | ID: mdl-37661762

AIMS: Ovarian ischemia-reperfusion (I/R) injury is a phenomenon that necessitates urgent intervention, which occurs as a result of ovarian torsion, and it is frequently seen in young women. A large amount of free radical and oxidative damage as a result of I/R plays a role in the cause of the incident. Antioxidant agents are thought to be beneficial in preventing this damage, and the potential protective effects of esculetin, which had not been tested previously, were investigated in this study. STUDY DESIGN: The rats in the study were divided into five groups at random: control, sham, esculetin, I/R, and treatment. Oxidative stress parameters, proinflammatory cytokines, nuclear factor erythroid 2-related factor 2 (Nrf-2)/nuclear factor-kß (NF-κß) pathway, and histopathological analyses were evaluated at the end of the study. KEY FINDINGS: After I/R, malondialdehyde levels, proinflammatory cytokines, tumor necrosis factor-α and interleukin-1ß levels and NF-κß expressions were increased, Nrf-2 expression and glutathione level decreased and the histopathologic picture deteriorated. However, as a result of the esculetin treatment, ameliorative effects in the aforementioned parameters were determined, and it was ensured that they returned to normal levels. CONCLUSION: According to these findings, esculetin has protective effects on I/R damage by lowering lipid peroxidation and having antioxidant and anti-inflammatory properties. SIGNIFICANCE: Our results proved the protective effect of esculetin against ovarian IR injury in rats and this may be attributed to Nrf-2/NF-κß axis which showed antioxidant and anti-inflammatory effects. Therefore, esculetin can be used in the future for preventive effects to ovarian IR injury.


Ovarian Diseases , Reperfusion Injury , Umbelliferones , Humans , Rats , Female , Animals , Antioxidants/metabolism , Rats, Wistar , Reperfusion Injury/drug therapy , Reperfusion Injury/prevention & control , Reperfusion Injury/metabolism , Oxidative Stress , Anti-Inflammatory Agents/pharmacology , Tumor Necrosis Factor-alpha/metabolism
3.
Biotech Histochem ; 98(4): 255-266, 2023 May.
Article En | MEDLINE | ID: mdl-37165766

Increased pro-inflammatory cytokines and oxidative stress contribute to the pathophysiology of ulcerative colitis (UC). Inula viscosa is a plant with antioxidant and anti-inflammatory properties. We investigated the effect of an ethanolic extract of I. viscosa on an experimental UC model created using acetic acid. Rats were divided into four groups of eight: group 1, control; group 2, 3% acetic acid group; group 3, 100 mg/kg sulfasalazine + 3% acetic acid group; group 4, 400 mg/kg I. viscosa + 3% acetic acid. I. viscosa and sulfasalazine were administered by oral gavage and 3% acetic acid was administered per rectum. We found that I. viscosa treatment decreased colon malondialdehyde, tumor necrosis factor-α, interleukin-1 beta and nuclear factor kappa B levels; it increased reduced glutathione, nuclear factor erythroid 2-related factor 2, heme oxygenase-1 and kelch-like ECH-associated protein 1 levels and glutathione peroxidase enzyme activity. Group 1 colon exhibited normal histological structure. Slight inflammatory cell infiltration and edema and insignificant slight erosion in crypts were detected in colon tissues of group 4. We found that I. viscosa reduced oxidative stress and inflammation, which was protective against UC by inducing the Nrf-2/Keap-1/HO-1 pathway in the colon.


Colitis, Ulcerative , Inula , Rats , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Sulfasalazine/pharmacology , Inula/metabolism , Acetic Acid , Antioxidants/pharmacology , Antioxidants/metabolism
4.
Biotech Histochem ; 98(1): 69-76, 2023 Jan.
Article En | MEDLINE | ID: mdl-36444536

We induced experimental nephrolithiasis in female rats using ethylene glycol (EG) and ammonium chloride (AC). We investigated the effects of carvacrol, an essential oil with antioxidant and anti-inflammatory properties, on nephrolithiasis using histopathology, immunohistochemistry and biochemistry. We used 40 female rats divided into four equal groups: control group, administered olive oil; carvacrol group, administered carvacrol in olive oil; nephrolithiasis group, administered EG and AC to induce experimental nephrolithiasis; treatment group with induced nephrolithiasis and administered carvacrol in olive oil. We observed no significant difference in crystal accumulation in the treatment group compared to the nephrolithiasis group. We found a significant reduction in hydropic degeneration of tubules and degree of inflammatory cell infiltration of intertubule areas. We also found a significant reduction in immunohistochemical staining of macrophage- and monocyte-specific antigens. Carvacrol treatment reversed the induced nephrolithiasis, increased malondialdehyde and urea, and decreased levels of glutathione peroxidase and catalase. Although carvacrol did not decrease crystal accumulation, it reduced pathological and biochemical damage, and improved kidney function by lowering the serum urea level.


Nephrolithiasis , Female , Rats , Animals , Olive Oil/pharmacology , Rats, Wistar , Nephrolithiasis/chemically induced , Nephrolithiasis/drug therapy , Nephrolithiasis/pathology , Antioxidants/pharmacology , Antioxidants/metabolism , Ethylene Glycol/adverse effects , Urea/adverse effects , Oxidative Stress , Thymol
5.
J Biochem Mol Toxicol ; 36(9): e23140, 2022 Sep.
Article En | MEDLINE | ID: mdl-35674002

Rheumatoid arthritis (RA) is a systemic chronic disease characterized by inflammation and synovitis. More effective treatment methods with less side effects need to be developed. In this context, current study investigated the therapeutic effects of safranal in a model of complete Freund's adjuvant (CFA)-induced RA. The control group was given 1 ml of saline orally starting from the 8th day, and 0.2 ml of CFA was given to the RA, RA + Safranal and RA + Methotrexate (MTX) groups on the 0th day of the experiment. Starting from the 8th day of the experiment, 1 ml of saline was given to the RA group, safranal was given at 200 mg/kg of body weight to the RA + MTX group, and 3 mg/kg of MTX to the RA + MTX group twice a week. The results showed that weight gain decreased in the RA group compared to the control group while arthritis index score, thymus index, and planter temperature were found to be increased. Additionally, a deterioration in blood parameters, an increase in alanine aminotransferase, aspartate aminotransferase, urea, creatinine, C-reactive protein, and malondialdehyde levels, and a decrease in reduced glutathione levels and glutathione peroxidase and catalase (CAT) activities were seen while tumor necrosis factor-α, interleukin-6 (IL-6), cyclooxygenase-2, nuclear factor kappa B levels were found to be increased. However, the safranal had a regulatory effect on all the values, except IL-6 and CAT, and blood parameters. Moreover, histopathological examination revealed that safranal reduced inflammatory cell infiltration and edema.


Arthritis, Experimental , Arthritis, Rheumatoid , Alanine , Animals , Antioxidants/therapeutic use , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/metabolism , Aspartate Aminotransferases , C-Reactive Protein , Catalase/metabolism , Creatinine , Cyclohexenes , Cyclooxygenase 2 , Freund's Adjuvant , Glutathione/metabolism , Glutathione Peroxidase , Interleukin-6/metabolism , Malondialdehyde , Methotrexate/pharmacology , NF-kappa B/metabolism , Rats , Terpenes , Tumor Necrosis Factor-alpha/metabolism , Urea
6.
J Food Biochem ; 46(8): e14161, 2022 08.
Article En | MEDLINE | ID: mdl-35347733

The protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-α and NF-κB levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. PRACTICAL APPLICATIONS: Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.


Reperfusion Injury , Smilax , Spermatic Cord Torsion , Animals , Anthocyanins/metabolism , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Antioxidants/metabolism , Chromatography, Liquid , Humans , Male , Plant Extracts/metabolism , Plant Extracts/pharmacology , Rats , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & control , Seeds/metabolism , Spermatic Cord Torsion/drug therapy , Spermatic Cord Torsion/metabolism , Spermatic Cord Torsion/pathology , Tandem Mass Spectrometry , Testis
7.
Drug Chem Toxicol ; 45(3): 1054-1065, 2022 May.
Article En | MEDLINE | ID: mdl-32781857

The clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.


Methotrexate , Oxidative Stress , Animals , Antioxidants/metabolism , Apoptosis , Caspase 3/metabolism , Guaiacol/analogs & derivatives , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/prevention & control , Kidney , Liver , Methotrexate/toxicity , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats
8.
J Food Biochem ; 45(11): e13965, 2021 11.
Article En | MEDLINE | ID: mdl-34636053

Liver fibrosis, which still does not have a standard treatment due to its complex pathogenesis, is an important cause of mortality and morbidity. In this study, it was aimed to examine the possible protective and antifibrotic effects of tyrosol on the liver through histopathologic, immunohistochemical, biochemical, and molecular methods in rats with chronic liver damage induced by thioacetamide (TAA). The study was carried out in four groups with eight rats in each group. Created groups are, respectively, control, TAA, tyrosol and TAA +tyrosol. Chronic liver damage was induced in the TAA and TAA +tyrosol groups by the addition of TAA (200 mg/L) to drinking water. Tyrosol (20 mg/kg/b.w./daily) was administered by oral gavage to tyrosol and TAA +tyrosol groups for 10 weeks. The results of this study demonstrate that the consumption of tyrosol alleviated the histopathologic changes such as inflammation, degeneration, and especially fibrosis induced by TAA in the liver. In addition, administration of tyrosol significantly attenuated alpha-smooth muscle actin (α-SMA) expression and apoptosis expression. Biochemically, it was determined that tyrosol increased glutathione (GSH) level, glutathione peroxidase (GSH.Px), and catalase (CAT) activities and showed antioxidant efficacy by reducing malondialdehyde (MDA) level. Moreover, it reduced inflammation and fibrosis by decreasing gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-ß1). Western blot analysis also revealed similar results in TGF-ß1 expression. As a result, tyrosol suppressed fibrogenesis thanks to its antioxidant, anti-inflammatory, and anti-apoptotic effects and showed an antifibrotic effect in the liver. PRACTICAL APPLICATIONS: It is stated that tyrosol, a natural phenolic antioxidant found in olive oil, has neuroprotective, cardioprotective, anti-inflammatory, and anticancer properties. In this study, tyrosol suppressed fibrogenesis thanks to its antioxidant, anti-inflammatory, and anti-apoptotic effects and showed an antifibrotic effect in the liver. Olive oil has an important place in the Mediterranean diet, which reduces the incidence of chronic diseases. It is thought that the anti-fibrotic effect of tyrosol plays a role in this feature. As a result, it is thought that tyrosol can be used to prevent or slow down chronic liver diseases.


Oxidative Stress , Thioacetamide , Animals , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/prevention & control , Phenylethyl Alcohol/analogs & derivatives , Rats , Thioacetamide/toxicity
10.
Inflammation ; 44(6): 2246-2259, 2021 Dec.
Article En | MEDLINE | ID: mdl-34515957

Acute lung injury (ALI) is one of the most common causes of death in diseases with septic shock. Oleuropein, one of the important components of olive leaf, has antioxidant and anti-inflammatory effects. The objective of this study was to investigate the effects of oleuropein on lipopolysaccharide (LPS)-induced ALI in rats. Oleuropein was administered to rats at a dose of 200 mg/kg for 20 days and LPS was given through intratracheal administration to induce ALI. The study was terminated after 12 h. The results showed that in the group treated with oleuropein, inflammatory cytokines and oxidative stress decreased in serum, bronchoalveolar lavage fluid (BALF), and lung tissue, and there were significant improvements in the picture of acute interstitial pneumonia (AIP) caused by LPS in histopathological examination. Based on the findings of the present study, oleuropein showed protective effects against LPS-induced ALI.


Acute Lung Injury/prevention & control , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Iridoid Glucosides/pharmacology , Lung/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Animals , Cytokines/metabolism , Disease Models, Animal , Inflammation Mediators/metabolism , Lipopolysaccharides , Lung/metabolism , Lung/pathology , Male , Neutrophil Infiltration/drug effects , Oxidative Stress/drug effects , Rats, Wistar
11.
Naunyn Schmiedebergs Arch Pharmacol ; 394(10): 2061-2075, 2021 10.
Article En | MEDLINE | ID: mdl-34287677

Asthma is an inflammatory disease that affects many people around the world, especially persons at paediatric age group. The effectiveness of tyrosol, a natural phenolic compound, was examined in the asthma model induced by ovalbumin (OVA). For this purpose, four groups, each consisting of eight rats, were arranged. For 21 days, physiological saline solution was treated to the control group and OVA was treated to the groups of OVA, OVA + dexamethasone (Dexa) and OVA + tyrosol groups, intraperitoneally and through inhalation. Additionally, 0.25 mg/kg Dexa was treated to the OVA + Dexa group and 20 mg/kg tyrosol to the OVA + tyrosol group by oral gavage. Serum, blood, bronchoalveolar lavage fluid (BALF) and lung tissues of the rats were examined. It was observed that MDA level decreased, GSH level and GPx activity increased, and there was no change in CAT activity in lung tissues of the tyrosol treatment groups. It was also observed that NF-κB, TNF-α, IL-4, IL-5, IL-13, IFN-γ and IgE levels decreased compared to the OVA group in lung tissue and serum samples except for serum NF-κB and IL-4. However, no effect on IL-1 ß level was observed. In addition, it was determined that tyrosol treatment increased the IL-10 level on both tissue samples. The results of the histopathological investigation of lung tissue showed that tyrosol significantly ameliorated OVA-induced histopathological lesions. Additionally, PAS staining showed that mucus hypersecretion was significantly reduced with the use of tyrosol. In addition, it was determined that the number of eosinophils decreased significantly in blood and BALF samples. The obtained results showed that tyrosol possessed antioxidant and anti-inflammatory features on OVA-induced rats and preserved tissue architecture.


Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Asthma/drug therapy , Phenylethyl Alcohol/analogs & derivatives , Allergens , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Asthma/immunology , Asthma/metabolism , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Catalase/metabolism , Cytokines/blood , Cytokines/immunology , Disease Models, Animal , Eosinophils/immunology , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Immunoglobulin E/blood , Leukocyte Count , Lung/drug effects , Lung/immunology , Lung/metabolism , Lung/pathology , NF-kappa B/immunology , Ovalbumin , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Rats, Wistar
12.
J Invest Surg ; 34(12): 1339-1347, 2021 Dec.
Article En | MEDLINE | ID: mdl-32781870

INTRODUCTION: The aim of this study was to investigate the effect of perineural dexamethasone against intraneural bupivacaine. MATERIAL AND METHODS: Rats were divided into 9 groups with 6 animals in each group; Group 1 (Intraneural saline 600 µL-2ndday), Group 2 (Intraneural saline 600 µL-7th day), Group 3 (Intraneural saline 600 µL + perineural dexamethasone 0.5 mg/kg-2nd day), Group 4 (Intraneural saline 600 µL + perineural dexamethasone 0.5 mg/kg-7th day), Group 5 (Intraneural bupivacaine 10 mg/kg-2nd day), Group 6 (Intranueral bupivacaine 10 mg/kg-7th day), Group 7 (Intraneural bupivacaine 10 mg/kg + perineurald exam ethasone 0.5 mg/kg-2nd day), Group 8 (Intraneural bupivacaine 10 mg/kg + perineural dexamethasone 0.5 mg/kg-7th day), Group 9 (Control group). At the end of the application period, histopathological and immunohistochemical examinations were analyzed. RESULTS AND CONCLUSION: It was observed that caspase 3 levels significantly increased in the 5th and 6th groups compared to the 1st and 2nd groups (p < 0.01). However, in the 7th and 8th groups, these levels were similar with 1st and 2nd groups. While a significant decrease in S 100 levels was detected in group 6 (p < 0.05), a significant increase occurred in Group 8 and reached the same levels as Group 2. According to histopathological evaluation, edema, vacuolization and myelin degeneration were significantly increased in groups 5 and 6 (p < 0.05). However, in the 8th group, the mentioned data showed a significant decrease and reached the same levels as group 2. As a result, perineural dexamethasone was found to have protective effects against intraneural bupivacaine induced sciatic nerve damage.


Anesthetics, Local , Bupivacaine , Dexamethasone/therapeutic use , Injections/adverse effects , Sciatic Nerve/injuries , Anesthetics, Local/adverse effects , Animals , Bupivacaine/adverse effects , Rats
13.
Andrologia ; 53(2): e13930, 2021 Mar.
Article En | MEDLINE | ID: mdl-33368464

One of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3 ) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3 -treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3  + ESC groups, and NF-κB increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3  + ESC group compared to AlCl3 group. It was also determined that AlCl3 -induced tissue injury was significantly prevented by ESC co-treatment.


Aluminum Compounds , Chlorides , Aluminum Chloride , Aluminum Compounds/toxicity , Animals , Antioxidants/pharmacology , Chlorides/toxicity , Humans , Male , Oxidative Stress , Rats , Rats, Wistar , Sperm Motility , Umbelliferones
14.
Naunyn Schmiedebergs Arch Pharmacol ; 393(9): 1691-1699, 2020 09.
Article En | MEDLINE | ID: mdl-32383030

The antioxidant and cardioprotective effects of oleuropein have been reported in several studies; however, its effect on ketamine cardiotoxicity has not been known yet. The aim of this study was to investigate the effects of oleuropein in ketamine-induced cardiotoxicity model in rats. A total of 28 male Wistar Albino rats were included in the study and they were randomly divided into four groups, each having seven rats. Group 1 (control): rats were given 1 mL of DMSO by oral gavage method for 7 days. Group 2 (ketamine): on the seventh day of the study, 60 mg/kg ketamine was administered intraperitoneally. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Group 3 (oleuropein): rats were given 200 mg/kg/day oleuropein by oral gavage method for 7 days. Group 4 (oleuropein + ketamine): rats were given 1 × 200 mg/kg oleuropein by oral gavage method for 7 days. Furthermore, 60 mg/kg ketamine was administered intraperitoneally on the seventh day of the experiment. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Serum cardiac marker (TnI, CK-MB and CK) levels were measured. Histopathological analysis was performed on a portion of the cardiac tissue. Cardiac tissue oxidative stress and antioxidant markers (MDA, GSH, GSH.Px and CAT), TNF-α, IL-6, NF-κB, COX-2 and Nrf-2 gene expressions, and protein conversion levels of related genes were determined. Data obtained showed that ketamine administration increased MDA (p < 0.001), TNF-α (p < 0.01), IL-6 (p < 0.01), COX-2 (p < 0.001) and NF-κB (p < 0.001) levels, as well as serum TnI (p < 0.001), CK-MB (p < 0.001) and CK (p < 0.01) levels whereas decreased GSH (p < 0.05) and Nrf-2 (p < 0.05) levels, as well as GSH-Px (p < 0.001) and CAT (p < 0.05) enzyme activities. Oleuropein administration was observed to decrease MDA, TNF-α, IL-6, COX-2, NF-κB, TnI, CK-MB and CK levels close to the control group and to increase GSH levels and GSH-Px and CAT enzyme activities close to the control group. This study showed that oleuropein administration reversed the increased oxidative stress and inflammation as a result of the use of ketamine and had protective effects on the heart.


Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Heart Diseases/prevention & control , Inflammation Mediators/metabolism , Iridoid Glucosides/pharmacology , Myocytes, Cardiac/drug effects , Oxidative Stress/drug effects , Animals , Cardiotoxicity , Disease Models, Animal , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Ketamine , Male , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Rats, Wistar , Signal Transduction
15.
Int J Vitam Nutr Res ; 90(3-4): 302-308, 2020 Jun.
Article En | MEDLINE | ID: mdl-30932786

This study aimed to investigate and compare hepatoprotective activity of Coriandrum sativum (Cs) and it is major component linalool (Ln) against experimentally induced hepatotoxicity in rats. Essential oil of Cs was isolated by hydrodistillation method and chemical composition was determined by GS-MS analysis. 42 male Wistar Albino rats were divited into 7 groups each containing 6. The experimental groups were designed as: Normal control group, 1 ml/kg CCl4 administirated group, 25 mg/kg Silymarin and CCl4 administirated group, 100 and 200 mg/kg Cs and CCl4 administirated groups, 100 and 200 mg/kg Ln and CCl4 administered groups. The protective activities were determined according to the results of liver biomarkers (AST, ALT, ALP), antioxidant parameters (GSH, GPx, CAT), lipid peroxidation (MDA) and histopathological examination. Linalool percentage of Cs was 81.6%. The groups treated with linalool (100 and 200 mg/kg) (p < 0.01) and coriander (200 mg/kg) (p < 0.05) had significantly reduced AST (262-375) and ALT (101-290) levels (U/L) compared to the CCl4 (600-622) group. The levels (nmol/g protein) of MDA (11-12) were significantly lower (p < 0.01), the levels of GSH (11-12) and the activities of CAT (23-24) were significantly higher (p < 0.01) in linalool groups (100 and 200 mg/kg) compared to the CCl4 (18-5-10 respectively) group. These results were also supported by histopathological findings and indicate that Cs and Ln shows hepatoprotective activity against liver damage. In this regard, evaluation of activities of major components are needed to compare to medicinal plants in experimental diseases models.


Acyclic Monoterpenes/chemistry , Antioxidants/chemistry , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Acyclic Monoterpenes/metabolism , Animals , Carbon Tetrachloride/chemistry , Lipid Peroxidation/physiology , Liver , Male , Plant Extracts , Rats , Rats, Wistar
16.
J Biochem Mol Toxicol ; 34(2): e22427, 2020 Feb.
Article En | MEDLINE | ID: mdl-31777137

The study aimed to examine the effects of nobiletin on the toxicity model induced with acetaminophen (APAP). For this purpose, 24 adult male rats were equally divided into four groups. The groups were the control group (group 1); dimethyl sulfoxide only, the APAP group (group 2) received a single dose of APAP 1000 mg/kg on the 10th day of experiment; the Nobiletin group (group 3), nobiletin (10 mg/kg) for 10 days; and the APAP + Nobiletin group (group 4), nobiletin (10 mg/kg) for 10 days with a single dose of APAP (1000 mg/kg) administered on the 10th day and the experiment ended after 48 hours. At the end of the study, a significant increase in malondialdehyde, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels and a significant decrease in glutathione levels, glutathione peroxidase activities and nuclear factor erythroid-derived 2-like 2 (Nrf-2) and heme oxygenase-1 (HO-1) expressions were observed with APAP application in liver and kidney tissues. Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, and creatinine levels were also significantly increased in the APAP group. However, nobiletin treatment in group 4 reversed oxidative stress and inflammatory and histopathological signs caused by APAP. It is concluded that nobiletin may be a beneficial substance that confers hepatorenal protection to APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms.


Acetaminophen/adverse effects , Acetaminophen/pharmacology , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Flavones/pharmacology , Kidney/drug effects , Liver/drug effects , Alanine Transaminase/blood , Animals , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/drug therapy , Creatinine/blood , Cytokines/metabolism , Flavones/therapeutic use , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Heme Oxygenase (Decyclizing)/metabolism , Kidney/metabolism , Kidney/pathology , Liver/metabolism , Liver/pathology , Male , Malondialdehyde/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Rats , Rats, Wistar , Urea/blood
17.
Andrologia ; 52(2): e13499, 2020 Mar.
Article En | MEDLINE | ID: mdl-31828839

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it is unavoidable. Tyrosol is present in olive oil and is known to have antioxidant effects. Therefore, the present study explores the toxic effects of aluminium chloride (AlCl3 ) and evaluates the possible protection by tyrosol in male rats. Testicular injury was induced by the administration of AlCl3 (34 mg kg-1  day-1 ). Rats were treated with either tyrosol (20 mg kg-1 day-1 ) or AlCl3 (34 mg kg-1 day-1 ). The experiment lasted for 10 weeks. Biochemical, histopathological and protein expression profiles were determined to decipher the role of tyrosol in protecting the cellular damage. Further, histomorphometric analyses of testes showed deranged architecture along with other noted abnormalities. AlCl3 group rats' testes showed decreased GSH levels, CAT activities, Nrf-2, HO-1, bcl-2 expressions and sperm motility whereas increased caspase-3 expressions, MDA levels, abnormal and dead/live sperm ratio. However, tyrosol treatment attenuated these changes. The present results demonstrate the beneficial role of tyrosol treatment in AlCl3 induced testicular toxicity alterations of rat.


Aluminum Chloride/toxicity , Antioxidants/therapeutic use , Infertility, Male/prevention & control , Phenylethyl Alcohol/analogs & derivatives , Testis/drug effects , Animals , Antioxidants/pharmacology , Drug Evaluation, Preclinical , Heme Oxygenase (Decyclizing)/metabolism , Infertility, Male/chemically induced , Infertility, Male/pathology , Male , NF-E2-Related Factor 2/metabolism , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Rats, Wistar , Testis/metabolism
18.
Inflammation ; 43(1): 336-346, 2020 Feb.
Article En | MEDLINE | ID: mdl-31705353

Ischemia-reperfusion injury is an organ failure caused by hypoxia and reperfusion, which is closely associated with oxidative stress and inflammation. In this study, we investigated whether nobiletin had protective effects on inflammatory parameters, oxidative damage, iNOS-eNOS expressions, and histopathological structure of renal tissue in rats with renal ischemia-reperfusion injury. For this purpose, 24 rats were divided into 4 groups: group 1 (Control), group 2 (Ischemia-Reperfusion-IR), group 3 (Nobiletin-10 mg/kg p.o.), group 4 (Nobiletin + IR). The study was continued for 7 days. At the end of the study, urea (p < 0.05), creatine (p < 0.05), MDA (p < 0.001), TNF-alpha (p < 0.001), IL-1 beta (p < 0.05), and IL-6 (p < 0.001) levels increased in the IR group; however, a significant decrease occurred in group 4 (Nobiletin + IR) and it reached the control group levels. In the IR group, GSH (p < 0.01) levels, and GSH.Px (p < 0.01) and CAT (p < 0.05) activities decreased whereas they increased significantly in group 4 (Nobiletin + IR) and reached the same levels as the control group. In histopathological analyses, destruction and increased iNOS-eNOS expressions in the IR group showed a significant decrease in group 4 (Nobiletin + IR). As a result, the application of nobiletin has shown that it has protective effects by reducing kidney damage caused by IR injury.


Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Flavones/pharmacology , Inflammation Mediators/metabolism , Kidney Diseases/prevention & control , Kidney/drug effects , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide Synthase Type II/metabolism , Reperfusion Injury/prevention & control , Animals , Disease Models, Animal , Kidney/enzymology , Kidney/pathology , Kidney Diseases/enzymology , Kidney Diseases/pathology , Male , Rats, Wistar , Reperfusion Injury/enzymology , Reperfusion Injury/pathology , Signal Transduction
20.
Inflammation ; 42(5): 1680-1691, 2019 Oct.
Article En | MEDLINE | ID: mdl-31115770

In this study, the effects of tyrosol were investigated in DSS-induced experimental ulcerative colitis model. For this purpose, rats were divided into five groups of seven rats in each: control group, colitis group (DSS-4%), tyrosol group (tyrosol 20 mg/kg), sulfasalazine (sulfasalazine+DSS 100 mg/kg), and treatment group (tyrosol+DSS 20 mg/kg). In the study, the active substances were administered to all animals for a period of 21 days. At the end of the study, malondialdehyde (MDA) levels increased (p < 0.001); GSH level (p < 0.05) along with GSH.Px (p < 0.01) and CAT (p < 0.001) activities decreased in the DSS-induced colitis group. However, with the administration of tyrosol, MDA and GSH levels along with GSH.Px and CAT activities came to the same levels as the control group. In the colitis group, an increase occurred in IL-6, COX-2, and NF-κB parameters, which created a significant difference compared to the control group (p < 0.001). Similarly, TNF-α levels also significantly increased with the administration of DSS (p < 0.05) which created a significant difference compared to the control group, while there was no difference among the other groups. As for the Nrf-2 data, it decreased with the administration of DSS which created a significant difference compared to the control group (p < 0.05), while there was no difference in other groups. In the colitis-induced group, IL-6, COX-2, and NF-κB gene expression levels also similarly increased but returned to the normal levels with the administration of tyrosol. In the histopathological scoring, the negativity that increased with the administration of DSS returned to the normal levels with the administration of tyrosol+DSS. In conclusion, according to the data obtained, tyrosol fixed the destruction picture in the DSS-induced colitis model, giving rise to thought that it has a protective effect.


Antioxidants/therapeutic use , Colitis, Ulcerative/drug therapy , Phenylethyl Alcohol/analogs & derivatives , Protective Agents/therapeutic use , Animals , Antioxidants/pharmacology , Colitis, Ulcerative/chemically induced , Cyclooxygenase 2/metabolism , Dextran Sulfate , Glutathione/drug effects , Glutathione/metabolism , Malondialdehyde/metabolism , NF-kappa B/metabolism , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Protective Agents/pharmacology , Rats , Tumor Necrosis Factor-alpha/metabolism
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