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Artigo em Inglês | 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.

Inflammation ; 43(1): 336-346, 2020 Feb.
Artigo em Inglês | 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.

Andrologia ; 52(2): e13499, 2020 Mar.
Artigo em Inglês | 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.

J Biochem Mol Toxicol ; 34(2): e22427, 2020 Feb.
Artigo em Inglês | 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.

Acetaminofen/efeitos adversos , Acetaminofen/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonas/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Creatinina/sangue , Citocinas/metabolismo , Flavonas/uso terapêutico , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Ureia/sangue
Inflammation ; 42(5): 1680-1691, 2019 Oct.
Artigo em Inglês | 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.

Antioxidantes/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Substâncias Protetoras/uso terapêutico , Animais , Antioxidantes/farmacologia , Colite Ulcerativa/induzido quimicamente , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Substâncias Protetoras/farmacologia , Ratos , Fator de Necrose Tumoral alfa/metabolismo
Arch Physiol Biochem ; 125(5): 396-403, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29799283


In this study, we have investigated the effects of different doses of thymol (T) and carvacrol (C) on sperm quality oxidative stress and antioxidant system. For this purpose, 49 rats were divided into seven groups (7 rats in each group): 1st Group (control); 2nd Group T-10 (thymol 10 mg/kg), 3rd Group T-20 (thymol 20 mg/kg), 4th Group C-10 (carvacrol 10 mg/kg), 5th Group C-20 (carvacrol 20 mg/kg), 6th Group T + C-10 (thymol 10 mg/kg + carvacrol 10 mg/kg) and 7th Group T + C-20 (thymol 20 mg/kg + carvacrol 20 mg/kg). The duration of the experiment was 10 weeks for all animals. During the study, sperm quality parameters (motility, concentration, abnormal spermatozoa and live-dead sperm ratio), biochemical parameters [malondialdehyde (MDA), reduced glutathione(GSH), glutathione peroxidase (GSH-Px), catalase (CAT), AST, ALT, GGT, urea and creatinine] were analysed, and histopathological examination was performed. The study results showed that monotherapies of thymol and carvacrol significantly decreased MDA levels in testicles, liver and kidney tissues compared to the control group (p < .001). GSH levels increased only with the thymol administration and GSH-Px and catalase activity increased only with the carvacrol administration compared to the control group (p < .05). The combined administration of these two agents did not cause any significant change in any parameter. Regarding the sperm quality parameters, only the spermatozoa concentration and motility increased significantly in the thymol and carvacrol groups compared to the control group (p < .01). However, these parameters decreased in the 7th Group (T + C-20) compared to the control group (p < .001). Considering the dead sperm ratio decreased significantly in the 2nd (T-10), 3rd (T-20), 4th (C-10), 5th (C-20) and 6th Group (T + C-10) compared to the control group (p < .001). In respect of spermatozoon anomaly, there was a significant decrease in thymol and carvacrol monotherapy groups. The histopathological analysis of the testicle, liver and kidney tissues of the animals showed no difference between the groups. In conclusion, we have determined that thymol and carvacrol administration decreased the oxidative damage and increased the antioxidant levels and improved the sperm quality parameters. However, the combined use of these two active ingredients had a limited therapeutic effect on the mentioned parameters.

Antioxidantes/metabolismo , Monoterpenos/farmacologia , Oxidantes/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Timol/farmacologia , Animais , Cimenos , Relação Dose-Resposta a Droga , Masculino , Ratos , Espermatozoides/citologia