ABSTRACT
BACKGROUND: Ovarian ischemia and reperfusion can lead to serious and irreversible health problems. OBJECTIVES: The aim of this study is to investigate the protective effect of agomelatine against ovarian ischemia/ /reperfusion injury in rats using biochemical methods. MATERIAL AND METHODS: Thirty female rats were divided into three groups (the number of animals in each group = 10), a control group in which ischemia/reperfusion was established (IRC), an ischemia/reperfusion + agomelatine (IRA) group and a healthy group given a sham operation (SG). Total glutathione (tGSH) and malondialdehyde (MDA) levels and glutathione peroxidase. RESULTS: Biochemical results revealed MDA levels of 19.1 ± 2.03, 5.8 ± 1.5 and 5.5 ± 1.4 µmol/g protein in ovarian tissue in the IRC, IRA and SG groups, respectively. MPO activity in the IRC, IRA and SG groups was 7.87 ± 2.7, 4.0 ± 2.0 and 3.0 ± 1.0 U/g protein, respectively. tGSH levels were 1.87 ± 1.13, 4.37 ± 1.4 and 5.87 ± 1.64 nmol/g protein, respectively. GPx activity in the IRC, IRA and SG groups was 7.37 ± 1.68, 18.6 ± 3 and 17.75 ± 3.2 U/g protein, and SOD activity 31.1 ± 2.9, 45.3 ± 3.7 and 54 ± 4.2 U/g protein, respectively. The level of 8-OH/ /Gua, a product of DNA damage, was 2.18 ± 0.2 pmol/L in the IRC group, 1.28 ± 0.2 pmol/L in the IRA group and 0.93 ± 0.01 pmol/L in the SG group. CONCLUSIONS: Agomelatine prevented ovarian ischemia/reperfusion injury.
ABSTRACT
BACKGROUND: Nimesulide is a pharmacological agent and selective COX-2 inhibitor. It has anti-inflammatory, analgesic and antipyretic properties. The purpose of this study was to investigate the effect of nimesulide on oxidant/antioxidant, DNA mutation and COX-1/COX-2 activities in rat liver tissue with induced ischemia/reperfusion (I/R). METHODS: Before the experiment, rats were divided into four groups; liver ischemia/reperfusion (LIR), 50mg/kg nimesulide+liver ischemia/reperfusion (NLIR50), 100mg/kg nimesulide+liver ischemia/reperfusion (NLIR100) and a control group to be given a sham operation (SG). Malondialdehyde (MDA), total glutathione (GSH) levels and myeloperoxidase (MPO), COX-1/COX-2 enzyme activities and DNA damage product level results from liver tissues and serum AST and ALT levels were determined. The data obtained were compared with the results from the liver ischemia/reperfusion and sham operation groups. RESULTS: MDA levels, MPO and COX-2 activities and products of DNA injury were significantly lower in the groups given nimesulide, and particularly the NLIR100 group, compared to the LIR group (p<0.05), while tGSH levels were significantly higher (p<0.05). There was no significant difference between the NLIR50 and NLIR100 groups and the LIR group in terms of COX-1 levels (p>0.05). AST and ALT levels were significantly lower in the other groups compared to the LIR group (p<0.05). CONCLUSIONS: Nimesulide at 100mg/kg prevented oxidative liver damage induced with I/R significantly better than at a dose of 50mg/kg. These experimental findings indicate that nimesulide may be useful in the treatment of hepatic I/R damage.
Subject(s)
Antioxidants/metabolism , Cyclooxygenase 1/metabolism , Cyclooxygenase 2 Inhibitors/therapeutic use , DNA Damage , Lipid Peroxidation/drug effects , Liver/blood supply , Reperfusion Injury/prevention & control , Sulfonamides/therapeutic use , Animals , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/administration & dosage , Cyclooxygenase 2 Inhibitors/pharmacology , DNA Damage/genetics , Dose-Response Relationship, Drug , Liver/drug effects , Liver/enzymology , Liver Function Tests , Male , Mutation , Rats, Wistar , Reperfusion Injury/enzymology , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Sulfonamides/administration & dosage , Sulfonamides/pharmacologyABSTRACT
AIM: This study is a biochemical investigation of the effect of etoricoxib, a selective cyclooxygenase (COX)-2 inhibitor, on ischemia/reperfusion (I/R) injury experimentally induced in rat ovaries. METHODS: Experimental animals were divided into four groups: (i) ovarian ischemia/reperfusion (IRG); (ii) 30 mg/kg etoricoxib + ovarian ischemia/reperfusion (EIRG-30); (iii) 60 mg/kg etoricoxib + ovarian ischemia/reperfusion (EIRG-60); and (iv) a sham operation (SG) control group. RESULTS: The results showed levels of malondialdehyde in the IRG, EIRG-30, EIRG-60 and SG group ovarian tissue of 20.2 ± 3.4, 11.2 ± 3.2, 5.5 ± 1.9 and 3.8 ± 1.5 µmol/g protein, respectively. Myeloperoxidase activity for these groups was 24.2 ± 6.7, 13 ± 2.4, 4 ± 1.8 and 3.5 ± 1.9 U/g protein, and total glutathione levels were 1.6 ± 0.8, 4.5 ± 1.9, 6.5 ± 1.9 and 7.5 ± 2.4 nmol/g protein, respectively. COX-1 activity in IRG, EIRG-30, EIRG-60 and SG group rat ovarian tissue was 5.0 ± 2.8, 12.2 ± 2.4, 16.7 ± 2.8 and 17.5 ± 4.7 U/mg protein, and COX-2 activity was 18.3 ± 2.7, 3.5 ± 1, 1.8 ± 0.7 and 0.7 ± 0.3 U/mg protein, respectively. CONCLUSION: Etoricoxib prevented oxidative damage induced with I/R in rat ovarian tissue. This property of etoricoxib suggests that it can be clinically beneficial in the prevention of damage that may arise with reperfusion by detorsion for the protection of the ovaries against torsion.
Subject(s)
Cyclooxygenase 2 Inhibitors/therapeutic use , Ovary/blood supply , Pyridines/therapeutic use , Reperfusion Injury/prevention & control , Sulfones/therapeutic use , Animals , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/pharmacology , Etoricoxib , Female , Glutathione/metabolism , Malondialdehyde/metabolism , Membrane Proteins/metabolism , Ovary/drug effects , Ovary/metabolism , Peroxidase/metabolism , Pyridines/pharmacology , Rats, Wistar , Sulfones/pharmacologyABSTRACT
This study investigated the effect of thiamine pyrophosphate on oxidative damage associated with cardiotoxicity caused by cisplatin (CIS), an antineoplastic agent, in rats, and compared this with thiamine. Animals used in the study were divided into four groups of 6 rats each. These represented a control group receiving 5 mg/kg of CIS, study groups receiving 20 mg/kg of thiamine pyrophosphate plus 5 mg/kg of cisplatin (CTPG) or 20 mg/kg of thiamine plus 5 mg/kg of cisplatin and a healthy (H) group. All doses were administered intraperitoneally once a day for 14 days. Malondialdehyde, total glutathione and products of DNA injury results were similar in the CTPG and H groups (p > 0.05). Creatinine kinase, creatine kinase MB and troponin 1 levels were similar in the CTPG and H groups (p > 0.05). Thiamine pyrophosphate prevented CIS-associated oxidative stress and heart injury, whereas thiamine did not prevent these.
Subject(s)
Cardiotoxicity/prevention & control , Cisplatin/toxicity , Thiamine Pyrophosphate/pharmacology , Thiamine/pharmacology , Animals , Antineoplastic Agents/toxicity , Cardiotoxicity/etiology , DNA Damage/drug effects , Glutathione/metabolism , Injections, Intraperitoneal , Male , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Rats , Rats, Wistar , Vitamin B Complex/pharmacologyABSTRACT
In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. For these experiments, rats were fasted for 24 h. Different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats, followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test, or 50% ethanol for the ethanol-induced test. Results have shown that at all of the doses used (50, 100 and 200 mg/kg), metyrosine had significant anti-ulcerative effects in both indomethacin and ethanol-induced ulcer tests. Metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. In addition, to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (COX) activity in inflammatory tissue (rat paw). The results showed that all doses of metyrosine significantly inhibited high COX-2 activity. The degree of COX-2 inhibition correlated with the increase in anti-inflammatory activity. In conclusion, we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of COX-2 enzymes by metyrosine. We also found that adrenalin levels are reduced upon metyrosine treatment, which may be the cause of the observed gastro-protective effects of this compound.
