The effects of amiodarone in ovarian injury due to oxidative stress and inflammation caused by ischemia-reperfusion.

OBJECTIVE: Ovarian ischemia constitutes 2-3% of all gynecological emergencies. New-generation therapeutic agents need to be discovered, in addition to invasive interventions capable of reducing the risk of potential ovarian ischemia to a minimum and protecting against potential adverse outcomes. AIMS: To investigate the effects of amiodarone (AMD) on ischemia-reperfusion-induced oxidative stress and inflammation-induced ovarian damage. METHODS: The control group, received intraperitoneal (i.p.) injection of saline solution. The ischemia group (I-Group), was subjected to ischemia-induced injury without drug administration. The ischemia + AMD (50 mg/kg) group was subjected to ischemia injury and also received i.p. 50 mg/kg AMD prior to induction of ovarian ischemia. The ischemia-reperfusion (I/R group) was exposed to ischemia and reperfusion-induced injury without drug administration. The I/R + AMD (50 mg/kg) group underwent I/R injury together with i.p. administration of 50 mg/kg AMD prior to induction of ovarian I/R. The Sham + AMD group received intraperitoneal (i.p.) injection of 50 mg/kg AMD alone. In this study performed thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin 1 Beta (IL-1ß), interleukin 6 (IL-6), toll-like receptor 4 (TLR4) and nuclear factor-kappa B(NF-κß). RESULTS: Increased oxidative stress and inflammation as a result of ovarian I and I/R application activated the cascade. AMD was not sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-kß, which were up-regulated by triggering oxidative stress and inflammation, were not regressed by the effects of AMD. CONCLUSIONS: AMD, used as an antiarrhythmic agent, was found to be insufficient, despite its antioxidant and anti-inflammatory properties, to reduce the experimentally induced ovarian tissue damage.

The protective effects of trimetazidine against ovary ischemia-reperfusion injury via the TLR4/Nf-kB signal pathway.

Late diagnosis and treatment of ovarian ischemia can lead to worsening of ischemia, irreversible damage to ovarian functions and infertility. In this process, there is no approved medical treatment that can reduce the negative effects of ischemia and contribute positively to ovarian functions during reperfusion after detorsion. Rats were randomly assigned into one of six groups of eight animals each. The groups were designed as follows: The control group, The ischemia(I) group, The Ischemia + Trimetazidine (I + TMZ) (20 mg/kg) group, and The ischemia-reperfusion group (I/R). The Ischemia-Reperfusion + Trimetazidine (I/R + TMZ) (20 mg/kg) group, and The Sham + Trimetazidine (Sham + TMZ) (20 mg/kg) group. In this study performed thiobarbituric acid reactive substances (TBARS), total thiol (-SH), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), toll-like receptor 4 (TLR4), and nuclear factor-kappa B(NF-κß). Increased oxidative stress and inflammation were as a result of ovarian I and I/R application. Trimetazidine (TMZ), was sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-κß, which were upregulated by oxidative stress and inflammation, were regressed by TMZ. TMZ should be considered as a potential therapeutic agent in addition to surgery in the clinical treatment of ovarian torsion.

The effects of vitamin B12 on the TLR-4/NF-κB signaling pathway in ovarian ischemia-reperfusion injury-related inflammation.

Ovarian ischemia is a gynecological emergency case that occurs as a result of ovarian torsion. Oxidative stress and inflammation play central roles in the development of ischemia/reperfusion injuries. We investigated the effects of Vitamin B12, thought to possess antioxidant characteristics on oxidative stress and the toll-like receptor 4 (TLR-4)/nuclear factorkappa B (NF-κB) signaling pathway in the ovaries during ischemia-reperfusion. Forty-eight rats were randomly assigned into six groups and the groups are designed as follows: Control (C), Ischemia (I), Ischemia + Vitamin B12 (I + B12), Ischemia-Reperfusion (I/R), I/R + Vitamin B12 (I/R + B12) and Sham + Vitamin B12. Vitamin B12 was administered at a dose of 400 mcg/kg via the i.p. route once daily for three days before I/R procedure. Tissue interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and malondialdehyde (MDA) levels in ovarian tissue increased following I/R, while glutathione (GSH) levels decreased. Moreover, extensive congestion, edema, hemorrhage and defective follicle were observed. Both NF-κB and TLR-4 expression levels also increased in the group exposed to I/R. While GSH levels increased, IL-1ß, IL-6, MDA, NF-κB and TLR-4 levels decreased with Vitamin B12 treatment. In addition, ovarian tissue without edema, mild congestion, and normal-appearing follicles were observed following Vitamin B12 administration. The findings showed that I/R in ovarian tissue resulted in significant tissue damage by increasing oxidative stress and inflammation. However, Vitamin B12 application was effective and alternative agent in reducing injury deriving from inflammation and oxidative stress developing in association with I/R in ovarian tissue.

Melatonin protects myocardium from ischemia-reperfusion injury in hypertensive rats: role of myeloperoxidase activity.

Increased levels of reactive oxygen species, alterations in nitric oxide synthesis, and increased migration of neutrophils to the ischemic tissue play an important role in the pathophysiology of myocardial ischemia-reperfusion (IR) injury. In this study, we have evaluated the effects of melatonin on myeloperoxidase (MPO) activity, tissue glutathione (GSH), lipid peroxidation levels, and blood pressure in L-NAME-induced hypertensive rats with or without IR. NOS inhibitor L-NAME was administrated before inducing cardiac ischemia for 15 days intraperitoneally. For the cardiac ischemia, the left coronary artery was ligated for 30 min, and reperfusion was performed for 120 min after the ischemia. L-NAME treatment in non-ischemic animals increased blood pressure and lipid peroxidation, and decreased glutathione level in myocardial tissue significantly as compared with non-L-NAME-treated animals. Melatonin reversed L-NAME-induced blood pressure elevation and oxidative changes. Cardiac IR increased MDA levels and MPO activity and decreased GSH levels as compared with non-ischemic animals. L-NAME treatment did not change in IR-induced MDA and GSH levels as compared with ischemic control animals. However, MPO activity was significantly higher than control ischemic animals. MDA levels and MPO activity resulting from ischemic injury in melatonin-treated animals were significantly less than L-NAME-treated animals. Taken together-the ischemic and non-ischemic control and melatonin-treated animals-this study shows that neutrophil migration plays an important role on the development of ischemic injury in hypertensive rats.

Nitric oxide synthase inhibition in rats: melatonin reduces blood pressure and ischemia/reperfusion-induced infarct size.

Reduction in the synthesis or bioavailability of nitric oxide plays a significant role in the development of myocardial infarction and hypertension. Numerous studies suggest that melatonin reduces blood pressure (BP) and ischemia/reperfusion (I/R) injury in rats. The effects of melatonin on the BP and I/R-induced cardiac infarct size in L-NAME-induced hypertensive rats remains unknown. This study was designed to investigate the effects of melatonin on BP and the I/R-induced infarct size in chronic nitric oxide synthase inhibited rats by L-NAME. Rats received L-NAME for 15 days to produce hypertension and melatonin the last 5 days before I/R studies. To produce cardiac damage, the left coronary artery was occluded for 30 min, followed by 120 min reperfusion. L-NAME led to a significant increase in BP. Melatonin administration (10 mg/kg) to L-NAME treated rats significantly reduced BP and infarct size. Also, melatonin attenuated the mortality resulting from I/R, but this was not statistically significant. Melatonin administration would seem important to reduce BP and infarct size resulting from I/R in L-NAME-induced hypertensive rats.

[Myocardial ischemia-reperfusion injury and melatonin]. / Miyokardiyal iskemi-reperfüzyon hasari ve melatonin.

It is believed that myocardial ischemia-reperfusion injury is related to increased free radical generated and intracellular calcium overload especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger, antioxidant and can inhibit the intracellular calcium overload. In this review, we have summarized the fundamental of cardiac ischemia-reperfusion injury and the effects of melatonin on myocardial damage that related to cardiac ischemia-reperfusion injury. The total antioxidant capacity of human serum is related to melatonin levels. Incidence of sudden cardiac death is high in the morning hours. It has been shown that melatonin levels are significantly low at these times and patients with coronary heart disease have lower than normal individuals. These findings thought that melatonin would be valuable to test in clinical trials for prevention of possible ischemia-reperfusion-induced injury, especially life threatening arrhythmias and infarct size, effecting life quality, associated with thrombolysis, angioplasty, coronary artery spasm or coronary bypass surgery.

Melatonin attenuates renal ischemia-reperfusion injury in nitric oxide synthase inhibited rats.

Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.48+/-0.2mg/l serum) than in the control group (2.69+/-0.2mg/l serum). L-NAME (40 mgkg(-1) for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.