Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model

Abstract

Introduction Etanercept has been widely used in autoimmune diseases for blocking tumor necrosis factor α (TNF-α), which is an inflammatory cytokine. The anti-apoptotic and anti-inflammatory effects of etanercept against ischemia/reperfusion (I/R) injury have been shown for several tissues in rat studies, but to the best of our knowledge, there are no reports on its protective effects following similar injury in ovarian tissue. The aim of this study was to investigate whether etanercept has beneficial effects on ovarian I/R injury, as well as on ovarian reserve. Material and methods Twenty-four rats were randomly divided into four groups ( n = 6/group): sham (laparotomy only); sham + etanercept; I/R; and I/R + etanercept. Ischemia was induced for 3 h by twisting the ovary, and 24 h after detorsion the ovarian tissues were collected to evaluate histopathologic changes, glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) concentrations for oxidative stress, 8-hydroxy-2′-deoxyguanosine (8-OHdG) for DNA damage, caspase-3 activity for apoptosis and ovarian follicle counts. To measure anti-Mullerian hormone (AMH), serum samples were drawn before and after surgery. Results Tissue GSH and SOD levels were significantly higher, while MDA and MPO levels were significantly lower in the I/R + etanercept group than in the I/R group ( p < 0.05, p < 0.01, respectively). Tissue 8-OHdG and caspase-3 activity were significantly lower in the I/R+etanercept group than in the I/R group ( p < 0.05, p < 0.01, respectively). Preoperative and postoperative AMH levels were compared and there was a significant reduction in the I/R and I/R + etanercept groups ( p < 0.001, p < 0.001). The reduction of AMH in the I/R + etanercept group was significantly lower than in the I/R group. The primordial, preantral and small antral follicle numbers were also significantly higher in the I/R + etanercept group compared to the I/R group ( p < 0.001 , p < 0.001, p < 0.005, respectively). Conclusions Etanercept attenuated inflammation and related oxidative stress and also helped to preserve ovarian reserve following ovarian I/R damage.

Protective effects of nebivolol on ovarian ischemia–reperfusion injury in rat

“…29 Previous studies have demonstrated that I/R injury aggravates oxidant injury in the ovarian tissue, causing significantly reduced GSH levels; which eventually contribute to cellular injury. 12,30 A similar study by Yayla et al demonstrated a significant reduction in the GSH level in the ovarian tissue after I/R in the case group. 31 We observed similarly reduced GSH levels in the I and I/R groups in our study parallel to the results of previous studies discussed above.…”

“…10 Previous studies identified many agents with antioxidant effects, preventing oxidative stress caused by ischemia and reperfusion (I/R) injury in the ovary. 11,12 In addition, the levels of tumor necrosis factor-alpha (TNF-α) and other proinflammatory cytokines increase in reperfusion injury; suggesting that anti-inflammatory agents can be involved more effectively in the prevention of ischemic damage compared to antioxidants. From this point of view, nebivolol (NEB) can be a promising therapeutic agent as it has been displayed to have antiinflammatory and anti-apoptotic effects besides its antioxidant properties.…”

“…In contrast, glutathione (GSH) protects the tissue against reactive oxygen species (ROS), preventing tissue damage and helping the maintenance of the balance between oxidants and antioxidants 10 . Previous studies identified many agents with antioxidant effects, preventing oxidative stress caused by ischemia and reperfusion (I/R) injury in the ovary 11,12 . In addition, the levels of tumor necrosis factor‐alpha (TNF‐α) and other proinflammatory cytokines increase in reperfusion injury; suggesting that anti‐inflammatory agents can be involved more effectively in the prevention of ischemic damage compared to antioxidants.…”

Kannabinoid Tip 2 Reseptör Agonistinin Sıçanlarda Over İskemi/reperfüzyon Hasarına Karşı Koruyucu Etkisi

“…26 In ovarian I/R injury, all or part of the blood circulation may be temporarily blocked in surgical interventions, especially caesarean section, or in traumatic events. 27 Although ovarian damage has occurred during ischemia, it has been shown in previous studies that the main damage takes place during reperfusion. 28 In line with the results of previous studies, the results of this study show that reperfusion increases the harmful eff ects of ischemic damage because of migration of active neutrophils and ROS formation.…”

mRNA-103 inhibition attenuates autophagy and inflammation in myocardial infarction by regulating the TLR4 pathway

“…Oxidative stress reduction has been reported to prevent injury of myocardial tissues [21], and the results of our study also show that treatment with mRNA-103 inhibitor reduces the increased level of oxidative stress. Myocardial infarction occurs due to hypoxia to the myocardial tissues, which activates the apoptosis pathway and increases the apoptosis of myocardiocytes [22][23][24][25]. Apoptosis of myocardiocytes contributes to the degeneration of myocardial tissues, which leads to MI.…”