Metformin reduces ovarian ischemia reperfusion injury in rats by improving oxidative/nitrosative stress

Demır, Mustafa; Yılmaz, Bülent; Kalyoncu, Şenol; Tuncer, Meltem; Bozdağ, Zehra; İnce, Onur; Bozdayı, Mehmet Akif; Ulusal, Hasan; Taysı, Seyithan

doi:10.1016/j.tjog.2020.10.004

Cited by 14 publications

(8 citation statements)

References 30 publications

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“…Metformin is the first-line drug for the treatment of type 2 diabetes, and several studies have demonstrated that it plays a crucial role in ischemia-reperfusion injury in different organs such as the heart, gut, brain, kidney, bladder, testis, ovary, and liver [ 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. Generally, metformin inhibits apoptosis and autophagy and reduces oxidative stress, mainly by regulating the signal transduction pathways [ 98 , 99 ].…”

Section: Inhibition Of Pyroptosis By Drugs and Improved Mirimentioning

confidence: 99%

Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury

Yang

Zhang

et al. 2022

Cells

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Myocardial ischemia-reperfusion injury (MIRI) results in the aggravation of myocardial injury caused by rapid recanalization of the ischemic myocardium. In the past few years, there is a growing interest in investigating the complex pathophysiological mechanism of MIRI for the identification of effective targets and drugs to alleviate MIRI. Currently, pyroptosis, a type of inflammatory programmed death, has received greater attention. It is involved in the MIRI development in combination with other mechanisms of MIRI, such as oxidative stress, calcium overload, necroptosis, and apoptosis, thereby forming an intertwined association between different pathways that affect MIRI by regulating common pathway molecules. This review describes the pyroptosis mechanism in MIRI and its relationship with other mechanisms, and also highlights non-coding RNAs and non-cardiomyocytes as regulators of cardiomyocyte pyroptosis by mediating associated pathways or proteins to participate in the initiation and development of MIRI. The research progress on novel small molecule drugs, clinical drugs, traditional Chinese medicine, etc. for regulating pyroptosis can play a crucial role in effective MIRI alleviation. When compared to research on other mature mechanisms, the research studies on pyroptosis in MIRI are inadequate. Although many related protective drugs have been identified, these drugs generally lack clinical applications. It is necessary to further explore and verify these drugs to expand their applications in clinical setting. Early inhibition of MIRI by targeted regulation of pyroptosis is a key concern that needs to be addressed in future studies.

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Section: Inhibition Of Pyroptosis By Drugs and Improved Mirimentioning

confidence: 99%

Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury

Yang

Zhang

et al. 2022

Cells

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“…Some studies have confirmed that the massive accumulation of ROS and other mitochondrial oxidative stress-induced functional disorders is the early signaling of cisplatin-induced pathological events, such as inflammatory response and several apoptotic signal pathways mediated by caspases and mitogen-activated protein kinases (MAPKs) [40][41][42][43][44][45]. Meanwhile, researches show that other stress like nitrosative stress produces a toxic role in cisplatin-induced nephrotoxicity by another free radical, RNS [46,47], and also indicate that nitrosative stress and oxidative stress form a quantity of steps in the mechanism of cell damage together [39,48,49]. However, this review mainly focuses on oxidative stress and ROS and discusses the mechanism of cisplatin-induced oxidative stress response that contributes to nephrotoxicity.…”

Section: Accumulation Of Ros Is the Upstreammentioning

confidence: 99%

Protective Effect of Natural Antioxidants on Reducing Cisplatin-Induced Nephrotoxicity

et al. 2022

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The clinical application of cisplatin is limited by its adverse events, of which nephrotoxicity is the most commonly observed. In a cisplatin-induced pathological response, oxidative stress is one of the upstream reactions which inflicts different degrees of damages to the intracellular material components. Reactive oxygen species (ROS) are also one of the early signaling molecules that subsequently undergo a series of pathological reactions, such as apoptosis and necrosis. This review summarizes the mechanism of intracellular ROS generation induced by cisplatin, mainly from the consumption of endogenous antioxidants, destruction of antioxidant enzymes, induction of mitochondrial crosstalk between the endoplasmic reticulum by ROS and Ca2+, and destruction of the cytochrome P450 (CYP) system in the endoplasmic reticulum, all of which result in excessive accumulation of intracellular ROS and oxidative stress. In addition, studies demonstrated that natural antioxidants can protect against the cisplatin-induced nephrotoxicity, by reducing or even eliminating excess free radicals and also affecting other nonredox pathways. Therefore, this review on the one hand provides theoretical support for the research and clinical application of natural antioxidants and on the other hand provides a new entry point for the detailed mechanism of cisplatin nephrotoxicity, which may lay a solid foundation for the future clinical use of cisplatin.

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“…Ovarian torsion is an emergent surgical condition that is more common in women of childbearing age. Ovarian torsion is characterized by a twist of the ovary around its supporting ligaments so that it causes obstruction of the ovarian vessels and eventually ovarian ischemia, necrosis, and irreversible damage (Demir et al 2021). Although detorsion of the ovary is the major line of treatment, it is associated with excess of reactive oxygen species (ROS) production, which worsens the condition.…”

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confidence: 99%

“…In several animal models of IR injuries, leptin decreased the severity of these injuries via its antioxidant, anti-apoptotic, and anti-inflammatory activities (Sarsu et al 2015;Zhang et al 2019;Ragy and RaMzy 2021). There are many studies demonstrating that agents with antioxidant or anti-inflammatory activities may be beneficial in reducing ovarian IR injury (Colak et al 2020;Ali et al 2021;Demir et al 2021). Thus, the current study was designed to investigate the probable protective effect of two doses of leptin (10 or 100 µg/kg body weight) in a rat model of ovarian IR injury and explore the underlying mechanisms that could be involved.…”

mentioning

confidence: 99%

Leptin alleviated ovarian ischemia-reperfusion injury in rats via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways

Abdel-Hamid

Maqsoud

Toni

et al. 2023

Endocrine Regulations

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Objective. Ovarian torsion is a gynecological emergency that occurs mostly during the female reproductive years due to ovarian masses or surgical manipulation. This work aims to explore the probable protective effect of leptin on rat ovaries due to ischemia-reperfusion (IR) injury. Methods. Wistar albino rats were divided into four groups: 1) control group; 2) ovarian IR group (OVIR); 3) leptin group I [OVIR + leptin (10 µg/kg body weight, b.w.)]; and 4) leptin group II (OVIR + leptin (100 µg/kg b.w.)]. Serum levels of estradiol and anti-Mullerian hormone (AMH) were measured. Levels of oxidative stress and inflammatory markers in ovarian tissue were determined along with the expression of sirtuin 1 (Sirt1), nuclear erythroid factor-2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor kappa (NF-κB), toll like receptor-4 (TLR4), and caspase-3. Results. Serum estradiol and AMH levels were decreased with increased expression of COX-2, TLR4, caspase-3, and NF-κB and decreased expression of Sirt1and Nrf2 in ovary of the OVIR group, which were improved by exogenous administration of both leptin doses. Conclusion. Leptin administration dose-dependently reduced the severity of OVIR injury via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways. Thus, leptin may be used as an adjuvant measure to prevent ovarian damage and improve the outcomes. However, clinical studies are needed to evaluate these results in humans.

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Metformin reduces ovarian ischemia reperfusion injury in rats by improving oxidative/nitrosative stress

Cited by 14 publications

References 30 publications

Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury

Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury

Protective Effect of Natural Antioxidants on Reducing Cisplatin-Induced Nephrotoxicity

Leptin alleviated ovarian ischemia-reperfusion injury in rats via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways

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