Leptin and curcumin affect renal ischemia-reperfusion injury via modulation of P65 and Bax genes expression

Ragy, Merhan; Ramzy, Maggie M.

doi:10.15407/ubj93.01.051

Cited by 2 publications

(5 citation statements)

References 46 publications

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“…Importantly, our results do not contradict data from several studies that link systemic leptin preconditioning prior to IR injury with tissue protection [16‒19]. These reports, which utilized leptin via a fundamentally different delivery method and timing of administration than our studies, show that systemic preconditioning pre-IR injury offers tissue protection.…”

Section: Discussionsupporting

confidence: 68%

“…The pleiotropic functions of leptin, which include many systemic effects, greatly complicate the study of its local function using conventional genetic and chemical experimental strategies. For instance, several studies in rodents demonstrated that systemic leptin pretreatment prior to inducing renal IR injury provides nephroprotection against acute kidney injury [15][16][17][18]. Preconditioning mechanisms have been suggested to underlie this effect including decreased p53 and TNF-α levels.…”

Section: Introductionmentioning

confidence: 99%

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Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

Jonas¹,

Simon²,

Gilburd³

et al. 2023

Am J Nephrol

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Introduction: Renal ischemia and reperfusion (IR) injury introduces cellular stress and is the main cause of acute kidney damage. Renal cells exposed to noxious stress induce the expression of the pleiotropic hormone leptin. As we have previously revealed a deleterious stress-related role for leptin expression, these results suggested that leptin is also involved in pathological renal remodeling. The systemic functions of leptin preclude the study of its local effects using conventional approaches. We have therefore designed a method to locally perturb leptin activity in specific tissues without affecting its systemic levels. This study explores whether local anti-leptin strategy is renoprotective in a post-IR porcine kidney model. Methods: We induced renal IR injury in pigs by exposing kidneys to ischemia and revascularization. Upon reperfusion, kidneys instantly received an intra-arterial bolus of either a leptin antagonist (LepA) or saline solution. Peripheral blood was sampled to assess systemic leptin, IL-6, creatinine, and BUN levels, and postoperative tissue samples were analyzed by hematoxylin and eosin histochemistry and immunohistochemistry. Results: Histology of IR/saline kidneys exhibited extensive necrosis of proximal tubular epithelial cells, as well as elevated levels of apoptosis markers and inflammation. In contrast, IR/LepA kidneys showed no signs of necrosis or inflammation with normal IL-6 and tall-like receptor 4 levels. LepA treatment led to upregulation in mRNA levels of leptin, leptin receptor, ERK1/2, STAT3, and transport molecule Na/H exchanger-3. Conclusions: Local, intrarenal postischemic LepA treatment at reperfusion prevented apoptosis and inflammation and was renoprotective. Selective intrarenal administration of LepA at reperfusion may provide a viable option for clinical implementation.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

Jonas¹,

Simon²,

Gilburd³

et al. 2023

Am J Nephrol

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“…leptin of 100 µg/kg b.w. (Ragy and RaMzy 2021) for three days. In the first two days, the doses were administrated before ischemia induction (Colak et al 2020).…”

Section: Methodsmentioning

confidence: 99%

“…A preliminary study was done to determine the effect of the vehicle, but there were insignificant differences between the non-treated OVIR group and the OVIR group treated with the vehicle. Both leptin doses (10 and 100 µg/kg) were selected based on the literature data (Erkasap et al 2004(Erkasap et al , 2017Sarsu et al 2015;Ragy and RaMzy 2021) indicating that these doses could improve oxidative stress, apoptosis, and inflammation associated with IR injuries. In addition, these doses are within the physiological range (Feng et al 2013;Pico et al 2021) because high leptin dose may suppress the ovarian functions (Shaikat et al 2021).…”

Section: Methodsmentioning

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).…”

mentioning

confidence: 99%

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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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Leptin and curcumin affect renal ischemia-reperfusion injury via modulation of P65 and Bax genes expression

Cited by 2 publications

References 46 publications

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

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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