A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats

Youssef, Mahmoud I.; Mahmoud, A. A.; Abdel-Ghany, Rasha

doi:10.1016/j.bcp.2015.04.010

Cited by 34 publications

(35 citation statements)

References 81 publications

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“…It was found in our study that the activity of SOD and GSH level were decreased while the MDA level was increased in the renal tissue in diabetic RI/RI, demonstrating an oxidative injury. During the process of I/R injury, inflammatory reactions are activated, resulting in the formation of inflammatory cytokines, such as IL-6 and IL-10 [9, 27, 43, 44]. We also found that the expressions of IL-10 and IL-6 in the renal tissue were elevated in this diabetic RI/RI model.…”

Section: Discussionsupporting

confidence: 52%

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Hu¹,

Tong²,

Xu³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS), and nitroso-redox imbalance. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM). Methods: The bilateral renal arteries and veins of streptozotocin (STZ)-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR) and NPS-2143 (antagonist of CaSR) at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM), and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM), commercial kits, enzyme-linked immunosorbent assay (ELISA), and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

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Section: Discussionsupporting

confidence: 52%

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Hu¹,

Tong²,

Xu³

et al. 2018

Kidney Blood Press Res

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“…A similar increase in SBP with IR and glycerol‐induced rhabdomyolysis‐ARI was reported previously . IR injury and glycerol‐induced rhabdomyolysis‐ARI were reported to increase kidney oxidative stress and NADPH oxidase which are considered as important sources of ROS production . We observed higher ROS production in our two models (MDA and NADPH oxidase) with elevated kidney NO content compared to control rats.…”

Section: Discussionsupporting

confidence: 90%

Doxazosin down‐regulates sodium‐glucose cotransporter‐2 and exerts a renoprotective effect in rat models of acute renal injury

Rezq

Nasr

Shaheen

et al. 2019

Basic Clin Pharma Tox

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Sodium-glucose cotransporter-2 (SGLT2) is known to be involved in the progression of acute renal injury (ARI) and is regulated by different mediators in the kidneys including extracellular signal-regulated kinase (ERK), hypoxia-inducible factor 1 alpha (HIF1α) and prostaglandin E2 (PGE2). In the present study, we investigated the possible protective effect of doxazosin on renal ischaemia/reperfusion (IR) and glycerol-induced ARI by determining its effect on SGLT2 via modifying ERK-HIF1α pathway and/or PGE2. Rats were divided into control, sham or IR where the rats received the vehicle, doxazosin (8 mg/kg) or the SGLT2 inhibitor, dapagliflozin (10 mg/kg) for 3 days followed by 45 minutes bilateral renal ischaemia then 24 hours reperfusion. Another group of rats received the vehicle, doxazosin or dapagliflozin for three days followed by injection of 50% glycerol (8 mL/kg, IM) or saline. Kidney function tests, systolic blood pressure (SBP), oxidative stress markers (malondialdehyde [MDA] and NADPH oxidase), nitric oxide (NO), inducible nitric oxide synthase (iNOS), HIF1α, ERK phosphorylation and PGE2 levels were determined.Additionally, renal sections were used for immunological expression of SGLT2. ARI rats showed significantly increased SBP; worsened kidney function tests; increased oxidative stress, iNOS, NO, HIF1α levels; and decreased PGE2 and ERK phosphorylation along with up-regulated SGLT2. Doxazosin treatment protected against the kidney damage and attenuated the associated biochemical changes. Doxazosin has a direct renoprotective effect possibly by down-regulating SGLT2. K E Y W O R D Sacute renal injury, extracellular signal-regulated kinase, hypoxia-inducible factor 1, prostaglandin E2, sodium-glucose cotransporter 2 414 | REZQ Et al.

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“…[3,[12][13][14] In a study, Tai et al [12] created an experimental model with bilateral kidney I/R injury and examined cardiac function. They found that kidney I/R injury was associated with cardiac dysfunction and niacin reduced myocardial oxidative stress using indicators such as serum troponin, urea, creatinine, and malondialdehyde.…”

Section: Discussionmentioning

confidence: 99%

“…In another study, the effects of sitagliptin and furosemide were examined on renal I/R-induced myocardial injury, and they found protective effects using biochemical and immunohistochemical indicators. [3] In our experimental model, we designed bilateral kidney I/R model and we explored for the first time the protective effects of cilostazol and rosuvastatin on kidney I/R injury and remote cardiac reperfusion injury using biochemical and immunohistochemical indicators.…”

Section: Discussionmentioning

confidence: 99%

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Investigation the effects of cilostazol and rosuvastatin on kidney and heart: An experimental acute kidney and heart injury model

İşcan¹

2017

Turk Gogus Kalp Dama

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ÖZAmaç: Bu çalışmada, deneysel bir modelde ameliyat öncesi silostazol ve rosuvastatin tedavisinin böbrek iskemi/reperfüzyon hasarına olan etkisi ve uzak kalp reperfüzyon hasarı üzerine olan etkisi araştırıldı.Ça lış mapla nı:Toplam 35 adet dişi Sprague-Dawley sıçan rastgele beş gruba ayrıldı (n=7). Median laparotomi yapılarak, her iki böbreğe 45 dakika süren iskemi uygulandı. Cerrahi girişimin üç gün öncesinden başlayarak oral tedavi uygulandı (20 mg/kg silostazol, 10 mg/kg rosuvastatin ve 20 mg/kg cilostazol + 10 mg/kg rosuvastatin). Cerrahi girişimden bir gün sonra ise kan örnekleri ve böbrek ve kalp doku örnekleri alındı. Bul gu lar:Böbrek dokularının immünhistokimyasal değerlendirmesinde tümör nekroz faktör-alfa ve hipoksi ile indüklenebilir faktör-1 alfa immünreaktivitesinin silostazol, rosuvastatin ve silostazol + rosuvastatin grubunda, iskemi/ reperfüzyon hasarı grubuna kıyasla anlamlı düzeyde daha düşük olduğu tespit edildi (p<0.05). Kalp dokularının immünhistokimyasal değerlendirmesinde tümör nekroz faktör-alfa immünreaktivitesi, iskemi/reperfüzyon hasarı grubuna kıyasla silostazol grubunda anlamlı düzeyde daha düşüktü. Hipoksi ile indüklenebilir faktör-1 alfa immünreaktivitesi, silostazol, rosuvastatin ve silostazol + rosuvastatin grubunda, iskemi/reperfüzyon hasarı grubuna kıyasla, anlamlı düzeyde daha düşüktü (p<0.05). İskemi/reperfüzyon hasarı grubuna kıyasla, silostazol, rosuvastatin ve silostazol + rosuvastatin grubunda, serum üre, kreatinin, kreatin kinaz-kas ve beyin ve troponin düzeyleri anlamlı düzeyde daha düşüktü (p<0.05).So nuç: Silostazol ve rosuvastatinin böbrek iskemi/reperfüzyon ve uzak kardiyak reperfüzyon hasarı üzerinde koruyucu etkileri olmakla birlikte, bu etki kombine tedaviye kıyasla silostazol tedavisi ile artabilir.Anah tarsöz cük ler: Kalp; iskemi/reperfüzyon hasarı, böbrek. ABSTRACTBackground: In this study, we aimed to assess the effects of preoperative cilostazol and rosuvastatin therapy on kidney ischemia/ reperfusion injury and remote cardiac reperfusion injury in an experimental model.

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A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats

Cited by 34 publications

References 81 publications

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Doxazosin down‐regulates sodium‐glucose cotransporter‐2 and exerts a renoprotective effect in rat models of acute renal injury

Investigation the effects of cilostazol and rosuvastatin on kidney and heart: An experimental acute kidney and heart injury model

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