Dexmedetomidine Ameliorates Acute Stress‐Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

Chen, Yongping; Feng, Xiujing; Hu, Xueyuan; Sha, Jichen; Li, Bei; Zhang, Huayun; Fan, Honggang

doi:10.1155/2018/4035310

Cited by 92 publications

(94 citation statements)

References 67 publications

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“…using Pi3K-knockout mice, it was previously revealed that a conventional dose of cP was more lethal in these knockout mice, indicating the importance of the Pi3K/aKT pathway in protecting the kidneys (21). dexmedetomidine (dex), a highly selective α 2 adrenoreceptor (α 2 AR) agonist, has been reported to be beneficial for the prevention of numerous types of kidney diseases, including acute stress-induced kidney injury (22), ischemia-reperfusion and sepsis-induced kidney injuries (23)(24)(25). it has also been demonstrated that dex protects the kidney against cP-induced AKI by regulating apoptosis and the inflammatory response (26).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

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cisplatin (cP) is an effective antineoplastic agent; however, cP-induced acute kidney injury (aKi) seriously affects the prognosis of patients with cancer. endoplasmic reticulum (er) stress (erS)-induced apoptosis serves a pivotal role in the pathogenesis of cP-induced aKi. dexmedetomidine (dex), a potent α 2 adrenergic agonist, has been reported to exert protective effects against aKi. However, the protective effects of dex against cP-induced aKi and the potential molecular mechanisms remain unknown. in the present study, male Sprague-dawley rats were divided into four groups (n=10/group), as follows: control group; cP group, rats received an intraperitoneal (i.p.) injection of 5 mg/kg cP; dex + cP group, rats received an i.p. injection of 25 µg/kg dex immediately after cP treatment; and dex + cP + atipamezole (atip) group, rats received an i.p. injection of 250 µg/kg atip, an α 2 adrenoreceptor (α 2 ar) antagonist, and then received the same treatment as the dex + cP group. rats were anesthetized and sacrificed 96 h after CP injection. Subsequently, serum blood urea nitrogen (Bun) and serum creatinine (Scr) were analyzed, and kidney samples were collected for analyses. Pathological changes were examined using hematoxylin and eosin staining, and protein expression levels were assessed using western blotting and immunohistochemical staining. in addition, apoptosis was examined using a terminal deoxynucleotidyl transferase duTP nick-end labeling assay. The present results suggested that dex protected against cP-induced aKi by attenuating histological changes in the kidney, serum Bun and Scr production. Furthermore, the expression levels of 78-kda glucose-regulated protein, c/eBP homologous protein and caspase-12, and the apoptotic rate in the kidney were decreased following dex treatment. in addition, the expression levels of phosphorylated (p)-Pi3K and p-aKT in the dex + cP group were significantly increased. Conversely, the renoprotective effects of dex were attenuated following the addition of atip. in conclusion, dex may alleviate cP-induced aKi by attenuating erS-induced apoptosis, at least in part, via the α 2 ar/Pi3K/aKT signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

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“…ROS can lead to DNA fragmentation and cell apoptosis [15]. Chen et al demonstrated that inhibiting ROS can attenuate apoptosis in kidney injury [23]. In our study, we did not assess the effect of CRSAS in oxidative stress.…”

Section: Cg 4hmentioning

confidence: 74%

The Mechanisms of the Herbal Components of CRSAS on HK‐2 Cells in a Hypoxia/Reoxygenation Model Based on Network Pharmacology

Xie

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Acute kidney injury is a global problem, which brings a great burden to the society and family. The component of rhubarb, Salvia miltiorrhiza, Astragalus membranaceus, and safflower (CRSAS) has been proved as an useful agent to treat acute kidney injury (AKI) patients in China. Objective. To assess the effect of CRSAS on human renal tubular epithelial cells (HK-2) after the hypoxia/reoxygenation (H/R) and investigate the potential mechanisms. Methods. Network pharmacology was used to predict the potential pathways shared by CRSAS and AKI. Cell counting kit-8 (CCK-8) was used to assess the HK-2 vitality. Apoptosis of HK-2 cells was detected by carboxyfluorescein succinimidyl ester/propidium iodide (CFSF/PI) staining. Expression of GRP78, CHOP, caspase-3, and Bax was detected by western blot and quantitative real-time RT-PCR. Result. CRSAS and AKI shared the endoplasmic reticulum stress (ERS) pathway based on network pharmacology analysis. CRSAS increases the vitality of HK-2 cells and reduces the apoptosis of HK-2 cells induced by H/R injury. The expression of GRP78 and CHOP in CRSAS groups was lower than that of control groups. Conclusions. H/R can induce HK-2 cell apoptosis and ERS. CRSAS can reduce HK-2 cell apoptosis by inhibiting the ERS. Therefore, CRSAS might be able to treat kidney disease due to I/R injury. Animal experiment should be done to further prove our finding.

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“…Tu et al [30] reported that ApoE-derived peptide reduces oxidative stress and improves outcome in an ischemic stroke mouse model, indicating that APOE may also regulate oxidative stress in the acute brain pathological process. Chen et al [31] reported that oxidative stress is related to ROS/JNK signaling pathway acute stress-induced kidney injury. Our study revealed a regulation of the JNK pathway by APOE, which indicates that APOE may modulate oxidative stress via the JNK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Deficiency Aggravates Neuronal Injury by Enhancing Neuroinflammation via the JNK/c-Jun Pathway in the Early Phase of Experimental Subarachnoid Hemorrhage in Mice

Pang

Peng

et al. 2019

Oxidative Medicine and Cellular Longevity

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Neuronal injury is the primary cause of poor outcome after subarachnoid hemorrhage (SAH). The apolipoprotein E (APOE) gene has been suggested to be involved in the prognosis of SAH patients. However, the role of APOE in neuronal injury after SAH has not been well studied. In this study, SAH was induced in APOE-knockout (APOE-/-) and wild-type (WT) mice to investigate the impact of APOE deficiency on neuronal injury in the early phase of SAH. The experiments of this study were performed in murine SAH models in vivo and primary cultured microglia and neurons in vitro. The SAH model was induced by endovascular perforation in APOE-/- and APOE WT mice. The mortality rate, weight loss, and neurological deficits were recorded within 72 h after SAH. The neuronal injury was assessed by detecting the neuronal apoptosis and axonal injury. The activation of microglia was assessed by immunofluorescent staining of Iba-1, and clodronate liposomes were used for inhibiting microglial activation. The expression of JNK/c-Jun was evaluated by immunofluorescent staining or western blotting. The expression of TNF-α, IL-1β, and IL-6 was evaluated by ELISA. Primary cultured microglia were treated with hemoglobin (Hb) in vitro for simulating the pathological process of SAH. SP600125, a JNK inhibitor, was used for evaluating the role of JNK in neuroinflammation. Nitrite production was detected for microglial activation, and flow cytometry was performed to detect apoptosis in vitro. The results suggested that SAH induced early neuronal injury and neurological deficits in mice. APOE deficiency resulted in more severe neurological deficits after SAH in mice. The neurological deficits were associated with exacerbation of neuronal injury, including neuronal apoptosis and axonal injury. Moreover, APOE deficiency enhanced microglial activation and related inflammatory injury on neurons. Inhibition of microglia attenuated neuronal injury in mice, whereas inhibition of JNK inhibited microglia-mediated inflammatory response in vitro. Taken together, JNK/c-Jun was involved in the enhancement of microglia-mediated inflammatory injury in APOE-/- mice. APOE deficiency aggravates neuronal injury which may account for the poor neurological outcomes of APOE-/- mice. The possible protective role of APOE against EBI via the modulation of inflammatory response indicates its potential treatment for SAH.

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Dexmedetomidine Ameliorates Acute Stress‐Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

Cited by 92 publications

References 67 publications

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

The Mechanisms of the Herbal Components of CRSAS on HK‐2 Cells in a Hypoxia/Reoxygenation Model Based on Network Pharmacology

Apolipoprotein E Deficiency Aggravates Neuronal Injury by Enhancing Neuroinflammation via the JNK/c-Jun Pathway in the Early Phase of Experimental Subarachnoid Hemorrhage in Mice

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