Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury.

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miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A

Aging ◽

10.18632/aging.103160 ◽

2020 ◽

Vol 12 (11) ◽

pp. 10235-10245 ◽

Cited By ~ 1

Author(s):

Yong Xu ◽

Wei Jiang ◽

Lili Zhong ◽

Hailun Li ◽

Lin Bai ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Endothelial Growth Factor ◽

Acute Kidney Injury ◽

Growth Factor ◽

Kidney Injury ◽

Vascular Endothelial ◽

Endothelial Growth Factor ◽

And Oxidative Stress

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Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2853534 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 7

Author(s):

Hong-feng Zhang ◽

Jia-hong Wang ◽

Yan-li Wang ◽

Cheng Gao ◽

Yan-ting Gu ◽

...

Keyword(s):

Oxidative Stress ◽

Western Blot ◽

Signaling Pathway ◽

Kidney Injury ◽

Dependent Manner ◽

Salvianolic Acid ◽

Nrf2 Signaling Pathway ◽

Antioxidative Effects ◽

Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

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