Protective Effects of DHA-PC against Vancomycin-Induced Nephrotoxicity through the Inhibition of Oxidative Stress and Apoptosis in BALB/c Mice

Shi, Hao‐Hao; Zou, Jun; Zhang, Tiantian; Che, Hongxia; Gao, Xiang; Wang, Cheng cheng; Wang, Yuming; Xue, Changhu

doi:10.1021/acs.jafc.7b04565

Cited by 34 publications

(37 citation statements)

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“…These studies have been reviewed in detail 111 . Since then, spirulina and pycnogenol , 112 mitoTEMPO, naringenin, 113 a free radical scavenger zingerone, 114, 115 DHA‐enriched phosphatidylcholine (DHA‐PC), 116 rutin, 117 and silymarin 118 have been evaluated in animal studies. In our opinion, the antioxidants that are most ready for clinical trials include preparations that are already clinically available, such as atorvastatin, vitamin C, vitamin E, N‐acetylcysteine, erythropoietin, and erdosteine.…”

Section: Potential Strategies For Preventionmentioning

confidence: 99%

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

et al. 2020

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Vancomycin is a recommended therapy in multiple national guidelines. Despite the common use, there is a poor understanding of the mechanistic drivers and potential modifiers of vancomycin-mediated kidney injury. In this review, historic and contemporary rates of vancomycin-induced kidney injury (VIKI) are described, and toxicodynamic models and mechanisms of toxicity from preclinical studies are reviewed. Aside from known clinical covariates that worsen VIKI, preclinical models have demonstrated that various factors impact VIKI, including dose, route of administration, and thresholds for pharmacokinetic parameters. The degree of acute kidney injury (AKI) is greatest with the intravenous route and higher doses that produce larger maximal concentrations and areas under the concentration curve. Troughs (i.e., minimum concentrations) have less of an impact. Mechanistically, preclinical studies have identified that VIKI is a result of drug accumulation in proximal tubule cells, which triggers cellular oxidative stress and apoptosis. Yet, there are several gaps in the knowledge that may represent viable targets to make vancomycin therapy less toxic. Potential strategies include prolonging infusions and lowering maximal concentrations, administration of antioxidants, administering agents that decrease cellular accumulation, and reformulating vancomycin to alter the renal clearance mechanism. Based on preclinical models and mechanisms of toxicity, we propose potential strategies to lessen VIKI.

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Section: Potential Strategies For Preventionmentioning

confidence: 99%

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

et al. 2020

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“…The mitochondrial apoptosis pathway played an increasingly great role in drug-induced nephrotoxicity [ 22 ]. An large number of studies have shown that vancomycin treatment could increase the expression of pro-apoptotic proteins (Bax, Cyt-C, Caspase 3, and Caspase 9) and decrease the expression of the Bcl-2 protein [ 12 ]. Our results suggested that the administration of DHA-acylated AST diesters was more effective than the recombination of unesterified AST and DHA in increasing the expression of Bcl-2 protein and inhibiting the expression of several apoptotic proteins, especially the changes of Bax and cleaved-Caspase 3.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies showed that AST esters had better biological activities, including anti-cancer activity, liver protection, and antioxidant function compared with unesterified AST [ 10 ]. A great number of animal and clinical data have shown that DHA possessed a significant alleviation on kidney disease [ 11 , 12 ]. Our previous research showed that dietary supplementation with DHA-acylated AST diester could alleviate the behavioral deficits in the mice with Parkinson’s disease and cognitive disorders in model mice of Alzheimer’s disease, which was better than that of unesterified AST [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic Acid-Acylated Astaxanthin Esters Exhibit Superior Renal Protective Effect to Recombination of Astaxanthin with DHA via Alleviating Oxidative Stress Coupled with Apoptosis in Vancomycin-Treated Mice with Nephrotoxicity

et al. 2021

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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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“…Hepatic injury was evaluated using the following parameters: bile-duct proliferation, nuclear condensation, hepatocyte necrosis, fatty degeneration, and inflammatory cell infiltration ( Kraieski et al., 2017 ; Ma et al., 2012 ). The pathological changes in kidneys were assessed by renal tubular dilatation and atrophy, hyaline vacuolar degeneration, and tubular epithelial cell swelling or necrosis ( Ma et al., 2018 ; Shi et al., 2018 ). Intestinal morphology analyses were carried out on 2 cross-sections per sample, 15 well-oriented villus per section (30 intact well-oriented villus per sample) were measured ( Poloni et al., 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Tolerance and safety evaluation of sodium sulfate: A subchronic study in laying hens

et al. 2021

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Sodium sulfate (Na 2 SO 4 ) is a readily available chlorine-free source of sodium, which could be used to reduce sodium chloride to maintain the ratio between chlorine and sodium in poultry diets. Dietary supplementation with excessive levels of Na 2 SO 4 might be detrimental to bird's health and performance. A subchronic study was carried out to investigate the potential adverse effects of an accidental oversupply of Na 2 SO 4 in the diets of laying hens. Four hundred and fifty 21-week-old Hy-Line White layers were randomly assigned to 5 treatments with 6 replicates. The birds were fed diets supplemented with 0 (control), 0.3%, 0.6%, 1.5%, and 3.0% Na 2 SO 4 for 8 weeks. Laying performance, egg quality parameters, clinical blood parameters, histopathology, intestinal barrier functions, and intestinal microflora composition were measured. No clinical signs of intoxication or mortality were observed during the experimental period. The results of this study showed that the optimal levels of Na 2 SO 4 (0.3% to 0.6%) significantly improved the laying rates, average daily egg mass, and eggshell quality of hens compared to the control ( P < 0.05). However, 3.0% Na 2 SO 4 produced negative effects on laying performance, eggshell quality, blood biochemistry, and particularly on liver and kidney pathology, and intestinal morphology and barrier functions compared with the controls. Although minor changes were observed in clinical blood parameters of hens receiving 1.5% Na 2 SO 4 , these were not considered to be of toxicological significance due to the absence of any organ pathological changes in hens. In conclusion, our results indicated that a Na 2 SO 4 concentration of 1.5% was non-deleterious to laying hens after a daily administration for 56 d, namely that dietary supplementation of up to 5 times the maximum recommended dose is safely tolerated by laying hens.

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Protective Effects of DHA-PC against Vancomycin-Induced Nephrotoxicity through the Inhibition of Oxidative Stress and Apoptosis in BALB/c Mice

Cited by 34 publications

References 50 publications

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

Docosahexaenoic Acid-Acylated Astaxanthin Esters Exhibit Superior Renal Protective Effect to Recombination of Astaxanthin with DHA via Alleviating Oxidative Stress Coupled with Apoptosis in Vancomycin-Treated Mice with Nephrotoxicity

Tolerance and safety evaluation of sodium sulfate: A subchronic study in laying hens

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