Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation

Kang, Kyung Pyo; Kim, Duk Hoon; Jung, Yu Jin; Lee, Ae Sin; Lee, Sik; Lee, Sang Yong; Jang, Kyu Yun; Sung, Mi Jeong; Park, Sung Kwang; Kim, Won

doi:10.1093/ndt/gfp242

Cited by 129 publications

(96 citation statements)

References 36 publications

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“…15,20 Immunofluorescence stain analyses revealed that immunoreactive CXCL2 and CCL2 significantly increased in the tubules in renal cortex after treatment with LPS compared with control buffertreated Sirt2 +/+ mice. The CXCL2-and CCL2-immunoreactive cells were costained with Lectin.…”

Section: Sirt2 Is Expressed In the Normal Renal Proximal Tubular Epitmentioning

confidence: 99%

SIRT2 Regulates LPS-Induced Renal Tubular CXCL2 and CCL2 Expression

Jung¹,

Lee²,

Nguyễn-Thanh³

et al. 2015

Journal of the American Society of Nephrology

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Sirtuin 2 (SIRT2), a NAD + -dependent histone deacetylase, is involved in carcinogenesis and genomic instability and modulates proinflammatory immune responses. However, its role in renal inflammatory injury has not been demonstrated. In this study, we explored the expression patterns of CXCL2 and CCL2 in kidney tissue from Sirt2 2/2 and Sirt2 +/+ mice and in mouse proximal tubular epithelial (MPT) cells. CXCL2 and CCL2 were significantly downregulated at both the mRNA and the protein levels in kidneys of LPS-treated Sirt2 2/2 mice compared with those of LPS-treated Sirt2 +/+ mice. Furthermore, SIRT2 deficiency ameliorated LPS-induced infiltration of neutrophils and macrophages, acute tubular injury, and decrease of renal function. Supporting these observations, CXCL2 and CCL2 expression levels were lower in MPT cells treated with SIRT2-siRNA than in cells treated with control-siRNA, and adenovirus-mediated overexpression of SIRT2 in MPT cells significantly increased the LPS-induced expression of CXCL2 and CCL2 at the mRNA and protein levels. In addition, SIRT2 interacted with mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), and SIRT2-knockdown increased the acetylation of MKP-1 and suppressed the phosphorylation of p38 MAPK and c-Jun N-terminal kinase in LPS-treated MPT cells. SIRT2 also regulated p65 binding to the promoters of CXCL2 and CCL2. Taken together, these findings indicate that SIRT2 is associated with expression of renal CXCL2 and CCL2 and that regulation of SIRT2 might be an important therapeutic target for renal inflammatory injury.

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Section: Sirt2 Is Expressed In the Normal Renal Proximal Tubular Epitmentioning

confidence: 99%

SIRT2 Regulates LPS-Induced Renal Tubular CXCL2 and CCL2 Expression

Jung¹,

Lee²,

Nguyễn-Thanh³

et al. 2015

Journal of the American Society of Nephrology

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“…Nephrotoxicity, which is caused by the accumulation of cisplatin in the proximal tubule, has the potential to be a dose-limiting factor of this therapy. Previous studies reported that proximal tubular injury was caused due to increases in macrophage infiltration by cisplatin [3,4] and subsequent overproduction of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-α, in tubule cells [5][6][7]. Thus, inhibiting the production and secretion of TNF-α in macrophages may be advantageous in reducing cisplatin-induced renal injury.…”

Section: Introductionmentioning

confidence: 99%

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

Kim¹,

Yamamoto²,

Nakamura³

et al. 2013

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Cisplatin has been used for the treatment of various solid cancers or sarcomas; however, it can induce severe adverse effects. Among these adverse effects, nephrotoxicity, which has the potential to be a dose-limiting factor of this agent, develops due to the secretion of tumor necrosis factor-α (TNF-α) from macrophages; however, the precise mechanisms are still unclear. To elucidate possible mechanisms, we investigated the involvement of mitogen-activated protein kinases (MAPK) and reactive oxygen species (ROS) in cisplatin-induced TNF-α mRNA expression and protein production in the mouse macrophage-like cell line, RAW 264. Cisplatin (1 μM) significantly increased TNF-α mRNA expression and protein production. Extracellular-regulated kinase (ERK) and p38 MAPK, but not c-Jun N-terminal kinase (JNK), phosphorylation increased in response to cisplatin. Although an ERK inhibitor (PD98059) suppressed both cisplatin-induced TNF-α mRNA expression and its protein production, a p38 MAPK inhibitor (SB203580) decreased TNF-α protein production only. A JNK inhibitor (SP600125) had no effect on cisplatin-induced TNF-α mRNA expression. Furthermore, a scavenger of ROS, N,N'-dimethylthiourea, suppressed both ERK activation and TNF-α mRNA expression. These results suggest that the phosphorylation of ERK by ROS is involved in cisplatin-induced TNF-α mRNA expression and that the signaling pathway of p38 MAPK is related to TNF-α protein production.

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“…The cytotoxic effect of CIS is believed to result mainly from its interaction with DNA via the formation of covalent adducts between certain DNA bases and platinum compounds [39]. CIS-induced nephrotoxicity can result in severe renal tubular injury leading to acute renal failure [40].…”

Section: Discussionmentioning

confidence: 99%

Chemoprotective Effect of Noni (Morinda Citrifolia L.) Fruit Juice Against Cisplatin-Induced Nephrotoxicity

Ali

Mruthunjaya

Nandini

et al. 2016

Int J Pharm Pharm Sci

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Objective: Cisplatin (CIS) consumption has become a common problem that affects the health of patients around the globe. Kidney has been suspected to be particularly susceptible to the destructive effects of CIS and nephrotoxic effects are still contentious which in turn affects the Quality of Life (QoL) of patients and increase the mortality rate. This study was conducted to investigate the nephroprotective effect of Noni Juice (NJ) and Divine Noni Gold (DNG) as herbal medicine with established antioxidant properties against the controversial nephrotoxic effect of CIS in mice. Methods:Mice were divided into four groups, each group contained six mice. Group I was kept as normal, Group II received CIS (5.0 mg/kg b. wt. i. p.) on day one for 14 d. Group III and IV received NJ (0.35 ml/mouse p. o.) and DNG (0.35 ml/mouse p. o.) respectively once daily for 14 d, Group V received CIS (5.0 mg/kg b. wt. i. p.) on day one and NJ (0.35 ml/mouse p. o.) once daily for 14 d. Similarly, Group VI received CIS (5.0 mg/kg b. wt. i. p.) on day one and DNG (0.35 ml/mouse p. o.) once daily for 14 d. On day 15 blood from all the mice was collected from the carotid vein and cardiac puncture routes, and the biochemical markers viz. lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and urea were assessed. Kidney from all the animals was isolated, and catalase (CAT), glutathione (GSH), superoxide dismutase (SOD), thiols and lipid peroxidase (LPO) were estimated.Results: CIS-induced marked kidney injury; congestion of tubules, glomerular distortion foci, thickened and blocked blood vessels. Also showed significant elevation of LDH, CPK, and urea with significant inhibition of CAT, GSH, SOD, thiols activities and simultaneously elevation of LPO level. Co-administration of NJ and DNG respectively with CIS protected kidney tissues via oxidative stress inhibition.Conclusion: NJ and DNG possess protective effect against CIS-induced cellular damage in the kidney by decreasing the level of serum biochemical markers, enhancing the level of enzymatic and non-enzymatic antioxidants and maintaining the LPO level. Results suggest that NJ and DNG have strong nephroprotective effect against CIS-induced nephrotoxicity.

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Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation

Abstract: These results suggest that alpha-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-kappaB activity.

Cited by 129 publications

References 36 publications

SIRT2 Regulates LPS-Induced Renal Tubular CXCL2 and CCL2 Expression

SIRT2 Regulates LPS-Induced Renal Tubular CXCL2 and CCL2 Expression

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

Chemoprotective Effect of Noni (Morinda Citrifolia L.) Fruit Juice Against Cisplatin-Induced Nephrotoxicity

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