β-Lapachone enhances Mre11-Rad50-Nbs1 complex expression in cisplatin-induced nephrotoxicity

Kim, Tae Won; Kim, Young Jung; Kim, Hyun Tae; Park, Se Ra; Jung, Ju Young

doi:10.1016/j.pharep.2015.06.007

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…An estimated human clinical equivalent dose (or range of doses) of lansoprazole (12.5 mg/kg) and a higher dose (25 mg/kg) were tested in this experiment. Based on the doses used in previous experiments, 18 a single dose of 18 mg/kg cisplatin was chosen to induce AKI in C57BL/6 mice. The experimental design is illustrated in Figure 1A.…”

Section: Resultsmentioning

confidence: 99%

Lansoprazole promotes cisplatin‐induced acute kidney injury via enhancing tubular necroptosis

Pang

Huang

et al. 2021

J Cellular Molecular Medi

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Acute kidney injury (AKI) is the main obstacle that limits the use of cisplatin in cancer treatment. Proton pump inhibitors (PPIs), the most commonly used class of medications for gastrointestinal complications in cancer patients, have been reported to cause adverse renal events. However, the effect of PPIs on cisplatin‐induced AKI remains unclear. Herein, the effect and mechanism of lansoprazole (LPZ), one of the most frequently prescribed PPIs, on cisplatin‐induced AKI were investigated in vivo and in vitro. C57BL/6 mice received a single intraperitoneal (i.p.) injection of cisplatin (18 mg/kg) to induce AKI, and LPZ (12.5 or 25 mg/kg) was administered 2 hours prior to cisplatin administration and then once daily for another 2 days via i.p. injection. The results showed that LPZ significantly aggravated the tubular damage and further increased the elevated levels of serum creatinine and blood urea nitrogen induced by cisplatin. However, LPZ did not enhance cisplatin‐induced tubular apoptosis, as evidenced by a lack of significant change in mRNA and protein expression of Bax/Bcl‐2 ratio and TUNEL staining. Notably, LPZ increased the number of necrotic renal tubular cells compared to that by cisplatin treatment alone, which was further confirmed by the elevated necroptosis‐associated protein expression of RIPK1, p‐RIPK3 and p‐MLKL. Furthermore, LPZ deteriorated cisplatin‐induced inflammation, as revealed by the increased mRNA expression of pro‐inflammatory factors including, NLRP3, IL‐1β, TNF‐α and caspase 1, as well as neutrophil infiltration. Consistently, in in vitro study, LPZ increased HK‐2 cell death and enhanced inflammation, compared with cisplatin treatment alone. Collectively, our results demonstrate that LPZ aggravates cisplatin‐induced AKI, and necroptosis may be involved in the exacerbation of kidney damage.

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Section: Resultsmentioning

confidence: 99%

Lansoprazole promotes cisplatin‐induced acute kidney injury via enhancing tubular necroptosis

Pang

Huang

et al. 2021

J Cellular Molecular Medi

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“…Under cellular stresses or stimuli, such as cisplatin administration, mitochondria significantly increase their production of ROS. Further, cisplatin increases intracellular accumulation of ROS by decreasing expression of endogenous antioxidant enzymes such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) [49,64,65,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89]. Oxidative stress occurs when the cell is unable to respond to, or neutralize, the amount of ROS being generated.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury

Holditch

Brown

Lombardi

et al. 2019

IJMS

274

232

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Cisplatin is a widely used chemotherapeutic agent used to treat solid tumours, such as ovarian, head and neck, and testicular germ cell. A known complication of cisplatin administration is acute kidney injury (AKI). The development of effective tumour interventions with reduced nephrotoxicity relies heavily on understanding the molecular pathophysiology of cisplatin-induced AKI. Rodent models have provided mechanistic insight into the pathophysiology of cisplatin-induced AKI. In the subsequent review, we provide a detailed discussion of recent advances in the cisplatin-induced AKI phenotype, principal mechanistic findings of injury and therapy, and pre-clinical use of AKI rodent models. Cisplatin-induced AKI murine models faithfully develop gross manifestations of clinical AKI such as decreased kidney function, increased expression of tubular injury biomarkers, and tubular injury evident by histology. Pathways involved in AKI include apoptosis, necrosis, inflammation, and increased oxidative stress, ultimately providing a translational platform for testing the therapeutic efficacy of potential interventions. This review provides a discussion of the foundation laid by cisplatin-induced AKI rodent models for our current understanding of AKI molecular pathophysiology.

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“…Cisplatin-induced DNA damage is recognized by special cellular machinery, which includes MRE11-RAD50-NBS1 (MRN) complex [17,18], hMSH2 of the mismatch repair (MMR) complex, the nonhistone chromosomal high-mobility groups 1 and 2 proteins (HMG1 and HMG 2) and the transcriptional factor "TATA-binding protein" (TBP) [19]. The last is a key component of the transcription factor IID, required for the initiation of transcription of all three eukaryotic RNA polymerases [20].…”

Section: Mechanisms Of Apoptotic Cell Death Induced By Platinum-conta...mentioning

confidence: 99%

Platinum drugs and taxanes: can we overcome resistance?

et al. 2021

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Cancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms “cell death” and “apoptosis” interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.

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β-Lapachone enhances Mre11-Rad50-Nbs1 complex expression in cisplatin-induced nephrotoxicity

Abstract: Although, it remains unclear how β-lapachone induces MRN complex expression, our findings suggest that β-lapachone might affect MRN complex expression and participate in DNA damage recovery in cisplatin-induced nephrotoxicity.

Cited by 3 publications

References 21 publications

Lansoprazole promotes cisplatin‐induced acute kidney injury via enhancing tubular necroptosis

Lansoprazole promotes cisplatin‐induced acute kidney injury via enhancing tubular necroptosis

Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury

Platinum drugs and taxanes: can we overcome resistance?

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