Protective Effects of Traditional Polyherbs on Cisplatin-Induced Acute Kidney Injury Cell Model by Inhibiting Oxidative Stress and MAPK Signaling Pathway

Dachuri, VinayKumar; Song, Phil Hyun; Kim, Young Woo; Ku, Sae‐Kwang; Song, Chang‐Hyun

doi:10.3390/molecules25235641

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…When the confluence reached 80%, the cells were inoculated in a 6-well culture plate for cisplatin stimulation and exosome intervention experiments . Time selection: According to the actual situation of this study, the cells were first stimulated by different concentrations of cisplatin (10mM, 20mM) to detect the apoptosis of HK2 cells [22]. Then, 25ug exosomes were used to treat the cells to detect the effects of exosomes on the expression of apoptosis-related protein in HK2 cell.…”

Section: Cisplatin-induced Hk2 Cell Model Establishmentmentioning

confidence: 99%

The exosomes derived from urine of premature infants target MAPK8 via miR-30a-5p to protect cisplatin-induced acute kidney injury in mice

Luo

Fan

et al. 2021

Preprint

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Aim: Acute kidney injury (AKI), a global public health issue, not only causes millions of deaths every year, but is also a susceptible factor for chronic kidney disease (CKD). Nephrotoxic drugs are an important cause of AKI. There is still a lack of effective and satisfactory prevention method in clinical practice. This study investigated the protective effect of the exosomes derived from urine of premature infants on cisplatin-induced acute kidney injury. Methods: Isolation of exosomes from fresh urine of premature infants: The characteristics of exosomes were determined by flow cytometry, transmission electron microscopy and Western blotting. A C57BL/6 mice model of cisplatin-induced acute kidney injury was established. The mice in the experimental group were given 100ug exosomes dissolved in 200ul solution. The mice in the control group were given normal saline (200ul). These treatments were performed 24 hours after AKI was induced by intraperitoneal injection of cisplatin. To evaluate renal function, blood was drawn 24 hours after AKI model was established and serum creatinine (sCr) was measured. The mice were euthanized 72 hours after exosome treatment. The kidneys were collected for pathological examination, RNA and protein extraction, and the evaluation of renal tubular damage and apoptosis. In the in-vitro experiment, human renal cortex/proximal tubular cells (HK2) was induced by cisplatin to assess the protective ability of the exosomes derived from urine of premature infants. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blotting were used to evaluate the effect of exosomes treatment on the apoptosis of HK2 cells induced by cisplatin. Exosome microRNA sequencing technology and bioinformatics analysis method were applied to investigate the miRNAs enriched in exosomes and their target genes. The dual luciferase gene reporter system was used to detect the interaction of target genes. Results: Treatment of exosomes derived from urine of premature infants could decrease the level of serum creatinine and the apoptosis of renal tubular cell, inhibit the infiltration of inflammatory cell, protect mice from acute kidney injury induced by cisplatin and reduce mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes derived from urine of premature infants. It protected HK2 cells from cisplatin-induced apoptosis by targeting and down-regulating the 3'UTR of mitogen-activated protein kinases (MAPK8) mRNA. Conclusions: According to our results, the exosomes derived from urine of premature infants alleviated cisplatin-induced acute kidney injury in mice and inhibited the apoptosis of human proximal tubular cells (HK2) induced by cisplatin in vitro. MiR-30a-5p in exosomes inhibited cisplatin-induced MAPK activation, ameliorated apoptosis, and protected renal function. The exosomes derived from urine of premature infants provided a promising acellular therapy for AKI.

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Section: Cisplatin-induced Hk2 Cell Model Establishmentmentioning

confidence: 99%

The exosomes derived from urine of premature infants target MAPK8 via miR-30a-5p to protect cisplatin-induced acute kidney injury in mice

Luo

Fan

et al. 2021

Preprint

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“…DDP can reduce Nrf2 expression, increase the level of reduced coenzyme II (NADPH) oxidase 4 (NOX4) expression, and increase ROS levels, leading to mitochondrial dysfunction and damage to the body [ 28 ]. Many studies have shown that drugs with antioxidant and free radical scavenging activities, such as Scutellaria baicalensis and quercetin, can prevent and treat DDP-induced oxidative damage [ 13 , 29 , 30 ]. Altogether, these findings suggest that it is possible to treat cancer cachexia caused by DDP by improving oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Silibinin Alleviates Muscle Atrophy Caused by Oxidative Stress Induced by Cisplatin through ERK/FoxO and JNK/FoxO Pathways

Chi

Zhang

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cisplatin (DDP), a widely used chemotherapeutic drug in cancer treatment, causes oxidative stress, resulting in cancer cachexia and skeletal muscle atrophy. This study investigated the effects and activity of silibinin (SLI) in reducing DDP-induced oxidative stress and skeletal muscle atrophy in vivo and in vitro. SLI alleviated weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reduction induced by DDP and improved the reduction of grip force caused by DDP. SLI can attenuated the increase in reactive oxygen species (ROS) levels, the decrease in Nrf2 expression, the decrease in the fiber cross-sectional area, and changes in fiber type induced by DDP. SLI regulated the ERK/FoxO and JNK/FoxO pathways by downregulating the abnormal increase in ROS and Nrf2 expression in DDP-treated skeletal muscle and C2C12 myotube cells. Further, SLI inhibited the upregulation of MAFbx and Mstn, the downregulation of MyHC and MyoG, the increase in protein degradation, and the decrease of protein synthesis. The protective effects of SLI were reversed by cotreatment with JNK agonists and ERK inhibitors. These results suggest that SLI can reduce DDP-induced skeletal muscle atrophy by reducing oxidative stress and regulating ERK/FoxO and JNK/FoxO pathways.

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“…Regarding the nephrotoxicity unleashed by cisplatin, several mechanisms have been suggested, including oxidative stress, inflammation, mitochondrial dysfunction, DNA adducts and direct cytotoxicity to the renal tubules’ epithelial cells which will lead to acute kidney injury (AKI) [ 14 , 15 ]. About 20–30% of patients administered cisplatin-based treatment regimens end up suffering from acute kidney injury (AKI) [ 15 , 16 ]. Chronic or end-stage renal disease are fatal complications of AKI with socioeconomic impact.…”

Section: Introductionmentioning

confidence: 99%

“…Chronic or end-stage renal disease are fatal complications of AKI with socioeconomic impact. Dialysis and kidney replacement are the only treatments of end-stage renal disease [ 15 ]. Until now, there is no clinically curative or preventive drug for cisplatin-caused nephrotoxicity [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…Until now, there is no clinically curative or preventive drug for cisplatin-caused nephrotoxicity [ 16 ]. The symptomatic therapies of AKI embracing saline hydration, mannitol-based osmotic diuresis, and drug discontinuation [ 15 , 17 ]. However, forced diuresis by mannitol inflicts over-diuresis leading to dehydration in patients undergoing cisplatin chemotherapy [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

et al. 2021

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Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. Carrichtera annua extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato–nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on C. annua ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing 1H- and 13C-NMR spectral analyses. The isolated phytochemicals were trans-ferulic acid (1), kaempferol (2), p-coumaric acid (3), luteolin (4) and quercetin (5). Regarding our biological study, C. annua has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. C. annua has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin—C. annua extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of C. annua constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that C. annua is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals.

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Protective Effects of Traditional Polyherbs on Cisplatin-Induced Acute Kidney Injury Cell Model by Inhibiting Oxidative Stress and MAPK Signaling Pathway

Cited by 9 publications

References 44 publications

The exosomes derived from urine of premature infants target MAPK8 via miR-30a-5p to protect cisplatin-induced acute kidney injury in mice

The exosomes derived from urine of premature infants target MAPK8 via miR-30a-5p to protect cisplatin-induced acute kidney injury in mice

Silibinin Alleviates Muscle Atrophy Caused by Oxidative Stress Induced by Cisplatin through ERK/FoxO and JNK/FoxO Pathways

The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

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