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BMC Complementary Medicine and Therapies

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Open Access 01-12-2024 | Acute Kidney Injury | Research

JianPiYiShen formula prevents cisplatin-induced acute kidney injury in mice by improving necroptosis through MAPK pathway

Authors: Zhongtang Li, Riming He, Jiahui Liu, Xiaoming Jin, Beibei Jiang, Yunlan Lao, Shudong Yang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2024

Abstract

Background

Acute kidney injury (AKI), characterized by necroptosis and activation of MAPK pathway, causes sudden declines in renal function. To date, efficacious treatments are lacking. JianPiYiShen Formula (JPYSF) has a protective effect on the kidneys. The aim of this study is to explore the mechanism of JPYSF in cisplatin-induced AKI.

Methods

Male C57/BL6J mice were divided into control group, cisplatin group and cisplatin + JPYSF group. Before establishing the model, the cisplatin + JPYSF group was administered JPYSF (18.35 g/kg/day) by gavage for 5 consecutive days. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to establish AKI model. Measurement of renal function and H&E staining were performed to assess renal damage. WB, PCR, TUNEL staining and immunohistochemistry were used to detect related indicators of mitochondrial function, oxidative stress, necroptosis, inflammation and MAPK pathway. And one-way analysis of variance was used to compare group differences.

Results

Compared with the cisplatin group, JPYSF can attenuate AKI, reflected by the decrease in Scr and BUN levels, the improvement of renal tubular injury, and the downregulation of NGAL and KIM1. Cisplatin can induce mitochondrial dysfunction and oxidative stress, triggering necroptosis. In this study, JPYSF improved mitochondrial dysfunction to enhance oxidative stress, as manifested by upregulation of OPA1, PGC-1α, SOD and CAT, and downregulation of DRP1 and MFF. Then JPYSF showed a significant protective effect in necroptosis, as embodied by reduced number of TUNEL-positive cells, decreased the gene expression of RIPK3 and MLKL, as well as downregulation the proteins expression of P-RIPK1, P-RIPK3, and P-MLKL. Moreover, necroptosis can aggravate inflammation. JPYSF ameliorated inflammation by improving inflammatory and anti-inflammatory indexes, including downregulation of TNF-α, IL-6, MCP-1 and LY6G, and upregulation of IL-10. In addition, JPYSF also inhibited MAPK pathway to improve necroptosis by decreasing the expression of P-JNK and P-ERK.

Conclusion

Our data showed that JPYSF prevents cisplatin-induced AKI by improving necroptosis through MAPK pathway, which is related to the improvement of mitochondrial dysfunction, oxidative stress, and inflammation.

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Bellomo R, Kellum JA, Ronco C. Acute kidney injury. The Lancet [Internet]. 2012;380(9843):756–66. https://doi.org/10.1016/S0140-6736(11)61454-2.

Fang Cyan, Lou D, yong, Zhou L, qin, Wang Jcheng, Yang B, He Q. Natural products: potential treatments for cisplatin-induced nephrotoxicity. Acta Pharmacol Sin. 2021;42(12):1951–69.CrossRefPubMedPubMedCentral

Mcsweeney KR, Gadanec LK, Zulli A. Mechanisms of Cisplatin-Induced Acute kidney Injury. Cancers (Basel). 2021;13(1572):1–42.

Liu X, Li L, Ding X, Ren Y, Zhang L, Shao Z. The role of necroptosis in disease and treatment. 2021;(November):730–55.

Xu Y, Ma H, Shao J, Wu J, Zhou L, Zhang Z, et al. A role for tubular necroptosis in cisplatin-induced AKI. J Am Soc Nephrol. 2015;26(11):2647–58.CrossRefPubMedPubMedCentral

Basile DP, Anderson MD, Sutton TA. Pathophysiology of Cisplatin-Induced Acute Kidney Injury. Compr Physiol [Internet]. 2011;2(2):1303–53. Available from: http://www.pubmedcentral.nih.gov/articlerenderfcgi?artid=3919808&tool=pmcentrez&rendertype=abstract.

Anders HJ. Necroptosis in Acute kidney Injury. Nephron. 2018;139(4):342–8.MathSciNetCrossRefPubMed

Mulay SR, Linkermann A, Anders HJ. Necroinflammation in kidney disease. J Am Soc Nephrol. 2016;27(1):27–39.CrossRefPubMed

Muraro SP, De Souza GF, Gallo SW, Da Silva BK, De Oliveira SD, Vinolo MAR, et al. Respiratory Syncytial Virus induces the classical ROS-dependent NETosis through PAD-4 and necroptosis pathways activation. Sci Rep. 2018;8(1):1–12.ADSCrossRef

10.

Alassaf N, Attia H. Autophagy and necroptosis in cisplatin-induced acute kidney injury: recent advances regarding their role and therapeutic potential. Front Pharmacol. 2023;14(January).

11.

Tang C, Cai J, Yin XM, Weinberg JM, Venkatachalam MA, Dong Z. Mitochondrial quality control in kidney injury and repair. Nat Rev Nephrol [Internet]. 2021;17(5):299–318. https://doi.org/10.1038/s41581-020-00369-0.

12.

Zhang Y, Su SS, Zhao S, Yang Z, Zhong CQ, Chen X et al. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun [Internet]. 2017;8(May 2016):1–14. https://doi.org/10.1038/ncomms14329.

13.

Fan Y, Lu J, Yu Z, Qu X, Guan S. 1,3-Dichloro-2-propanol-induced renal tubular cell necroptosis through the ROS/RIPK3/MLKL pathway. J Agric Food Chem. 2022;70(35):10847–57.CrossRefPubMed

14.

Al Shahrani M, Chandramoorthy HC, Alshahrani M, Abohassan M, Eid RA, Ravichandran K, et al. Cassia auriculata leaf extract ameliorates diabetic nephropathy by attenuating autophagic necroptosis via RIP-1/RIP-3-p-p38MAPK signaling. J Food Biochem. 2021;45(7):1–12.CrossRef

15.

Ren Q, Guo F, Tao S, Huang R, Ma L, Fu P. Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice. Biomedicine and Pharmacotherapy [Internet]. 2020;122(37):109772. https://doi.org/10.1016/j.biopha.2019.109772.

16.

Wu W, Wang X, Yu X, Lan HY. Smad3 signatures in renal inflammation and fibrosis. Int J Biol Sci. 2022;18(7):2795–806.CrossRefPubMedPubMedCentral

17.

Zhang W, Zheng X, Gong Y, Jiang T, Qiu J, Wu X et al. VX-11e protects articular cartilage and subchondral bone in osteoarthritis by inhibiting the RIP1/RIP3/MLKL and MAPK signaling pathways. Bioorg Chem [Internet]. 2022;120(January):105632. https://doi.org/10.1016/j.bioorg.2022.105632.

18.

Abd El-Aal SA, AbdElrahman M, Reda AM, Afify H, Ragab GM, El-Gazar AA et al. Galangin mitigates DOX-induced cognitive impairment in rats: Implication of NOX-1/Nrf-2/HMGB1/TLR4 and TNF-α/MAPKs/RIPK/MLKL/BDNF. Neurotoxicology [Internet]. 2022;92:77–90. https://doi.org/10.1016/j.neuro.2022.07.005.

19.

Sipieter F, Cappe B, Leray A, De Schutter E, Bridelance J, Hulpiau P et al. Characteristic ERK1/2 signaling dynamics distinguishes necroptosis from apoptosis. iScience. 2021;24(9).

20.

Hu W, Wu X, Yu D, Zhao L, Zhu X, Li X et al. Regulation of JNK signaling pathway and RIPK3/AIF in necroptosis-mediated global cerebral ischemia/reperfusion injury in rats. Exp Neurol [Internet]. 2020;331(June):113374. https://doi.org/10.1016/j.expneurol.2020.113374.

21.

Zhao Y, Li X, Wang F, Huang S, Du H, Li S, et al. Network Pharmacology and Experimental Verification Strategies to illustrate the mechanism of Jian-Pi-Yi-Shen Formula in suppressing epithelial–mesenchymal transition. Front Pharmacol. 2022;13(May):1–12.

22.

Liu X, Liu S, Zhang B, Luo D, Huang S, Wang F et al. Jian-Pi-Yi-Shen Formula Alleviates Chronic Kidney Disease in Two Rat Models by Modulating QPRT/NAD+/SIRT3/Mitochondrial Dynamics Pathway. Evidence-based Complementary and Alternative Medicine. 2021;2021.

23.

He R, Liu J, Chen Y, Liao Y, Wang Y, Jin X et al. A Chinese Medicine Compound Alleviates Cisplatin-Induced Acute Kidney Injury via Its Antiapoptosis and Anti-Inflammation Effects in Mice. Evidence-based Complementary and Alternative Medicine. 2022;2022.

24.

Zhou F, Zou X, Zhang J, Wang Z, Yang Y, Wang D. Jian-Pi-Yi-Shen Formula ameliorates oxidative stress, inflammation, and apoptosis by activating the Nrf2 Signaling in 5/6 nephrectomized rats. Front Pharmacol. 2021;12(March):1–12.

25.

Wei W, Wu X, Li J. Dosage issues in pharmacological experimental design in experimental methodology of Pharmacology. China: Academic; 2010. pp. 69–74.

26.

Lu Q, Wang M, Gui Y, Hou Q, Gu M, Liang Y et al. Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis. Cell Death Dis [Internet]. 2020;11(5). https://doi.org/10.1038/s41419-020-2539-4.

27.

Shi L, Song Z, Li C, Deng F, Xia Y, Huang J et al. HDAC6 inhibition alleviates ischemia- and Cisplatin-Induced Acute kidney Injury by promoting Autophagy. Cells. 2022;11(24).

28.

Blainey P, Krzywinski M, Altman N. Points of significance: replication. Nat Methods. 2014;11(9):879–80.CrossRefPubMed

29.

Fan X, Xu X, Wu X, Xia R, Gao F, Zhang Q et al. The protective effect of DNA aptamer on osteonecrosis of the femoral head by alleviating TNF-α-mediated necroptosis via RIP1/RIP3/MLKL pathway. J Orthop Translat [Internet]. 2022;36(February):44–51. https://doi.org/10.1016/j.jot.2022.07.001.

30.

Ciarimboli G, Ludwig T, Lang D, Pavenstädt H, Koepsell H, Piechota HJ, et al. Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005;167(6):1477–84.CrossRefPubMedPubMedCentral

31.

Kong MJ, Han SJ, Kim JI, Park JW, Park KM. Mitochondrial NADP+-dependent isocitrate dehydrogenase deficiency increases cisplatin-induced oxidative damage in the kidney tubule cells article. Cell Death Dis [Internet]. 2018;9(5). https://doi.org/10.1038/s41419-018-0537-6.

32.

Ortega-Domínguez B, Aparicio-Trejo OE, García-Arroyo FE, León-Contreras JC, Tapia E, Molina-Jijón E, et al. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic. Food Chem Toxicol. 2017;107:373–85.CrossRefPubMed

33.

Shen D, Guo M, Geng X, Yu J, Zhang Z, Lin J, et al. Magnesium Lithospermate B protects against Cisplatin-Induced Acute kidney Injury via alleviating mitochondrial dysfunction. Drug Des Devel Ther. 2022;16(January):2293–304.CrossRefPubMedPubMedCentral

34.

Zhou M, Dai Y, Ma Y, Yan Y, Hua M, Gao Q et al. Article Protective effects of Liquiritigenin against Cisplatin-Induced Nephrotoxicity via NRF2/SIRT3-Mediated improvement of mitochondrial function. Molecules. 2022;27(12).

35.

Kim JS, Kim KS, Son JY, Kim HR, Park JH, Lee SH et al. Protective effects of Dendropanax morbifera against cisplatin-induced nephrotoxicity without altering chemotherapeutic efficacy. Antioxidants. 2019;8(8).

36.

Almaghrabi OA. Molecular and biochemical investigations on the effect of quercetin on oxidative stress induced by cisplatin in rat kidney. Saudi J Biol Sci [Internet]. 2015;22(2):227–31. https://doi.org/10.1016/j.sjbs.2014.12.008.

37.

Manohar S, Leung N. Cisplatin nephrotoxicity: a review of the literature. J Nephrol. 2018;31(1):15–25.CrossRefPubMed

38.

Gwon MG, Gu H, Leem J, Park KK. Protective effects of 6-shogaol, an active compound of ginger, in a murine model of cisplatin-induced acute kidney injury. Molecules. 2021;26(19).

39.

Xiao X, Du C, Yan Z, Shi Y, Duan H, Ren Y. Inhibition of necroptosis attenuates kidney inflammation and interstitial Fibrosis Induced by Unilateral Ureteral obstruction. Am J Nephrol. 2017;46(2):131–8.CrossRefPubMed

40.

Rungelrath V, Kobayashi SD, DeLeo FR. Neutrophils in innate immunity and systems biology-level approaches. Wiley Interdiscip Rev Syst Biol Med. 2020;12(1):1–30.CrossRef

41.

Wu Y, Yang B. Erythropoietin Receptor/β common receptor: a shining light on acute kidney Injury Induced by Ischemia-Reperfusion. Front Immunol. 2021;12(June):1–11.

42.

Chen X, Wei W, Li Y, Huang J, Ci X. Hesperetin relieves cisplatin-induced acute kidney injury by mitigating oxidative stress, inflammation and apoptosis. Chem Biol Interact [Internet]. 2019;308(February):269–78. https://doi.org/10.1016/j.cbi.2019.05.040.

43.

Zhao X, Shi X, Liu Q, Li X. Tea polyphenols alleviates acetochlor-induced apoptosis and necroptosis via ROS/MAPK/NF-κB signaling in Ctenopharyngodon idellus kidney cells. Aquatic Toxicology [Internet]. 2022;246(November 2021):106153. https://doi.org/10.1016/j.aquatox.2022.106153.

44.

Miao Z, Miao Z, Shi X, Wu H, Yao Y, Xu S. The antagonistic effect of selenium on lead-induced apoptosis and necroptosis via P38/JNK/ERK pathway in chicken kidney. Ecotoxicol Environ Saf [Internet]. 2022;231(January):113176. https://doi.org/10.1016/j.ecoenv.2022.113176.

Title: JianPiYiShen formula prevents cisplatin-induced acute kidney injury in mice by improving necroptosis through MAPK pathway
Authors: Zhongtang Li
Riming He
Jiahui Liu
Xiaoming Jin
Beibei Jiang
Yunlan Lao
Shudong Yang
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Acute Kidney Injury
Acute Kidney Injury
Published in: BMC Complementary Medicine and Therapies / Issue 1/2024
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-024-04366-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

JianPiYiShen formula prevents cisplatin-induced acute kidney injury in mice by improving necroptosis through MAPK pathway

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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