Summary
Danshen, an efficacious agent for cardiovascular diseases, has been found to play an essential role in kidney injury. In the present study, the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model. Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment. A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity. The mice were sacrificed 72 h after cisplatin intoxication. Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed. Histopathological changes of kidney tissues were detected using HE staining. Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected. Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting. The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice. Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin. Moreover, Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues. Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice. It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice, which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hoek J, Bloemendal KM, van der Velden LA, et al. Nephrotoxicity as a dose-limiting factor in a high-dose cisplatin-based chemoradiotherapy regimen for head and neck carcinomas. Cancers, 2016,8(2):21
Latcha S, Jaimes EA, Patil S, et al. Long-term renal outcomes after cisplatin treatment. Clin J Am Soc Nephrol, 2016,11(7):1173–1179
Ries F, Klastersky J. Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. Am J Kidney Dis, 1986,8(5):368–379
Arunkumar PA, Viswanatha GL, Radheshyam N, et al. Science behind cisplatin-induced nephrotoxicity in humans: a clinical study. Asian Pac J Trop Biomed, 2012,2(8): 640–644
Miller RP, Tadagavadi RK, Ramesh G, et al. Mechanisms of cisplatin nephrotoxicity. Toxins, 2010,2(11):2490–2518
Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol, 2009,61(3):223–242
Santos NA, Catao CS, Martins NM, et al. Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol, 2007,81(7):495–504
Lv Q, Yao Y, Wang W, et al. Biliverdin protects against cisplatin-induced apoptosis of renal tubular epithelial cells. J Huazhong Univ Sci Technol Med Sci, 2016,36(1):48–52
Liu M, Grigoryev DN, Crow MT, et al. Transcription factor Nrf2 is protective during ischemic and nephrotoxic acute kidney injury in mice. Kidney Int, 2009,76(3): 277–285
Aleksunes LM, Goedken MJ, Rockwell CE, et al. Transcriptional regulation of renal cytoprotective genes by Nrf2 and its potential use as a therapeutic target to mitigate cisplatin-induced nephrotoxicity. J Pharmacol Exp Ther, 2010,335(1):2–12
Xu L, Shen P, Bi Y, et al. Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis. Int Immunopharmacol, 2016,38:385–394
Yin D, Yin J, Yang Y, et al. Renoprotection of Danshen Injection on streptozotocin-induced diabetic rats, associated with tubular function and structure. J Ethnopharmacol, 2014,151(1):667–674
Lu X, Jin Y, Ma L, et al. Danshen (Radix Salviae Miltiorrhizae) reverses renal injury induced by myocardial infarction. J Tradit Chin Med, 2015,35(3):306–311
Guan S, Ma J, Zhang Y, et al. Danshen (Salvia miltiorrhiza) injection suppresses kidney injury induced by iron overload in mice. PLoS One, 2013,8(9):e74318
Li L, Zhang Y, Ma J, et al. Salvia miltiorrhiza injection ameliorates renal damage induced by lead exposure in mice. Scientific World Journal, 2014,2014:572697
Kang DG, Oh H, Sohn EJ, et al. Lithospermic acid B isolated from Salvia miltiorrhiza ameliorates ischemia/reperfusion-induced renal injury in rats. Life Sci, 2004,75(15):1801–1816
Zou C, Lu F, Mao W, et al. Chinese herbal medicine Danshen formulations for preventing renal disease in Henoch-Schonlein Purpura: a systematic review and meta-analysis. J Altern Complement Med, 2012,18(4):394–401
Jin J, Li M, Zhao Z, et al. Protective effect of Wuzhi tablet (Schisandra sphenanthera extract) against cisplatin-induced nephrotoxicity via Nrf2-mediated defense response. Phytomedicine, 2015,22(5):528–535
Darwish MA, Abo-Youssef AM, Khalaf MM, et al. Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation. J Biochem Mol Toxic, 2016,31(1):1–9
Shelton LM, Park BK, Copple IM. Role of Nrf2 in protection against acute kidney injury. Kidney Int, 2013,84(6): 1090–1095
Noel S, Hamad A, Rabb H. Reviving the promise of transcription factor Nrf2-based therapeutics for kidney diseases. Kidney Int, 2015,88(6):1217–1218
Cornejo P, Vargas R, Videla LA. Nrf2-regulated phase-II detoxification enzymes and phase-III transporters are induced by thyroid hormone in rat liver. Biofactors, 2013,39(5):514–521
Shiraishi F, Curtis LM, Truong L, et al. Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. Am J Physiol Renal Physiol, 2000,278(5):F726–F736
Oh GS, Kim HJ, Choi JH, et al. Pharmacological activation of NQO1 increases NAD+ levels and attenuates cisplatin-mediated acute kidney injury in mice. Kidney Int, 2014,85(3):547–560
Lee SE, Jeong SI, Yang H, et al. Extract of Salvia miltiorrhiza (Danshen) induces Nrf2-mediated heme oxygenase-1 expression as a cytoprotective action in RAW 264.7 macrophages. J Ethnopharmacol, 2012,139(2):541–548
Zhou J, Qu X, Li Z, et al. Salvianolic acid B attenuates toxin-induced neuronal damage via Nrf2-dependent glial cells-mediated protective activity in Parkinson's disease models. PLoS One, 2014,9(7):e101668
Yu J, Wang L, Akinyi M, et al. Danshensu protects isolated heart against ischemia reperfusion injury through activation of Akt/ERK1/2/Nrf2 signaling. Int J Clin Exp Med, 2015,8(9):14793–14804
Chong CM, Zhou ZY, Razmovski-Naumovski V, et al. Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish. Neurosci Lett, 2013,543:121–125
Zhang Y, Jiang P, Ye M, et al. Tanshinones: sources, pharmacokinetics and anti-cancer activities. Int J Mol Sci, 2012,13(10):13621–13666
Author information
Authors and Affiliations
Corresponding author
Additional information
This project was supported by grants from the National Natural Science Foundation of China (Nos. 81202985 and 81573686).
Rights and permissions
About this article
Cite this article
Cao, Ss., Yan, M., Hou, Zy. et al. Danshen modulates Nrf2-mediated signaling pathway in cisplatin-induced renal injury. CURR MED SCI 37, 761–765 (2017). https://doi.org/10.1007/s11596-017-1801-1
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-017-1801-1