Cisplatin is a highly effective antitumor agent whose clinical application is limited by its nephrotoxicity, which is associated with high mortality and morbidity rates. We aimed to study the protective role of silymarin and mesenchymal stem cells as a therapeutic tool of cisplatin nephrotoxicity.
Materials and Methods
We injected rats with cisplatin in a dose of 5 mg/kg body weight for 5 days to induce acute renal failure (ARF). Silymarin was administrated 6 hours before cisplatin injection and mesenchymal stem cells were injected 24 hours after cisplatin-induced ARF.
We assessed the ARF biochemically by elevation of kidney function tests and histopathologically by an alteration of the histological architecture of the renal cortex in the form of shrinkage of glomeruli, lobulated tufts and glomerular hypertrophy with narrowing capsular space. The tubules showed extensive tubular degeneration with cellular hyaline materials and debris in the lumen of the renal tubules. The renal blood vessels appeared sclerotic with marked thickened walls. When silymarin was given in different doses before cisplatin, it decreased the toxic effect of cisplatin in the kidney but sclerotic blood vessels remained. Injection of mesenchymal stem cells in rats with cisplatin-induced ARF improved the histopathological effects of cisplatin in renal tissues and kidney function tests were significantly improved.
There was a significant improvement in kidney function tests and renal histopathology by using silymarin as protective mechanism in cisplatin-induced ARF. Administration of mesenchymal stem cells denoted a more remarkable therapeutic effect in ARF.
Key Indexing Terms
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to The American Journal of the Medical Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Clinical development of platinum complexes in cancer therapy: an historical perspective and an update.Eur J Cancer. 1998; 34: 1522-1534
- Cisplatin nephrotoxicity.Semin Nephrol. 2003; 23: 460-464
- Acute renal failure: a practical update.Mayo Clin Proc. 2001; 76: 67-74
- Cisplatin nephrotoxicity: mechanisms and renoprotective strategies.Kidney Int. 2008; 73: 994-1007
- Mature results of a phase III randomized trial comparing concurrent chemo radiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck.Cancer. 2000; 88: 876-883
- Pharmacol Res. 2003; 47: 149-156
- Bone marrow plasticity revisited: protection or differentiation in the kidney tubule?.J Clin Invest. 2005; 115: 1705-1708
- Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects.Proc Natl Acad Sci. 2003; 100: 8407-8411
- Stem-cell therapy shows promise for horse soft-tissue injury, disease.Can Vet J. 2008; 50: 155-165
- L-methionine antagonism of cisplatinum nephrotoxicity.Toxicol Appl Pharmacol. 1990; 103: 1-15
- Dose-dependent protection by lipoic acid against cisplatininduced nephrotoxicity in rats: antioxidant defense system.PharmacolToxicol. 2000; 86: 234-241
- Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.).Integr CancerTher. 2007; 6: 146-157
- Effects of maternal exposure to diethylstilbestrol on the development of the reproductive system and thyroid function in male and female rat offspring.J Toxicol Sci. 2003; 28: 385-394
- Silymarin administration protects against cisplatin-induced nephrotoxicity in adult male albino rats. (Histological and immunohistochemical study).Egypt J Histol. 2010; 33: 683-691
- Therapeutic role of mesenchymal stem cells in cisplatin induced renal failure in adult male rats.Adv Biol Res. 2015; 9: 201-209
- Reactive bone marrow stromal cells attenuate systemic inflammation via sTNFR1.Mol Ther. 2010; 18: 1857-1864
- Simple and sensitive determination of urea in serum and urine.Clin Chem. 1992; 38: 619-623
- Principles and techniques.ClinicalChemistry. 2nd ed. Harper and Row, New York, USA1974: 543-548
- Involvement of the CDK2-E2F1 pathway in cisplatin cytotoxicity in vitro and in vivo.Am J Physiol Renal Physiol. 2007; 293: F52-F59
- Role of mesenchymal stem cell therapy in cisplatin induced nephrotoxicity in adult albino rats: ultrastructural & biochemical study.Acta Med Int. 2014; 1: 57-66
- Effect of selenium on cisplatin-induced nephrotoxicity in rats.Nephron Exp Nephrol. 2006; 104: e112-e122
- Ascorbic acid and alpha-tocopherol protect anticancer drug cisplatin induced nephrotoxicity in mice: a comparative study.Clin Chim Acta. 2007; 375: 82-86
- Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity.Biochem Pharmacol. 2007; 74: 477-487
- Protective effect of silymarin on cisplatin-induced nephrotoxicity in rats.Pak J Nutr. 2010; 9: 624-636
- Cell-based therapies in kidney disease.Kidney Int. 2013; 3: 364-367
- In search of adult renal stem cells.J Cell Mol Med. 2004; 4: 474-487
- Renal and bone marrow cells fuse after renal ischemic injury.J Am Soc Nephrol. 2007; 18: 3067-3077
- Reduces endothelial progenitor cell homing to activated (glomerular) endothelium in vitro and in vivo.Am J Physiol Renal Physiol. 2007; 293: F624-F630
- Fetal kidney stem cells ameliorate cisplatin induced acute renal failure and promote renal angiogenesis.World J Stem Cells. 2015; 7: 776-788
- Human adipose-derived mesenchymal stem cells repair cisplatin-induced acute kidney injury through antiapoptotic pathways.Exp Ther Med. 2015; 10: 468-476
- Mesenchymal stem cells therapy in acute renal failure: possible role of hepatocyte growth factor.J Stem Cell Res. 2011; : 1-3
- Mesenchymal stem cell therapy prevents interstitial fibrosis and tubular atrophy in a rat kidney allograft model.Stem Cells Dev. 2012; 21: 3125-3135
- Early modulation of inflammation by mesenchymal stem cell after acute kidney injury.Int Immunopharmacol. 2009; 9: 677-682
- Kidney-targeted transplantation of mesenchymal stem cells by ultrasound-targeted microbubble destruction promotes kidney repair in diabetic nephropathy in rats.Biomed Res Int. 2013; 2013: 526367
Published online: September 01, 2017
Accepted: August 9, 2017
Received in revised form: August 5, 2017
Received: March 21, 2017
☆The authors have no financial or other conflicts of interest to disclose.
© 2017 Southern Society for Clinical Investigation. Published by All rights reserved.