Effect of idebenone on bone marrow mesenchymal stem cells in vitro

Zhang,Jiahui; Zhang,Jun; Li,Tao; Zhang,Nannan; Tang,Shengnan; Tao,Zehua; Zhou,Xiaohe; Sun,Xiaochun; Chen,Huabiao

doi:10.3892/mmr.2018.8506

Effect of idebenone on bone marrow mesenchymal stem cells in vitro

Authors:
- Jiahui Zhang
- Jun Zhang
- Tao Li
- Nannan Zhang
- Shengnan Tang
- Zehua Tao
- Xiaohe Zhou
- Xiaochun Sun
- Huabiao Chen
View Affiliations

Affiliations: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China, Clinical Laboratory, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: January 26, 2018 https://doi.org/10.3892/mmr.2018.8506
Pages: 5376-5383

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In recent years, stem cell research has continued to benefit from its crossover with chemistry, particularly the investigation of small molecular drugs modulating specific targets to regulate stem cell fate. Idebenone (IDB) is a yellow crystalline powder that is used in the treatment of chronic cerebrovascular diseases. The objective of the present study was to examine whether IDB had an influence on bone marrow‑derived mesenchymal stem cells (BMSCs) extracted from the bone marrow of Sprague‑Dawley rats. The effects of IDB on cell proliferation, cell cloning and migration were investigated. Cell cycle, apoptosis, DAPI nuclear staining and senescence‑associated β‑galactosidase (SA‑β‑gal) staining were also examined. The results revealed that IDB at suitable concentrations enhanced cell cloning capacity, promoted the proliferation of BMSCs, delayed cellular senescence, and inhibited cell apoptosis and migration. Western blot analysis indicated that IDB increased the expression of B‑cell lymphoma 2 (Bcl‑2), signal transducer and activator of transcription‑3, Nanog, octamer‑binding transcription factor 4, E‑cadherin, proliferating cell nuclear antigen, cyclinD1 and cyclinD3, and decreased the expression of Bcl‑2‑associated X protein, cleaved caspase‑3, N‑cadherin, vimentin and α‑smooth muscle actin. In conclusion, these experiments confirmed that IDB in low doses had no toxic effect and may exert protective effects on BMSCs.

View Figures

View References

1	Dong KK, Damaghi N, Kibitel J, Canning MT, Smiles KA and Yarosh DB: A comparison of the relative antioxidant potency of L-ergothioneine and idebenone. J Cosmet Dermatol. 6:183–188. 2007. View Article : Google Scholar : PubMed/NCBI
2	Schulz JB, Di Prospero NA and Fischbeck K: Clinical experience with high-dose IDB in Friedreich ataxia. J Neurol. 256 Suppl 1:S42–S45. 2009. View Article : Google Scholar
3	Ahmed MA: Neuroprotective effects of idebenone against pilocarpine-induced seizures: Modulation of antioxidant status, DNA damage and Na(+), K (+)-ATPase activity in rat hippocampus. Neurochem Res. 39:394–402. 2014. View Article : Google Scholar : PubMed/NCBI
4	Gutzmann H, Kühl KP, Hadler D and Rapp MA: Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: Results of a randomized, double-blind, parallel-group multicenter study. Pharmacopsychiatry. 35:12–18. 2002. View Article : Google Scholar : PubMed/NCBI
5	Parkinson MH, Schulz JB and Giunti P: Co-enzyme Q10 and idebenone use in Friedreich's ataxia. J Neurochem. 126 Suppl 1:S125–S141. 2013. View Article : Google Scholar
6	Rustin P, von Kleist-Retzow JC, Chantrel-Groussard K, Sidi D, Munnich A and Rötig A: Effect of idebenone on cardiomyopathy in Friedreich's ataxia: A preliminary study. Lancet. 354:477–479. 1999. View Article : Google Scholar : PubMed/NCBI
7	Rustin P, Rötig A, Munnich A and Sidi D: Heart hypertrophy and function are improved by idebenone in Friedreich's ataxia. Free Radic Res. 36:467–469. 2002. View Article : Google Scholar : PubMed/NCBI
8	Artuch R, Aracil A, Mas A, Colomé C, Rissech M, Monrós E and Pineda M: Friedreich's ataxia: Idebenone treatment in early stage patients. Neuropediatrics. 33:190–193. 2002. View Article : Google Scholar : PubMed/NCBI
9	Hausse AO, Aggoun Y, Bonnet D, Sidi D, Munnich A, Rötig A and Rustin P: idebenone and reduced cardiac hypertrophy in Friedreich's ataxia. Heart. 87:346–349. 2002. View Article : Google Scholar : PubMed/NCBI
10	La Pean A, Jeffries N, Grow C, Ravina B and Di Prospero NA: Predictors of progression in patients with Friedreich ataxia. Mov Disord. 23:2026–2032. 2008.PubMed/NCBI
11	Di Prospero NA, Baker A, Jeffries N and Fischbeck KH: Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: A randomised, placebo-controlled trial. Lancet Neurol. 6:878–886. 2007. View Article : Google Scholar : PubMed/NCBI
12	Tonon C and Lodi R: Idebenone in Friedreich's ataxia. Expert Opin Pharmacother. 9:2327–2337. 2008. View Article : Google Scholar : PubMed/NCBI
13	Pineda M, Arpa J, Montero R, Aracil A, Domínguez F, Galván M, Mas A, Martorell L, Sierra C, Brandi N, et al: idebenone treatment in paediatric and adult patients with Friedreich ataxia: Long-term follow-up. Eur J Paediatr Neurol. 12:470–475. 2008. View Article : Google Scholar : PubMed/NCBI
14	Riazi A, Cano SJ, Cooper JM, Bradley JL, Schapira AH and Hobart JC: Coordinating outcomes measurement in ataxia research: Do some widely used generic rating scales tick the boxes? Mov Disord. 21:1396–1403. 2006. View Article : Google Scholar : PubMed/NCBI
15	Zhu GR, Zhou XY, Lu H, Zhou JW, Li AP, Xu W, Li JY and Wang CY: Human bone marrow mesenchymal stem cells express multiple hematopoietic growth factors. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 11:115–119. 2003.(In Chinese). PubMed/NCBI
16	da Silva Meirelles L, Sand TT, Harman RJ, Lennon DP and Caplan AI: MSC frequency correlates with blood vessel density in equine adipose tissue. Tissue Eng Part A. 15:221–229. 2009. View Article : Google Scholar : PubMed/NCBI
17	Antunes MA, Abreu SC, Cruz FF, Teixeira AC, Lopes-Pacheco M, Bandeira E, Olsen PC, Diaz BL, Takyia CM, Freitas IP, et al: Effects of different mesenchymal stromal cell sources and delivery routes in experimental emphysema. Respir Res. 15:1182014. View Article : Google Scholar : PubMed/NCBI
18	Barry FP and Murphy JM: Mesenchymal stem cells: Clinical applications and biological characterization. Int J Biochem Cell Biol. 36:568–584. 2004. View Article : Google Scholar : PubMed/NCBI
19	Yang ZX, Han ZB, Ji YR, Wang YW, Liang L, Chi Y, Yang SG, Li LN, Luo WF, Li JP, et al: CD106 identifies a subpopulation of mesenchymal stem cells with unique immunomodulatory properties. PLoS One. 8:e593542013. View Article : Google Scholar : PubMed/NCBI
20	Burk J, Gittel C, Heller S, Pfeiffer B, Paebst F, Ahrberg AB and Brehm W: Gene expression of tendon markers in mesenchymal stromal cells derived from different sources. BMC Res Notes. 7:8262014. View Article : Google Scholar : PubMed/NCBI
21	Xu H, Qian H, Zhu W, Zhang X, Yan Y, Mao F, Wang M, Xu H and Xu W: Mesenchymal stem cells relieve fibrosis of Schistosoma japonicum-induced mouse liver injury. Exp Biol Med (Maywood). 237:585–592. 2012. View Article : Google Scholar : PubMed/NCBI
22	Farris P: Idebenone, green tea, and Coffeeberry extract: New and innovative antioxidants. Dermatol Ther. 20:322–329. 2007. View Article : Google Scholar : PubMed/NCBI
23	McDaniel DH, Neudecker BA, DiNardo JC, Lewis JA II and Maibach HI: Idebenone: A new antioxidant-Part I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants. J Cosmet Dermatol. 4:10–17. 2005. View Article : Google Scholar : PubMed/NCBI
24	Haginoya K, Miyabayashi S, Kikuchi M, Kojima A, Yamamoto K, Omura K, Uematsu M, Hino-Fukuyo N, Tanaka S and Tsuchiya S: Efficacy of idebenone for respiratory failure in a patient with Leigh syndrome: A long-term follow-up study. J Neurol Sci. 278:112–114. 2009. View Article : Google Scholar : PubMed/NCBI
25	Meier T and Buyse G: Idebenone: An emerging therapy for Friedreich ataxia. J Neurol. 256 Suppl 1:S25–S30. 2009. View Article : Google Scholar
26	Zs-Nagy I: Chemistry, toxicology, pharmacology and pharmacokinetics of idebenone: A review. Arch Gerontol Geriatr. 11:177–186. 1990. View Article : Google Scholar : PubMed/NCBI
27	Gillis JC, Benefield P and McTavish D: Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders. Drugs Aging. 5:133–152. 1994. View Article : Google Scholar : PubMed/NCBI
28	Suno M and Nagaoka A: Inhibition of lipid peroxidation by a novel compound (CV-2619) in brain mitochondria and mode of action of the inhibition. Biochem Biophys Res Commun. 125:1046–1052. 1984. View Article : Google Scholar : PubMed/NCBI
29	Deng W, Han Q, Liao L, You S, Deng H and Zhao RC: Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol. 24:458–463. 2005. View Article : Google Scholar : PubMed/NCBI
30	Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V and Uccelli A: Human mesenchymal stem cells modulate B-cell functions. Blood. 107:367–372. 2006. View Article : Google Scholar : PubMed/NCBI
31	Yin Z, Chen D, Hu F, Ruan Y, Li J, Wang L, Xiang Y, Xie L, Wang X, Ichim TE, et al: Cotransplantation with xenogenetic neonatal porcine sertoli cells significantly prolongs islet allograft survival in nonimmunosuppressive rats. Transplantation. 88:339–345. 2009. View Article : Google Scholar : PubMed/NCBI
32	Dufour JM, Dass B, Halley KR, Korbutt GS, Dixon DE and Rajotte RV: Sertoli cell line lacks the immunoprotective properties associated with primary Sertoli cells. Cell Transplant. 17:525–534. 2008. View Article : Google Scholar : PubMed/NCBI