Melatonin protects MG63 osteoblast-like cells from hydrogen peroxide-induced cytotoxicity by maintaining mitochondrial function

She,Fei; Wang,Wenbo; Wang,Yan; Tang,Peifu; Wei,Junqiang; Chen,Hua; Zhang,Boxun

doi:10.3892/mmr.2013.1832

Melatonin protects MG63 osteoblast-like cells from hydrogen peroxide-induced cytotoxicity by maintaining mitochondrial function

Authors:
- Fei She
- Wenbo Wang
- Yan Wang
- Peifu Tang
- Junqiang Wei
- Hua Chen
- Boxun Zhang
View Affiliations

Affiliations: Department of Orthopaedic Surgery, General Hospital of the Chinese People's Liberation Army, Beijing 100853, P.R. China, Department of Endocrinology, General Hospital of the Chinese People's Liberation Army, Beijing 100853, P.R. China
Published online on: November 28, 2013 https://doi.org/10.3892/mmr.2013.1832
Pages: 493-498

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

Osteoporosis is a bone disease that has been connected with reactive oxygen species (ROS)‑induced cytotoxicity. Mitochondrial dysfunction may be involved in the mechanism underlying ROS‑induced cytotoxicity. It has been demonstrated that melatonin may exert cytoprotective effects by improving mitochondrial energetics and functions in several models of oxidative damage. In the present study, the MG63 osteoblast-like cell line was exposed to different concentrations of hydrogen peroxide (H2O2; 0, 100, 200, 400 or 800 µM) for 8 h, and 200 or 400 µM H2O2 for various periods of time (0.5, 4, 8 or 12 h). Results showed that H2O2 significantly reduced cell viability, increased the release of lactate dehydrogenase, increased the levels of ROS and malondialdehyde, reduced the concentration of adenosine-5'-triphosphate, disrupted the mitochondrial membrane potential (ΔΨm) and decreased the mitochondrial DNA copy number in MG63 cells. However, pretreatment with melatonin effectively decreased all of these H2O2-induced changes in cytotoxicity and mitochondrial dysfunction in MG63 cells. The protective effects of melatonin may be attributed to its ability to maintain mitochondrial function in H2O2‑treated cells. This study suggests that melatonin is a potential pharmacological agent for preventing ROS‑induced bone loss in diseases such as osteoporosis.

View Figures

View References

1	Sandhu SK and Hampson G: The pathogenesis, diagnosis, investigation and management of osteoporosis. J Clin Pathol. 64:1042–1050. 2011. View Article : Google Scholar : PubMed/NCBI
2	Choi EM: Magnolol protects osteoblastic MC3T3-E1 cells against antimycin A-induced cytotoxicity through activation of mitochondrial function. Inflammation. 35:1204–1212. 2012. View Article : Google Scholar : PubMed/NCBI
3	Xu ZS, Wang XY, Xiao DM, et al: Hydrogen sulfide protects MC3T3-E1 osteoblastic cells against H₂O₂-induced oxidative damage-implications for the treatment of osteoporosis. Free Radic Biol Med. 50:1314–1323. 2011. View Article : Google Scholar : PubMed/NCBI
4	Park BG, Yoo CI, Kim HT, Kwon CH and Kim YK: Role of mitogen-activated protein kinases in hydrogen peroxide-induced cell death in osteoblastic cells. Toxicology. 215:115–125. 2005. View Article : Google Scholar : PubMed/NCBI
5	Lee HC and Wei YH: Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging. Exp Biol Med (Maywood). 232:592–606. 2007.PubMed/NCBI
6	Raha S and Robinson BH: Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci. 25:502–508. 2000. View Article : Google Scholar : PubMed/NCBI
7	Choi EM: Deoxyactein isolated from Cimicifuga racemosa protects osteoblastic MC3T3-E1 cells against antimycin A-induced cytotoxicity. J Appl Toxicol. 33:488–494. 2013.
8	Slominski A, Fischer TW, Zmijewski MA, et al: On the role of melatonin in skin physiology and pathology. Endocrine. 27:137–148. 2005. View Article : Google Scholar : PubMed/NCBI
9	Bubenik GA: Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci. 47:2336–2348. 2002. View Article : Google Scholar : PubMed/NCBI
10	Jimenez-Jorge S, Jimenez-Caliani AJ, Guerrero JM, et al: Melatonin synthesis and melatonin-membrane receptor (MT1) expression during rat thymus development: role of the pineal gland. J Pineal Res. 39:77–83. 2005. View Article : Google Scholar : PubMed/NCBI
11	Rosenstein RE, Pandi-Perumal SR, Srinivasan V, Spence DW, Brown GM and Cardinali DP: Melatonin as a therapeutic tool in ophthalmology: implications for glaucoma and uveitis. J Pineal Res. 49:1–13. 2010.PubMed/NCBI
12	Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M and Maestroni JM: Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res. 28:193–202. 2000. View Article : Google Scholar : PubMed/NCBI
13	Rajaratnam SM, Middleton B, Stone BM, Arendt J and Dijk DJ: Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans. J Physiol. 561:339–351. 2004. View Article : Google Scholar
14	Arendt J and Skene DJ: Melatonin as a chronobiotic. Sleep Med Rev. 9:25–39. 2005. View Article : Google Scholar
15	Armstrong SM: Melatonin and circadian control in mammals. Experientia. 45:932–938. 1989. View Article : Google Scholar : PubMed/NCBI
16	Deacon S and Arendt J: Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans. Brain Res. 688:77–85. 1995. View Article : Google Scholar
17	Srinivasan V, Spence WD, Pandi-Perumal SR, Zakharia R, Bhatnagar KP and Brzezinski A: Melatonin and human reproduction: shedding light on the darkness hormone. Gynecol Endocrinol. 25:779–785. 2009. View Article : Google Scholar : PubMed/NCBI
18	Guerrero JM and Reiter RJ: Melatonin-immune system relationships. Curr Top Med Chem. 2:167–179. 2002. View Article : Google Scholar : PubMed/NCBI
19	Hardeland R, Poeggeler B, Niebergall R and Zelosko V: Oxidation of melatonin by carbonate radicals and chemiluminescence emitted during pyrrole ring cleavage. J Pineal Res. 34:17–25. 2003. View Article : Google Scholar : PubMed/NCBI
20	Coto-Montes A and Hardeland R: New vistas on oxidative damage and aging. Open Biol J. 3:39–52. 2010. View Article : Google Scholar
21	León J, Acuña-Castroviejo D, Escames G, Tan DX and Reiter RJ: Melatonin mitigates mitochondrial malfunction. J Pineal Res. 38:1–9. 2005.PubMed/NCBI
22	Klongpanichapak S, Phansuwan-Pujito P, Ebadi M and Govitrapong P: Melatonin protects SK-N-SH neuroblastoma cells from amphetamine-induced neurotoxicity. J Pineal Res. 43:65–73. 2007. View Article : Google Scholar : PubMed/NCBI
23	Duan Q, Wang Z, Lu T, Chen J and Wang X: Comparison of 6-hydroxylmelatonin or melatonin in protecting neurons against ischemia/reperfusion-mediated injury. J Pineal Res. 41:351–357. 2006. View Article : Google Scholar : PubMed/NCBI
24	Herrera F, Martin V, Garcia-Santos G, Rodriguez-Blanco J, Antolin I and Rodriguez C: Melatonin prevents glutamate-induced oxytosis in the HT22 mouse hippocampal cell line through an antioxidant effect specifically targeting mitochondria. J Neurochem. 100:736–746. 2007. View Article : Google Scholar
25	Chen LJ, Gao YQ, Li XJ, Shen DH and Sun FY: Melatonin protects against MPTP/MPP⁺-induced mitochondrial DNA oxidative damage in vivo and in vitro. J Pineal Res. 39:34–42. 2005. View Article : Google Scholar : PubMed/NCBI
26	Jou MJ, Peng TI, Yu PZ, et al: Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis. J Pineal Res. 43:389–403. 2007. View Article : Google Scholar : PubMed/NCBI
27	Tan DX, Manchester LC, Terron MP, Flores LJ and Reiter RJ: One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res. 42:28–42. 2007. View Article : Google Scholar : PubMed/NCBI
28	Reiter RJ, Tan DX, Jou MJ, Korkmaz A, Manchester LC and Paredes SD: Biogenic amines in the reduction of oxidative stress: melatonin and its metabolites. Neuro Endocrinol Lett. 29:391–398. 2008.PubMed/NCBI
29	Choi EM, Kim GH and Lee YS: Diazoxide protects against hydrogen peroxide-induced toxicity in the osteoblastic MC3T3-E1 cells. Eur J Pharmacol. 624:45–50. 2009. View Article : Google Scholar : PubMed/NCBI
30	López A, García JA, Escames G, et al: Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production. J Pineal Res. 46:188–198. 2009.PubMed/NCBI
31	Xu S, Zhong M, Zhang L, et al: Overexpression of Tfam protects mitochondria against beta-amyloid-induced oxidative damage in SH-SY5Y cells. FEBS J. 276:3800–3809. 2009. View Article : Google Scholar : PubMed/NCBI
32	Acuña Castroviejo D, Escames G, Carazo A, León J, Khaldy H and Reiter RJ: Melatonin, mitochondrial homeostasis and mitochondrial-related diseases. Curr Top Med Chem. 2:133–151. 2002.PubMed/NCBI
33	Xu S, Zhou Z, Zhang L, et al: Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons. Brain Res. 1311:189–196. 2010. View Article : Google Scholar : PubMed/NCBI
34	Escames G, López A, García JA, et al: The role of mitochondria in brain aging and the effects of melatonin. Curr Neuropharmacol. 8:182–193. 2010. View Article : Google Scholar : PubMed/NCBI
35	Vairetti M, Ferrigno A, Bertone R, et al: Exogenous melatonin enhances bile flow and ATP levels after cold storage and reperfusion in rat liver: implications for liver transplantation. J Pineal Res. 38:223–230. 2005. View Article : Google Scholar : PubMed/NCBI