Abstract
Background:
The anti-aging property of β-D-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory and immunosuppressive agent was investigated on several determinants relative to the oxidative stress in an animal model.
Methods:
Sprague-Dawley rats were used for evaluating the safety and efficacy properties of M2000 on some oxidative stress enzymes, including the following: mitochondrial superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPX1), glutathione S-transferase (GST), myeloperoxidase (MPO), and inducible nitric oxide synthase (iNOS) gene expression by real-time PCR. Malondialdehyde (MDA), carbonyl protein (PCO) (the lipid and protein oxidation marker, respectively), and total antioxidant capacity (TAC) were tested in serum by biochemical analysis. In addition, cortisol as a steroid hormone was surveyed by chemiluminescence immunoassay after 12 weeks of M2000 consumption. The rats were sacrificed 3 months after daily oral administration of M2000.
Results:
Our findings revealed the favorable effects of M2000 on several antioxidant enzyme and gene expression, including SOD2, CAT, GPX1, and GST; however, our results were not statistically significant. Moreover, there was no significant difference in MDA and PCO as lipid and protein oxidation markers, TAC, and cortisol compared with the control group following M2000 consumption. A slight weight increase in the M2000-treated group was also observed.
Conclusions:
Our data showed the anti-aging property of M2000 as a novel designed non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property on various oxidative stress determinants.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Oboh G, Nwanna EE, Ibukun EO. Antioxidative properties and inhibition of some pro-oxidant induced lipid peroxidation by aqueous extract of two species of eggplants Solanum macrocarpon and Solanum melongena. Int J Nutr Metab 2013;5:88–97.Search in Google Scholar
2. Halliwell B, Gutteridge JM. Free radicals in biology and medicine. Fifth edition. Oxford: Oxford university press, 2015:200–1.10.1093/acprof:oso/9780198717478.001.0001Search in Google Scholar
3. McCord JM. Oxygen–derived free radicals in postischemic tissue injury. N Engl J Med 1985;312:159–63.10.1056/NEJM198501173120305Search in Google Scholar
4. Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 1994;344:721–4.10.1016/S0140-6736(94)92211-XSearch in Google Scholar
5. Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science 1996;273:59–63.10.1126/science.273.5271.59Search in Google Scholar PubMed PubMed Central
6. Sies H. Oxidative stress: introductory remarks. Oxidative stress 1985:1–8.10.1016/B978-0-12-642760-8.50005-3Search in Google Scholar
7. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19:257–67.10.2337/diacare.19.3.257Search in Google Scholar PubMed
8. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000;408:239–47.10.1038/35041687Search in Google Scholar PubMed
9. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44–84.10.1016/j.biocel.2006.07.001Search in Google Scholar PubMed
10. Tachon P. DNA single strand breakage by H2O2 and ferric or cupric ions: its modulation by histidine. Free Radic Res 1990;9:39–47.10.3109/10715769009148571Search in Google Scholar
11. Anandan R, Ganesan B, Obulesu T, Mathew S, Asha K, Lakshmanan P, et al. Antiaging effect of dietary chitosan supplementation on glutathione-dependent antioxidant system in young and aged rats. Cell Stress Chaperones 2013;18:121–5.10.1007/s12192-012-0354-2Search in Google Scholar PubMed PubMed Central
12. Sarban S, Kocyigit A, Yazar M, Isikan UE. Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis. Clin Biochem 2005;38:981–6.10.1016/j.clinbiochem.2005.08.003Search in Google Scholar PubMed
13. Goudarzvand M, Afraei S, Yaslianifard S, Ghiasy S, Sadri G, Kalvandi M, et al. Hydroxycitric acid ameliorates inflammation and oxidative stress in mouse models of multiple sclerosis. Neural Regen Res 2016;11:1610–6.10.4103/1673-5374.193240Search in Google Scholar
14. Javanbakht MH, Sadria R, Djalali M, Derakhshanian H, Hosseinzadeh P, Zarei M, et al. Soy protein and genistein improves renal antioxidant status in experimental nephrotic syndrome. Nefrologia 2014;34:483–90.Search in Google Scholar
15. Augustin W, Wiswedel I, Noack H, Reinheckel T, Reichelt O. Role of endogenous and exogenous antioxidants in the defence against functional damage and lipid peroxidation in rat liver mitochondria. Mol Cell Biochem 1997;174:199–205.10.1007/978-1-4615-6111-8_31Search in Google Scholar
16. Nagamma T, Ahmed S, Pai A, Mohan S, Chathuvedi A, Singh P. Evaluation of oxidative stress and antioxidant activity in pre and post hemodialysis in chronic renal failure patients from Western region of Nepal. Bangladesh J Med Sci 2013;13:40–4.10.3329/bjms.v13i1.14741Search in Google Scholar
17. Kakizawa S, Yamazawa T, Iino M. Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor by endogenous nitric oxide. Channels 2013;7:1–5.10.4161/chan.22555Search in Google Scholar
18. Ookawa H, Tonotani J. Organic electroluminescent element. Google Patents; 2010.Search in Google Scholar
19. Dorval J, Leblond V, Hontela A. Oxidative stress and loss of cortisol secretion in adrenocortical cells of rainbow trout (Oncorhynchus mykiss) exposed in vitro to endosulfan, an organochlorine pesticide. Aquat Toxicol 2003;63:229–41.10.1016/S0166-445X(02)00182-0Search in Google Scholar
20. Mirshafiey A, Cuzzocrea S, Rehm B, Mazzon E, Saadat F, Sotoude M. Treatment of experimental arthritis with M2000, a novel designed non-steroidal anti-inflammatory drug. Scand J Immunol 2005;61:435–41.10.1111/j.1365-3083.2005.01594.xSearch in Google Scholar PubMed
21. Azizi G, Mirshafiey A. Imatinib mesylate: an innovation in treatment of autoimmune diseases. Recent Pat Inflamm Allergy Drug Discov 2013;7:259–67.10.2174/1872213X113079990021Search in Google Scholar PubMed
22. Naddafi F, Reza Haidari M, Azizi G, Sedaghat R, Mirshafiey A. Novel therapeutic approach by nicotine in experimental model of multiple sclerosis. Innov Clin Neurosci 2013;10:20–5.Search in Google Scholar
23. Tyrakowska B, Lemańska K, Szymusiak H, Borkowski T, Rietjens I. Modified TEAC test for determination of the antioxidant properties of dietary polyphenolic compounds over a wide pH range. Polish J Food Nutr Sci 2003;12:141–8.Search in Google Scholar
24. Ozgen M, Reese RN, Tulio AZ, Scheerens JC, Miller AR. Modified 2, 2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method to measure antioxidant capacity of selected small fruits and comparison to ferric reducing antioxidant power (FRAP) and 2, 2ß°-diphenyl-1-picrylhydrazyl (DPPH) methods. J Agric Food Chem 2006;54:1151–7.10.1021/jf051960dSearch in Google Scholar PubMed
25. Almajano MP, Carbo R, Jiménez JA, Gordon MH. Antioxidant and antimicrobial activities of tea infusions. Food Chem 2008;108:55–63.10.1016/j.foodchem.2007.10.040Search in Google Scholar
26. Campos C, Guzmán R, López-Fernández E, Casado Á. Evaluation of the copper (II) reduction assay using bathocuproinedisulfonic acid disodium salt for the total antioxidant capacity assessment: the CUPRAC–BCS assay. Anal Biochem 2009;392:37–44.10.1016/j.ab.2009.05.024Search in Google Scholar PubMed
27. Banerjee B, Seth V, Bhattacharya A, Pasha S, Chakraborty A. Biochemical effects of some pesticides on lipid peroxidation and free-radical scavengers. Toxicol Lett 1999;107:33–47.10.1016/S0378-4274(99)00029-6Search in Google Scholar
28. Stadtman ER, Levine RL. Protein oxidation. Ann N Y Acad Sci 2000; 899:191–208.10.1111/j.1749-6632.2000.tb06187.xSearch in Google Scholar PubMed
29. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010;49:1603–16.10.1016/j.freeradbiomed.2010.09.006Search in Google Scholar PubMed PubMed Central
30. Mirshafiey A, Matsuo H, Nakane S, Rehm BH, Koh C-S, Miyoshi S. Novel immunosuppressive therapy by M2000 in experimental multiple sclerosis. Immunopharmacol Immunotoxicol 2005;27:255–65.10.1081/IPH-200067751Search in Google Scholar
31. Mirshafiey A, Rehm B, Sotoude M, Razavi A, Abhari RS, Borzooy Z. Therapeutic approach by a novel designed anti-inflammatory drug, M2000, in experimental immune complex glomerulonephritis. Immunopharmacol Immunotoxicol 2007;29:49–61.10.1080/08923970701282387Search in Google Scholar PubMed
32. Şener G, Ekşioğlu-Demiralp E, Çetiner M, Ercan F, Yeğen BÇ. β-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. Eur J Pharmacol 2006;542:170–8.10.1016/j.ejphar.2006.02.056Search in Google Scholar PubMed
33. Kolli VK, Abraham P, Isaac B. Alteration in antioxidant defense mechanisms in the small intestines of methotrexate treated rat may contribute to its gastrointestinal toxicity. Cancer Ther 2007;5:501–10.Search in Google Scholar
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