Short Communication Annals of Pharmacology and Pharmaceutics Published: 20 Aug, 2017
An Insight into Antioxidant Therapeutics
Bairy LK1*, Ommurugan B2 and Amita D2 1Department of Pharmacology, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE
2Department of Pharmacology, Kasturba Medical College, Manipal University, India
Abstract Free radicals and oxidants have beneficial and harmful effects on the body. They are generated either during normal cell metabolism or from external agents such as drugs, radiation, nicotine smoke, pollution. Over production of these leads to accumulation in the body resulting oxidative stress. Oxidative stress may result in the development of chronic and degenerative diseases like neoplasm, autoimmune disorders, premature aging, cataract, infertility, metabolic syndrome, cardiovascular diseases and neurodegenerative disorders. The human body has inbuilt mechanism to deal with oxidative stress to a certain extent. However, we may have to use antioxidants whenever there is imbalance between the productions and counteract mechanisms. This short communication focuses on the use of antioxidants in the treatment of gastric mucosal disorders, male infertility and on statin induced new onset Diabetes mellitus and myopathy.
Introduction Oxidative stress is defined as disturbance in physiological hemostasis of the biological system due to imbalance between reactive oxygen species and ability of the human body to clear it. Reactive oxygen species are continuously produced in human body due to cellular metabolism, physical and psychological stress, various drugs, environmental toxins, and ultraviolet exposure [1]. Reactive oxygen species plays an important role in cell signaling, regulation of growth factor, immunomodulation, and cellular apoptosis [1]. Oxidative stress is implicated in pathogenesis of various diseases which includes liver injury, neurodegenerative diseases, inflammatory joint diseases, Diabetes mellitus, infertility, ageing, cataract, shock related cell injury, myopathy, atherosclerosis, essential hypertension as well as other disorders [2]. This mini review focuses on the use of antioxidants in the treatment of gastric mucosal disorders, male infertility and on statin induced new onset diabetes mellitus and myopathy. Role of Antioxidants in Male Factor Infertility OPEN ACCESS Infertility affects 8% to 12% of couples worldwide with regional variations, male factor *Correspondence: infertility being an important cause in about 50% of cases [3,4]. Spermatogenesis, involves increased Bairy LK, Department of Pahramcology, mitochondrial oxygen consumption by the germinal epithelium of testis. Increased lipid per Rak Medical and Health Sciences oxidation in the testis contributes to the suggested vulnerability of this organ to oxidative stress. University, Ras Al Khaimah, UAE, The attributable causes include exposure to toxins, smoking, alcohol, obesity, radiation, drugs, E-mail: [email protected] urogenital abnormalities, and inflammatory conditions affecting the male reproductive tract. So to Received Date: 02 May 2017 protect this testis has antioxidant defence system characterized by various enzymes like NADPH reductase, gluthatione peroxidase, superoxide dismutase, catalase. Apart from these enzymes there Accepted Date: 13 Jul 2017 are various small molecule factors protecting the testis from oxidative damage including zinc, Published Date: 20 Aug 2017 vitamin C, vitamin E, melatonin [5]. There are many drugs implicated in causing male infertility Citation: which includes antineoplastic drugs like cyclophosphamide, busalfan, cisplatin, melphalan, Bairy LK, Ommurugan B, Amita D. An chlorambucil. Other class of drugs known to cause infertility includes corticosteroids, estrogens, Insight into Antioxidant Therapeutics. neuroleptic agents, spironolactone, cimetidine, and even thyroid supplements [6]. All these factors Ann Pharmacol Pharm. 2017; 2(8): cause infertility in males by causing oxidative damage to testicular membrane thereby leading 1081. alteration in sperm counts, structural and DNA damage to sperms and by causing disorganization Copyright © 2017 Bairy LK. This is an of seminiferous tubules of testis [7]. Our research mainly focuses on use of Coenzyme Q 10, L- open access article distributed under Glutamine, Atorvastatin, Melatonin as antioxidants in the treatment of reversal of fertility changes the Creative Commons Attribution caused by anticancer drugs, nicotine exposure and physical stress induced infertility. As per License, which permits unrestricted literature evidence there are few studies have been carried out using Coenzyme Q 10, L-glutamine, use, distribution, and reproduction in melatonin, and Atorvastatin as antioxidants. It was proved that exogenous administration any medium, provided the original work of Coenzyme Q 10 helped improving sperm parameters in idiopathic asthenozoopermia [8]. Glutamine, an abundant amino acid in human body, besides its role as a constituent of proteins and is properly cited.
Remedy Publications LLC. 1 2017 | Volume 2 | Issue 8 | Article 1081 Bairy LK, et al., Annals of Pharmacology and Pharmaceutics its importance as metabolic fuel, has nonnutritive effects, including be done using L-Glutamine and Coenzyme Q 10 in reversing as well regulation of the cellular redox balance, cell volume, glutathione preventing statin induced myopathy. So, our area of research mainly metabolism, and attenuation of oxidative stress [9]. Several studies focuses on using these antioxidants in targeting both myopathy as have shown that glutamine administration attenuates oxidative stress well as glycemic changes induced by statins by supplementing these and protects against chemotherapeutic agent induced organ injury drugs along with the statins during treatment and to find out whether [9]. Hence coenzyme Q 10 and L-glutamine can be potentially used physical exercise as a part of treatment regimen during statins in reversing the fertility changes caused by anticancer drugs and our ameliorates or attenuates myopathy when implemented along with area of research focuses on use of Coenzyme Q 10 and L- Glutamine antioxidant treatment. in reversing methotrexate induced testicular damage. Role of Antioxidants in the Peptic Ulcer Recently it was found out that Nitric oxide has been implicated Disease as the major free radical in nicotine induced oxidative stress injury Helicobacter pylori, non-steroidal anti-inflammatory drugs to testicular tissue leading to irreversible infertility [10]. Melatonin, (NSAIDS), emotional stress, alcohol abuse, and smoking are the a natural antioxidant found in human body is also one among principal etiological factors associated with peptic ulcer [22]. The well-known hormone inhibiting nitric oxide levels [11]. So, our exact mechanisms have been studied upon since years, some of them research also throws light on the use of melatonin in the treatment being impairment in the gastric mucosal anti-oxidant mechanism, of nicotine induced testicular damage and on treatment of anticancer production of free radicals and local irritation of the mucosa [22]. drug induced testicular damage. The major idea behind using these Gastroduodenal ulcers, GI malignancies, and inflammatory bowel antioxidants in reversing the testicular damage caused by anticancer disease (IBD) arise in part from oxidative stress. There are various drugs is purely due to its protective role in testis as well also in studies suggesting that oxidative stress is one of the major factors maintaining the positive nitrogen balance in cancer patients and in in the pathogenesis of peptic ulcer disease. There are few studies preventing injury to other organs due to anticancer drug induced which proved the effectiveness of coenzyme Q 10 in preventing oxidative stress. Use of Atorvastatin in hyperlipidemia induced male analgesic induced peptic ulcer [23]. Recent evidence has implicated infertility is well known but there was one pilot study done which stress induced gastric ulcers are mainly due to free radical damage said Atorvastatin has detrimental effects in sperm parameters and to the gastric epithelium. So, our research focuses mainly on using cause infertility [12]. But the use of Atorvastatin as antioxidant in Coenzyme Q 10 and L-glutamine in the treatment of peptic ulcer atherosclerosis has been proven recently and hence forth the use of disease due to stress and ethanol as both share the common pathway of Atorvastatin as a potential antioxidant in treatment of stress related free radical induced gastric damage. Also, various plant products have male infertility is one such focus of interest in our research [13]. been identified which have anti-inflammatory as well as antioxidant Role of Antioxidants Statin Induced New property. The sesame oil lignan sesamol (3,4-methylenedioxyphenol) Onset Diabetes mellitus is said to have potent antioxidative properties [24]. Bisphosphonates are known to cause gastric irritation and peptic ulcers. The mechanism In February 2012, Food and Drug Administration released of bisphosphonate induced gastric injury is mainly via generation of the information that Statins increase hemoglobin (HbA1C) and free radicals [25]. So, the aim of our research is to study the effect of fasting serum glucose levels. Statin therapy was associated with sesame seed extract on bisphosphonate induced gastric ulcers and to 9% increased risk of incident diabetes in a recent meta analysis find out the role of sesame seeds as effective drugs in management of involving randomized controlled trials [14]. Over-production of peptic ulcer disease via their antioxidant mechanism. NO, suppression of insulin secretion by oxidative stress has been found to be the major cause in hyperglycemia associated with statins. Conclusion Oxidative stress by Atorvastatin has been found to inhibit adipocyte The role of antioxidants in treatment of various diseases like peptic differentiation and hence impair insulin sensitivity [15]. Reported ulcer, male infertility, statin induced new onset Diabetes mellitus various effects of coenzyme Q10 treatment in streptozotocin- and myopathy is an emerging trend in the medical field. So, future induced diabetic rats [16]. Literature evidence says supplementing research must be done using these novel antioxidant molecules like a high-fat diet with Glutamine attenuated hyperglycemia in a coenzyme Q 10, L-glutamine, Melatonin to find appropriate dosages diabetic rodent model [17]. So further research can be implicated and also to find out correct treatment protocols to use these agents. in using Coenzyme Q 10 as well L-glutamine in the treatment and From pharmaceutical point of view different formulations of these prevention of Statin induced glycemic changes and hence it has agents can be tried for treatment of various diseases. Further clinical been the focus of interest of our research agenda. Although statins trials can be undertaken to add to the current evidence database for are well tolerated by most people, the association of their use with practicing safe medicine with these agents. a low incidence of myopathy is well established, however, the risk of rhabdomyolysis with the currently marketed statins is very low References [18,19]. Statin-induced myopathy is a heterogeneous condition with 1. Gupta RK, Patel AK, Shah N, Chaudhary AK, Jha UK, Yadav UC. multiple pathophysiologic causes. It may be due to the mechanism Oxidative stress and antioxidants in disease and cancer: Asian Pac J Cancer of action of the drug per se, interactions with other drugs, or genetic, Prev. 2014;15(11):4405-9. metabolic, immunological vulnerabilities. Muscle metabolism is 2. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease adversely impacted by statin therapy through various mechanisms. and health. Int J Biomed Sci. 2008;4(2):89-96. The lack of CoQ10 has been postulated to be an etiologic factor for statin-associated myopathy [20]. Also, literature says possible role 3. Sciarra J. Infertility an international health problem. Int J Gynaecol Obstet. for Glutamine in stimulating anabolic processes, including muscle 1994;46(2):155-63. glycogen and protein synthesis [21]. Hence future research could 4. Paul C Adamson, Karl Krupp, Alexandra H, Jeffrey D, Klausner, Arthur
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L. Purnima Population Council. New Delhi: Population Council; 15. Nakata M, Uto N, Maruyama I, Yada T. Nitric oxide induces apoptosis via 2004. Infertility. Looking Back, Looking Forward: A Sex Heal Ind. Ca2+-dependent processes in the pancreatic beta-cell line MIN6. Cell Struct 2011;134(4):440-446. Funct.1999;24:451-5. 5. Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the 16. Singh RB, Niaz MA, Rastogi SS. Effect of hydrosoluble coenzyme Q10 testes. Oxid Med Cell Longev. 2008;1(1):15-24. on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens. 1999;13:203-8. 6. Meistrich ML. Male Gonadal Toxicity. Pediatric blood & cancer. 2009;53(2):261-266. 17. Groener JE, van Gent T, van Tol A. Effect of lipid transfer protein on plasma lipids, apolipoproteins and metabolism of high-density lipoprotein 7. Esin Yuluğ, Sibel Türedi, Ahmet Alver, Süleyman Türedi, Cemil cholesteryl ester in the rat. Biochim Biophys Acta.1989;1002:93-100. Kahraman. Effects of Resveratrol on Methotrexate-Induced Testicular Damage in Rats. The Scientific World Journal, 2013. 18. Rosenson RS. Current overview of statin-induced myopathy. Am J Med. 2004;116:408-16. 8. Lafuente R, González-Comadrán M, Solà I, López G, Brassesco M, Carreras R, et al. Coenzyme Q10 and male infertility: a meta-analysis. J 19. Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, et Assist Reprod Genet. 2013;30(9):1147-56. al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid- lowering drugs. JAMA. 2004;292:2585-90. 9. Heyland DK, Dhaliwal R, Day AG, Muscedere J, Drover J, Suchner U, et al. Reducing Deaths due to Oxidative Stress (The REDOXS Study): rationale 20. Kalra S. The role of Coenzyme Q10 in statin-associated myopathy. J Am and study design for a randomized trial of glutamine and antioxidant Coll Cardiol. 2009;1:2-8. supplementation in critically-ill patients. Proc Nutr Soc.2000;65:250-263. 21. Gleeson M. Dosing and efficacy of glutamine supplementation in human 10. O'Bryan MK, Schlatt S, Gerdprasert O, Phillips DJ, de Kretser DM, exercise and sport training. The J nutr. 2008;138(10):2045S-9S. Hedger MP. Inducible Nitric Oxide Synthase in the Rat Testis: Evidence 22. Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. The Lancet. for Potential Roles in Both Normal Function and Inflammation-Mediated 2009;374(9699):1449-61. Infertility. Biol Reprod. 2000;63(5):1285-93. 23. El-Abhar HS. Coenzyme Q10: A novel gastroprotective effect via 11. Aydogan S, Yerer MB, Goktas A. Melatonin and nitric oxide. J Endocrinol modulation of vascular permeability, prostaglandin E 2, nitric oxide Invest. 2006;29(3):281-7. and redox status in indomethacin-induced gastric ulcer model. Eur J 12. Pons-Rejraji H, Brugnon F, Sion B. Evaluation of atorvastatin efficacy Pharmacol. 2010;649(1):314-9. and toxicity on spermatozoa, accessory glands and gonadal hormones of 24. Hsu DZ, Chen KT, Li YH, Chuang YC, Liu MY. Sesamol delays mortality healthy men: a pilot prospective clinical trial. Reproductive Biology and and attenuates hepatic injury after cecal ligation and puncture in rats: role Endocrinology: RB&E. 2014;12:65. of oxidative stress. Shock. 2006;25(5):528-32. 13. Shishehbor MH, Brennan ML, Aviles RJ, Fu X, Penn MS, Sprecher DL, 25. Silva RO, Lucetti LT, Wong DV, Aragão KS, Junior EM, Soares PM, et et al. Statins promote potent systemic antioxidant effects through specific al. Alendronate induces gastric damage by reducing nitric oxide synthase inflammatory pathways. Circulation. 2003;108(4):426-31. expression and NO/cGMP/KATP signaling pathway. Nitric oxide. 14. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et 2014;40:22-30. al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.
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