Open Access Open Access  Restricted Access Subscription Access

Novel Therapeutic Intervention using Coenzyme Q10 and Insulin Sensitizer on Experimentally- Initiated Diabetic Neuropathy


Affiliations
1 Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India
2 Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa – 388421, Gujarat, India
 

Diabetes is one of the main disease having many repercussions due to which there is a huge economic burden globally. Therefore, there is a need of good therapeutic intervention by using some nutraceuticals to combat this dreadful disease especially complications such as diabetic neuropathy where patients suffer from severe pain and disability. Therefore, nutraceuticals like coenzyme Q10 and metformin were used in this study to see how they are effective in alleviating the symptoms of diabetic peripheral neuropathy. The animal experiments were conducted to induce neuropathy by using streptozotocin-nicotinamide. Animals were divided into five groups such as control, diabetic control, coenzyme Q10, metformin, and their combination. The nerve function test was conducted by using paw withdrawal response, tail-flick response, and muscular grip strength. Antioxidant parameters were assessed by estimating such MDA, SOD, and GSH. The sciatica nerve was isolated and a histopathological examination was conducted. Neuropathy was assessed in diabetic control animals which showed a substantial decrease in grip strength, increase in the paw withdrawal, and tail-flick response. It was found that there was a rapid improvement in nerve function test when a combination of coenzyme Q10 and metformin was given together as compared to animals given coenzyme Q10 and metformin alone. From this study, it is shown that combination therapy exhibited a better improvement in the nerve function test and control of the free radical generation which ultimately results in nerve damage.


Keywords

Histopathological Examination, Metformin, Nerve Damage, Nutraceutical, Streptozotocin-nicotinamide.
Font Size

User

Notifications
JOURNAL COVERS
  

  • Zangiabadi N, Asadi-Shekaari M, Sheibani V, Jafari M, Shabani M, Asadi AR, et al. Date fruit extract is a neuroprotective agent in diabetic peripheral neuropathy in streptozotocin-induced diabetic rats: A multimodal analysis. Oxid Med Cell Longev. 2011. https://doi.org/10.1155/2011/976948. PMid:22191015. PMCid:PMC3236446
  • Gallieni M, Aiello A, Tucci B, Sala V, Brahmochary Mandal SK, Doneda A, et al. The burden of hypertension and kidney disease in Northeast India: The Institute for Indian Mother and Child noncommunicable diseases project. Sci World J. 2014. https://doi.org/10.1155/2014/320869. PMid:24616621. PMCid:PMC3927758
  • Belchetz PE, Hammond PJ. Mosby’s color atlas and text of diabetes and endocrinology. Elsevier Health Sciences; 2003.
  • Houreld NN. Shedding light on a new treatment for diabetic wound healing: A review on phototherapy. Sci World J. 2014. https://doi.org/10.1155/2014/398412. PMid:24511283. PMCid:PMC3913345
  • Gilron I, Coderre TJ. Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007; 12(1);113–26. https:// doi.org/10.1517/14728214.12.1.113. PMid:17355217
  • Clark Jr CM, Lee DA. Prevention and treatment of the complications of diabetes mellitus. N Eng J Med. 1995; 332(18):1210–7. https://doi.org/10.1056/ NEJM199505043321807. PMid:7700316
  • Arner S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain. 1988; 33(1):11–23. https://doi.org/10.1016/0304- 3959(88)90198-4
  • Abuaisha BB, Costanzi JB, Boulton AJ. Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study. Diabetes Res Clin Pract. 1998; 39(2):115–21. https://doi.org/10.1016/ S0168-8227(97)00123-X
  • Apfel SC. Introduction to diabetic neuropathy. Am J Med. 1999; 107(2):1S. https://doi.org/10.1016/S0002- 9343(99)00006-6
  • Baynes JW, Thorpe R. Role of oxidative stress in diabetic complications. A new perspective on an old paradigm. Diabetes. 1999; 48:1–9. https://doi. org/10.2337/diabetes.48.1.1. PMid:9892215
  • Kandhare AD, Raygude KS, Ghosh P. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia 2012; 83:650–9. https://doi. org/10.1016/j.fitote.2012.01.010. PMid:22343014
  • Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, Döring F. Functions of coenzyme Q10 in inflammation and gene expression. Biofactors. 2008; 32(1–4):179–83. https://doi.org/10.1002/ biof.5520320121. PMid:19096114
  • Kohli Y, Suto Y, Kodama T. Effect of hypoxia on acetic acid ulcer of the stomach in rats with or without coenzyme Q10. Jpn J Exp Med. 1981; 51:105–8. PMid:7277789.
  • Lenaz G, Fato R, Formiggini G, Genova ML. The role of Coenzyme Q in mitochondrial electron transport. Mitochondrion. 2007; 7:S8–33. https://doi. org/10.1016/j.mito.2007.03.009. PMid:17485246
  • Alhaider AA, Korashy HM, Sayed-Ahmed MM, Mobark M, Kfoury H, Mansour MA. Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact. 2011; 192(3):233–42. https://doi.org/10.1016/j. cbi.2011.03.014. PMid:21457706
  • Ma J, Yu H, Liu J, Chen Y, Wang Q, Xiang L. Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin. Eur J Pharmacol. 2015; 764:599– 606. https://doi.org/10.1016/j.ejphar.2015.06.010. PMid:26054810
  • Maheshwari RA, Khatri K, Sailor GU, Balaraman R. Antidiabetic activity of Dibolin (a polyherbal formulation) in streptozotocin-nicotinamide induced type 2 diabetic rats. Int J Pharm Pharm Sci. 2014; 2:893–7.
  • Garjani A, Andalib S, Biabani S. Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat. Eur J Pharmacol. 2011; 666(1–3):135–41. https://doi. org/10.1016/j.ejphar.2011.04.061. PMid:21570962
  • Waisundara VY, Hsu A, Tan BK, Huang D. Baicalin reduces mitochondrial damage in streptozotocin‐ induced diabetic Wistar rats. Diabetes Metab Res Rev. 2009; 25(7):671–7. https://doi.org/10.1002/ dmrr.1005. PMid:19688721
  • Sharma AK, Sharma A, Kumari R, Kishore K, Sharma D, Srinivasan BP, et al. Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats. J Biomed Res. 2012; 26(3):200–10. https://doi.org/10.7555/JBR.26.20110054. PMid:23554750. PMCid:PMC3596070
  • Woolfe G, MacDonald AD. The evaluation of the analgesic action of pethidine hydrochloride (Demerol). J Pharmacol Exp Ther. 1944; 80:300–7.
  • Sharma SS, Kumar A, Kaundal R. 4-Amino 1,8-napthalimide: A potent PARP inhibitor, its neuroprotective role in experimental diabetic neuropathy. Life Sci. 2008; 82:570–6. https://doi. org/10.1016/j.lfs.2007.11.031. PMid:18262571
  • Slater TF, Sawyer BC. The stimulatory effect of carbon tetrachloride and other halogenalkane or peroxidative reaction in the rat liver functions in vitro. Biochem J. 1971; 123(5):805–15. https://doi.org/10.1042/ bj1230805. PMid:4399399. PMCid:PMC1177080
  • Mishra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay of superoxide dismutase. J Biol Chem. 1972; 247(10):3170–5. https://doi.org/10.1016/S0021- 9258(19)45228-9
  • Moron MS, Depierre JW. Levels of glutathione, glutathione reductase and glutathione S transferase activities in rat lung and liver. Biochim Biophys Acta. 1999; 582(1):67–78. https://doi.org/10.1016/0304- 4165(79)90289-7
  • Maheshwari R, Pandya B, Balaraman R, Seth AK, Yadav YC, Sankar VS. Hepatoprotective effect of Livplus-A polyherbal formulation. Pharmacogn J.
  • ; 7(5):311–6. https://doi.org/10.5530/pj.2015.5.11
  • Kumar A, Kaundal RK, Iyer S, Sharma SS. Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. Life Sci. 2007; 80(13):1236–44. https:// doi.org/10.1016/j.lfs.2006.12.036. PMid:17289084
  • Stevens MJ, Obrosova I, Cao X, Van Huysen C, Greene DA. Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes. 2000; 49(6):1006–15. https:// doi.org/10.2337/diabetes.49.6.1006. PMid:10866054
  • Sayyed SG, Kumar A, Sharma SS. Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in experimental diabetic neuropathy. Life Sci. 2006; 79:777–83. https://doi.org/10.1016/j.lfs.2006.02.033. PMid:16581090
  • Cui XP, Li BY, Gao HQ, Wei N, Wang WL, Lu M. Effects of grape seed proanthocyanidin extracts on peripheral nerves in streptozocin-induced diabetic rats. Nutr Sci Vitaminol. 2008; 54(4):321–8. https:// doi.org/10.3177/jnsv.54.321. PMid:18797155
  • Arora M, Kumar A, Kaundal RK, Sharma SS. Amelioration of neurological and biochemical deficits by peroxynitrite decomposition catalysts in experimental diabetic neuropathy. Eur J Pharmacol. 2008; 596(1–3):77–83. https://doi.org/10.1016/j. ejphar.2008.08.003. PMid:18768138
  • Saini AK, Kumar HAS, Sharma SS. Preventive and curative effect of edaravone on nerve functions and oxidative stress in experimental diabetic neuropathy. Eur J Pharmacol. 2007; 568:164–72. https://doi. org/10.1016/j.ejphar.2007.04.016. PMid:17521626

Abstract Views: 148

PDF Views: 87




  • Novel Therapeutic Intervention using Coenzyme Q10 and Insulin Sensitizer on Experimentally- Initiated Diabetic Neuropathy

Abstract Views: 148  |  PDF Views: 87

Authors

Rajesh A. Maheshwari
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India
Ramachandran Balaraman
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India
Ashim Kumar Sen
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India
Umang Shah
Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa – 388421, Gujarat, India
Kinjal P. Patel
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India
Dhanya B. Sen
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India

Abstract


Diabetes is one of the main disease having many repercussions due to which there is a huge economic burden globally. Therefore, there is a need of good therapeutic intervention by using some nutraceuticals to combat this dreadful disease especially complications such as diabetic neuropathy where patients suffer from severe pain and disability. Therefore, nutraceuticals like coenzyme Q10 and metformin were used in this study to see how they are effective in alleviating the symptoms of diabetic peripheral neuropathy. The animal experiments were conducted to induce neuropathy by using streptozotocin-nicotinamide. Animals were divided into five groups such as control, diabetic control, coenzyme Q10, metformin, and their combination. The nerve function test was conducted by using paw withdrawal response, tail-flick response, and muscular grip strength. Antioxidant parameters were assessed by estimating such MDA, SOD, and GSH. The sciatica nerve was isolated and a histopathological examination was conducted. Neuropathy was assessed in diabetic control animals which showed a substantial decrease in grip strength, increase in the paw withdrawal, and tail-flick response. It was found that there was a rapid improvement in nerve function test when a combination of coenzyme Q10 and metformin was given together as compared to animals given coenzyme Q10 and metformin alone. From this study, it is shown that combination therapy exhibited a better improvement in the nerve function test and control of the free radical generation which ultimately results in nerve damage.


Keywords


Histopathological Examination, Metformin, Nerve Damage, Nutraceutical, Streptozotocin-nicotinamide.

References





DOI: https://doi.org/10.18311/jnr%2F2022%2F30085