PENGARUH MADU TRIGONA TERHADAP STRESS OKSIDATIF PADA TIKUS PUTIH (Rattus norvegicus) YANG DIINDUKSI STATIN UNTUK MENCEGAH MIOTOKSISITAS

Authors

  • Mirnawati Salampe Biomedik Farmakologi, Pascasarjana Universitas Hasanuddin, Makassar
  • Peter Kabo 2Bagian Farmakologi, Fakultas Kedokteran, Universitas Hasanuddin
  • Yulia Yusrini Djabir Fakultas Farmasi, Universitas Hasanuddin, Makassar

Abstract

Tujuan penelitian ini adalah mengetahui pengaruh madu trigona terhadap stress oksidatif pada tikus putih yang diinduksi statin untuk mencegah miotoksisitas melalui pengukuran kadar kreatin kinase (CK), malondialdehid (MDA), dan aktivitas superoksida dismutase (SOD). Penelitian ini menggunakan 30 ekor tikus jantan yang dibagi menjadi 6 kelompok, terdiri dari 5 ekor tiap kelompok. Kelompok 1 merupakan kontrol yang hanya diberikan NaCMC 0,5%; kelompok 2 (induksi atorvastatin 20 mg/kgBB selama 3 minggu dan dilanjut dengan 40 mg/kgBB selama 2 minggu); kelompok 3 (diberi madu 4,5 ml/kgBB); kelompok 4, 5, dan 6 (diberi madu 1,5 ml; 3 ml; 4,5 ml/kgBB, berturut-turut selanjutnya selang waktu 2 jam diinduksi atorvastatin). Hasil penelitian menunjukkan bahwa kadar CK sebelum dan setelah perlakuan selama lima minggu pada tikus yang diinduksi atorvastatin mengalami peningkatan secara signifikan (p<0.05), sedangkan kadar CK pada kelompok tikus yang lainnya tidak menunjukkan perubahan yang bermakna. Kadar MDA setelah perlakuan pada tikus yang hanya diinduksi atorvastatin menunjukkan kadar yang relatif tinggi, namun secara statistik tidak menunjukkan perbedaan bermakna dengan kelompok tikus yang lainnya.  Demikian pula dengan aktivitas SOD pada tikus yang hanya diinduksi atorvastatin tidak menunjukkan perbedaan bermakna dengan kelompok tikus yang diberi madu sebelum induksi atorvastatin.

References

Istvan ES, Deisenhofer J. Structural Mechanism for Statin Inhibition of HMG-CoA Reductase Structural Inhibition Mechanism of for Statin Reductase. Adv Sci. 2009;292(5519):1160–4.

Bełtowski J. Statins and modulation of oxidative stress. Toxicol Mech Methods. 2005;15(2):61–92.

Baer AN, Wortmann RL. Myotoxicity associated with lipid-lowering drugs. Curr Opin Rheumatol. 2007;19(1):67–73.

Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy - European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36(17):1012–22.

Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, Grenade L La, et al. Incidence of Hospitalized Rhabdomyolysis in Patients with Lipid lowering Drugs. 2004;292(21):6.

Tomaszewski M, Stêpieñ KM, Tomaszewska J, Czuczwar SJ. Statin-induced myopathies. 2011;859–66.

Kaufmann P, Török M, Zahno A, Waldhauser KM, Brecht K, Krähenbühl S. Toxicity of statins on rat skeletal muscle mitochondria. Cell Mol Life Sci. 2006;63(19–20):2415–25.

Marcoff L, Thompson PD. The Role of Coenzyme Q10 in Statin-Associated Myopathy. A Systematic Review. J Am Coll Cardiol. 2007;49(23):2231–7.

Apostolopoulou M, Corsini A, Roden M. The role of mitochondria in statin-induced myopathy. Eur J Clin Invest. 2015;45(7):745–54.

Hattori Y, Nakanishi N, Kasai K. Tra Ct. Cardiovasc Res. 2002;54:649–58.

Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxidative stress and toxicity. J Toxicol. 2012;2012.

Busanello ENB, Marques AC, Lander N, de Oliveira DN, Catharino RR, Oliveira HCF, et al. Pravastatin chronic treatment sensitizes hypercholesterolemic mice muscle to mitochondrial permeability transition: Protection by creatine or coenzyme Q10. Front Pharmacol. 2017;8(APR):1–11.

Bouitbir J, Charles AL, Echaniz-Laguna A, Kindo M, Daussin F, Auwerx J, et al. Opposite effects of statins on mitochondria of cardiac and skeletal muscles: A “mitohormesis” mechanism involving reactive oxygen species and PGC-1. Eur Heart J. 2012;33(11):1397–407.

Soner BC, Inan SY, Guven U, Oktem G, Sahin AS. Combined treatment with resveratrol prevents the atorvastatin-induced myopathy in rat skeletal muscle. African J Pharm Pharmacol. 2013;7(18):1114–8.

Deichmann R, Lavie C, Andrews S. Coenzyme q10 and statin-induced mitochondrial dysfunction. Ochsner J. 2010;10(1):16–21.

Krishnasree V, Ukkuru PM. Phytochemical screening and antioxidant activity of diff erent bee honeys. J Med Herbs Ethnomedicine. 2015;1(1):38–44.

Uttara B, Singh A V, Zamboni P, Mahajan RT. Oxidative Stress and Neurodegenerative Diseases : A Review of Upstream and Downstream Antioxidant Therapeutic Options. Curr Neuropharmacol. 2009;7(1):65–74.

Rao PV, Krishnan KT, Salleh N, Gan SH. Biological and therapeutic effects of honey produced by honey bees and stingless bees: A comparative review. Brazilian J Pharmacogn. 2016;26(5):657–64.

Beltowski J, Wójcicka G, Jamroz-Wisniewska A. Adverse Effects of Statins - Mechanisms and Consequences. Curr Drug Saf. 2009;4:209–28.

Elshama SS, El-Kenawy AE-M, Osman H-EH. Curcumin improves atorvastatin-induced myotoxicity in rats: Histopathological and biochemical evidence. Int J Immunopathol Pharmacol. 2016;29(4):742–52.

Rodrigues AC. Efflux and uptake transporters as determinants of statin response. Expert Opin Drug Metab Toxicol. 2010;6(5):621–32.

Knauer MJ. The Role of Drug Transporters in Statin-Induced Myopathy. 2012;(December).

Urbano F, Bugliani M, Filippello A, Scamporrino A, Mauro D, Pino A Di, et al. Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β -Cells . Direct Effect of Oxidative Stress. Sci Rep. 2017;(August):1–17.

Al-Waili NS. Effects of Daily Consumption of Honey Solution on Hematological Indices and Blood Levels of Minerals and Enzymes in Normal Individuals. J Med Food. 2003;6(2):135–40.

Tartibian B, Mostafapour M, Esmailpour HM. The Effect of Honey Supplement on the Inflammation Factors of Plasma of the Handbalist Young Men. Int J Sport Stud. 2015;5(1):38–41.

Fukai T, Ushio-Fukai M. Superoxide Dismutases: Role in Redox Signaling, Vascular Function, and Diseases. Antioxid Redox Signal. 2011;15(6):1583–606.

Esterbauer H, Eckl P, Ortner A. Possible mutagens derived from lipids and lipid precursors. Mutat Res Genet Toxicol. 1990;238(3):223–33.

Panonnummal R, Varkey J. Statins induced nephrotoxicity: A dose dependent study in albino rats. Int J Pharm Pharm Sci. 2014;6(11):401–6.

Shu N, Hu M, Ling Z, Liu P, Wang F, Xu P, et al. The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1. Sci Rep.

;6(September):33072.

Galal RM, Zaki HF, Seif El-Nasr MM, Agha AM. Potential protective effect of honey against paracetamol-induced hepatotoxicity. Arch Iran Med. 2012;15(11):674–80.

Abdul Sani NF, Belani LK, Pui Sin C, Abdul Rahman SNA, Das S, Zar Chi T, et al. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic sprague-dawley rats. Biomed Res Int. 2014;2014(May).

Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative Stress and Antioxidant Defense. World Allergy Organ J. 2012;(January):9–19.

Azadmanesh J, Borgstahl G. A Review of the Catalytic Mechanism of Human Manganese Superoxide Dismutase. Antioxidants. 2018;7(2):25.

Mohammadi M, Amini R, Jahanbakhsh Z, Shekarforoush S. Effects of atorvastatin on the hypertension-induced oxidative stress in the rat brain. Iran Biomed J. 2013;17(3):152–7.

Larsen S, Ci MS, Stride N, Hey-mogensen M, Hansen CN, Bang LE, et al. Simvastatin Effects on Skeletal Muscle Relation to Decreased Mitochondrial Function and Glucose Intolerance. JAC. 2013;61(1):44–53.

Okuyama H, Langsjoen PH, Hamazaki T, Ogushi Y, Hama R, Kobayashi T, et al. Statins stimulate atherosclerosis and heart failure : pharmacological mechanisms Statins stimulate atherosclerosis and heart failure : pharmacological mechanisms. Expert Rev Clin Pharmacol. 2015;8(2):189–99.

Banjarnahor SDS, Artanti N. Antioxidant properties of flavonoids. Med J Indones. 2014;23(4):239–44.

Downloads

Published

2018-12-19

Issue

Section

Articles