Effects of L-Carnitine and Co-enzyme Q10 Together with ACE Inhibitors on Total Oxidant and Antioxidant Levels in L-Name Hypertensive Rats

Yıl 2017, Cilt: 12 Sayı: 2, 143 - 151, 30.10.2017

Nadide Nabil Kamiloğlu

https://doi.org/10.17094/ataunivbd.347966

Öz

In this study we aimed to find
out the affects of giving ACE inhibitor with L-carnitine and Co-enzyme Q₁₀
on the oxidant-antioxidant system. For this purpose, 8 week-old and
approximately 200-250 gr, 60 adult Sprague-Dawley rats were used. The animal were divided into three groups, served as 1 control and 2
experimental groups and each had 20 rats. Before starting the study, 75 mg/kg
L-NAME given intraperitonelly to all groups for ten days to create
hypertension. 10 mg/kg ACE inhibitor to the control group, 100 mg/kg L-carnitine+10
mg/kg ACE inhibitor to the L-carnitine group, 100 mg/kg Co-enzyme Q₁₀+10
mg/kg ACE inhibitor to the Co-enzyme Q₁₀ group was given. There were
statistically significant decrease in the plasma levels of total oxidant in
Co-enzyme Q10 and L-carnitine groups when compared to the control on 28^th
day (P<0.05). There were no statistically significant difference between the
groups in terms of plasma total antioxidant levels. Total oxidant levels of
heart tissue in the L-carnitine group was statistically lower than the control
group (P<0.001) on the day 14^th. There were no statistically
significant difference on the total oxidant levels of heart tissue in Co-enzyme
Q₁₀ group.The total oxidant levels of heart tissue of the experimental groups were statistically
lower than the control group on 28^th day, and this decrease was more prominent in the L-carnitine group (P
<0.001).  There were no statistically
significant difference in total antioxidant levels of heart tissue. It was
concluded that due to the antioxidant properties of L-carnitine and Co-enzyme
Q10 in hypertension, these substances protects the heart and vascular system
against free-radical damage, and also reducing the severity of secondary
problems.

Anahtar Kelimeler

ACE inhibitor, Antioxidant, Co-enzyme Q10, Hypertension, L-carnitine, Oxidant

L-Name Hipertansif Ratlarda Ace İnhibitörü ile Birlikte L-Karnitin ve Co-enzim Q10 Verilmesinin Total Oksidan ve Antioksidan Düzeyleri Üzerine Etkileri

Öz

Bu
çalışma ile L-NAME hipertansif ratlarda ACE inhibitörü ile birlikte L- karnitin
ve Co-enzim Q₁₀ verilmesinin total oksidan-antioksidan sistem
üzerine etkilerinin araştırılması amaçlandı. Bu amaçla, ortalama 200-250 gr, 8
haftalık, 60 erişkin Spraque-Dawley rat kullanıldı. Ratlar her grupta 20 rat
bulunacak şekilde, 1 kontrol ve 2 deney grubu olmak üzere 3 gruba ayrıldı.
Çalışmaya başlamadan önce tüm gruplara 10 gün süreyle intraperitonel (i.p)
olarak 75 mg/kg L- NAME verilerek hipertansiyon oluşturuldu. Hipertansiyon
oluşturulduktan sonra, Kontrol grubuna 10 mg/kg ACE inhibitörü, L-karnitin
grubuna 10 mg/kg ACE inhibitörü + 100 mg/kg L-karnitin, Co-enzim Q₁₀
grubuna 10 mg/kg ACE inhibitörü + 100 mg/kg Co-enzim Q₁₀ ip olarak
verildi. Plazma total oksidan düzeylerinin hem L-karnitin hem de Co-enzim Q₁₀
gruplarında, kontrol grubuna göre 28. günde istatistiksel olarak önemli düzeyde
düşük olduğu belirlendi (P<0.05). Plazma total antioksidan düzeylerinde
gruplar arasında istatistiksel olarak bir farklılık gözlenmedi. Kalp dokusu
total oksidan düzeylerinin 14. günde L-karnitin grubunun kontrol grubuna göre
istatistiksel olarak daha düşük olduğu (P<0.001), Co-enzim Q₁₀
grubunda ise istatistiksel olarak önemli bir fark olmadığı belirlendi. 28.
günde deneme gruplarının kalp dokusu total oksidan düzeylerinin kontrol grubuna
göre istatistiksel olarak düşük olduğu, bu düşüşün L-karnitin uygulanan grupta
daha belirgin olduğu görüldü (P<0.001). Kalp dokusu total antioksidan
düzeylerinde istatistiksel olarak bir farklılık tespit edilmedi. Sonuç olarak,
L-karnitin ve Co-enzim Q₁₀’nun hipertansiyonda kalbi ve damar
sistemini serbest radikal hasarından koruyarak, oluşacak ikincil problemlerin
şiddetini azaltabilecekleri kanaatine varıldı.

Anahtar Kelimeler

ACE inhibitörü, Antioksidan, Co-enzim Q10, Hipertansiyon, L-karnitin, Oksidan

Kaynakça

• 1. Cohuet G., Struijker-Bouder H., 2006. Mechanism of target organ damage caused by hypertension:Therapeutic potential. Pharm Therap, 111, 81-98.
• 2. Yılmaz G., Aksulu HE., Demirel E., Ercan ZS., Zengil H., Türker RK., 1987. Modulation by endothelium of the vascular effects of angiotensin II. Agents Actions, 21, 184-190. 3. Rochette L., Lorin J., Zeller M., Guilland JC., Lorgis L., Cottin Y., Vergely C., 2013. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets?. Pharm Therap, 140, 239-257.
• 4. Landmesser U., Dikalov S., Price SR., McCann L., Fukai T., Holland SM., Mitch WE., Harrison DG., 2003. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest, 111, 1201-1209. 5. Magy L., Vincent F., Faure S., Messerli FH., Wang JG., Achard JM., Fournier A., 2005. The renin-angiotensin systems: evolving pharmacological perspectives for cerebroprotection. Curr Pharm Des, 11, 3275-3291.
• 6. Arı UÇ., Kamiloğlu NN., 2015. Erkek sığırlarda ürogenital sistem anatomisi ve fizyolojisi. Türk Klin J Vet Sci-Surg- Special Topics, 1, 1-11.
• 7. Kurusaki R., Muramatsu Y., Kato H., Watanabe Y., Imai Y., Itoyama Y., Araki T., 2005. Effect of angiotensin-coverting enzyme inhibitor perindopril on interneurons in MPTP-treated mice. Europan Neuropsychopharmacology, 15, 57-67.
• 8. Lopez-Real A., Rey P., Soto-Otero R., Mendez- Alvarez E., Labandeira-Garcia JL., 2005. Angiotensin-converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6 hydroxydopamine rat model of Parkinsonism. J Neurosci Res, 81, 865-873.
• 9. Wright JT., Bakris G., Grene T., Agodoa LY., Apel LJ., Charleston J., Cheek D., Douglas-Baltimore JG., Gassman J., Glassock R., Hebert L., Jamerson K., Lewis J., Phillips RA., Toto RD., Middleton JP., Rostand SG., 2002. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. J Am Med Assoc, 288, 2421-2431.
• 10. Taşar N., Şehirli Ö., Yiğiner Ö., Süleymanoğlu S., Yüksel M., Yeğen B., Şener G., 2012. Protective effects of Nigella sativa against hypertension-induced oxidative stress and cardiovascular dysfunction in rats. Marmara Pharmaceu J, 16, 141-149.
• 11. Hopkins RZ., 2016. Reactive Oxygen Species. Cell Med Press, 2, 290-297.
• 12. Halliwell B., Gutteridge JMC., 2015. Free radicals in biology and medicine, 15. Baskı, Oxford University Press, pp. 639-695.
• 13. Deng K., Wong CW., Nolan JV., 2006. Long-term effects of earlylife dietary L-carnitine on lymphoid organs and immune responses in Leghorn-type chickens. J Anim Physiol Anim Nutr, 90, 81-86.
• 14. Karadeniz A., Şimsek N., Çakir S., 2008. Haematological effects of dietary L-carnitine supplementation in broiler chickens. Revue Med Vet, 8, 437-443.
• 15. Jogl G., Hsiao YS., Tong L., 2004. Structure and function of carnitine acyltransferases. Ann NY Acad Sci, 1033, 17-29.
• 16. Ribas GS., Biancini GB., Mescka C., Wayhs CY., Sitta A., Wajner M., Vargas CR., 2012. Oxidative stress parameters in urine from patients with disorders of propionate metabolism: A beneficial effect of L-carnitine supplementation. Cell Mol Neurobiol, 32, 77-82.
• 17. Ribas GS., Vargas CR., Wajner M., 2014. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene, 533, 469-476.
• 18. Calo LA., Pagnina E., Davisb PA., Semplicinia A., Nicolaic R., Calvanic M., Pessinaa AC., 2006. Antioxidant effect of L-carnitine and its short chain esters relevance for the protection from oxidative stress related cardiovascular damage. Int J Cardiol, 107, 54-60.
• 19. Gülçin İ., 2006. Antioxidant and antiradical activities of L-carnitine. Life Sci, 78, 803-811.
• 20. Kubo H., Fujii K., Kawabe T., Matsumoto S., Kishida H., Hosoe K., 2008. Food content of ubiquinol-10 and ubiquinone-10 in the Japanese diet. J Food Compos Anal, 21, 199-210.
• 21. Parkhideh D., 2008. Methods and compositions that enhance bioavailability of coenzyme-Q10, United States Patent No: 7, 438, 903, Oct. 21.
• 22. Gürkan AS., Bozdağ-Dündar O., 2005. Coenzyme Q10. J Fac Pharm, 34, 129-154.
• 23. Loster H., Bohm U., 2001. L-carnitine reduces malondialdehyde concentrations in isolated rat hearts in dependence on perfusion conditions. Mol Cell Biochem, 217, 83-90.
• 24. Şener G., Paskaloğlu K., Satiroglu H., Alican I., Kaçmaz A., Sakarcan A., 2004. L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardiovasc Pharmacol, 43, 698-705.
• 25. Ercan P., El SN., 2010. Koenzim Q10’un beslenme ve sağlık açısından önemi ve biyoyararlılığı. TÜBAV Bil Derg, 3, 192-200.
• 26. Doggrell SA., Brown L., 1998. Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res, 39, 89-105.
• 27. Cachofeiro V., Sakakibara T., Nasjletti A., 1992. Kinins, nitric oxide, and the hypotensive effect of captopril and ramiprilat in hypertension. Hypertension, 19, 138-145.
• 28. Winter BK., Fiskum G., Gallo LL., 1995. Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. Br J Cancer, 72, 1173-1179.
• 29. Ankola DD., Viswanad B., Bhardwaj V., Ramarao P., Kumar MR., 2007. Development of potent oral nanoparticulate formulation of coenzyme Q10 for treatment of hypertension: can the simple nutritional supplements be used as first line therapeutic agents for prophylaxis/therapy?. Eur J Pharm Biopharm, 67, 361-369.
• 30. Erel O., 2004. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem, 37, 277-285.
• 31. Li H., Förstermann U., 2013. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease. Cur Opin Pharm, 13, 161-167.
• 32. Benter IF., Yousif MHM., Anim JT., Cojocel C., Diz DI., 2006. Angiotensin-(1–7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol Heart Circ Physiol, 290, 684-691.
• 33. Baradaran A., Nasri H., Rafieian-kopaei M., 2014. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants. J Res Med Sci, 19, 358-367.
• 34. Rodrigo R., Prat H., Passalacqua W., Araya J., Bachler JP., 2008. Decrease in oxidative stress through supplementation of vitamins C and E is associated with a reduction in blood pressure in patients with essential hypertension. Clin Sci, 114, 625-634.
• 35. Miguel-Carrasco JL., Monserrat Maria T., Mate A., Vazquez CM., 2010. Comparative effects of captopril and L-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats. Europ J Pharmacol, 632, 65-72.
• 36. Rajasekar P., Palanisamy N., Anuradha CV., 2007. Increase in nitric oxide and reductions in blood pressure, protein kinase C beta II and oxidative stress by L-carnitine: a study in the fructose-fed hypertensive rat. Clin Exp Hypertens, 29, 517-530.
• 37. Mate A., Miguel–Carrasco JL., Vazquez CM., 2010. The therapeutic prospects of using L-carnitine to manage hypertension-related organ damage. Drug Disc Tod, 15, 484-492.
• 38. Arduini A., Bonomini M., Savica V., Amato A., Zammit V., 2008. Carnitine in metabolic disease: potential for pharmacological intervention. Pharm Therap, 120, 149-156.
• 39. Gomez-Amores L., Mate A., Miguel-Carrasco JL., Jimenez L., Jos A., Camean AM., Revilla E., Santa-Maria C., Vazquez CM., 2007. L-carnitine attenuates oxidative stress in hypertensive rats. J Nutr Biochem, 18, 533-540.
• 40. Koeth RA., Wang Z., Levison BS., Buffa JA., Org E., Sheehy BT., Britt EB., Fu X., Wu Y., Li L., Smith JD., Di Donato JA., Chen J., Li H., Gary D Wu., Lewis JD., Warrier M., Brown JM., Krauss RM., Tang WHW., Bushman FD., Lusis AJ., Hazen SL., 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med, 19, 576-588.
• 41. Ferrari R., Merli, E., Cicchitelli G., Mele D., Fucili A., Ceconi C., 2004. Therapeutic Effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: A review. Annals NYA Sci, 1033, 79-91.
• 42. Shargorodsky M., Debby O., Matas Z., Zimlichman R., 2010. Effect of long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) on arterial compliance, humoral factors and inflammatory markers in patients with multiple cardiovascular risk factors. Nutr Metab, 7, 55.
• 43. Banach M., Serban C., Sahebkar A., Ursoniu S., Rysz J., Muntner P., Toth PP., Jones SR., Rizzo M., Glasser SP., Gregory YH., Dragan S, Mikhailidis DP., 2015. Effects of coenzyme Q10 on statin-induced myopathy: A meta-analysis of randomized controlled trials. Mayo Clin Proc, 90, 24-34.
• 44. Mortensen SA., Rosenfeldt F., Kumar A., Dolliner P., Filipiak KJ., Pella D., Alehagen .U, Steurer G., Littarru GP., 2014. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. J Am Coll Card Heart Failure, 2, 641-649.