Protective Effects of L-carnitine and Co-enzyme Q10 Against Oxidative Stress Damage in Hypertension

Abstract

In this study, it was aimed to investigate the effects of L-carnitine and Co-enzyme Q10 administration together with ACE Inhibitor (ACE inh.) on oxidative stress parameters in liver, brain and kidney tissues in L-NAME hypertensive rats. At the study, divided all rats into eight groups, four groups with 14 days of experiment time and four groups with 28 days of experiment time. At the end of the experiment, the rats were euthanized and their liver, brain and kidney tissues were taken. Malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) activities were measured in tissue supernatants. While NO and MDA levels increased in all tissues, a significant decrease was observed in GSH levels (P<0.001). In conclusion, it is suggested that supplementation of L-carnitine and CoQ10 can be considered as a combination therapy strategy for patients prone to higher levels of oxidative stress and inflammation.

Keywords

• ACE inhibitor
• Co-enzyme Q10
• hypertensive
• L-carnitine

Hipertansiyonda L-karnitin ve Ko-enzim Q10'un Oksidatif Stres Hasarına Karşı Koruyucu Etkileri

Abstract

Bu çalışmada, L-NAME hipertansif sıçanlarda ACE İnhibitörü (ACE inh.) ile birlikte L-carnitine ve Co-enzyme Q10 uygulamasının karaciğer, beyin ve böbrek dokularında oksidatif stres parametreleri üzerine etkilerinin araştırılması amaçlanmıştır. Çalışmada,14 günlük deney süresine sahip dört grup ve 28 günlük deney süresi sahip olan dört grup olmak üzere sekiz gruba ayrıldı. Deney sonunda sıçanlara ötenazi uygulanarak karaciğer, beyin ve böbrek dokuları alındı. Doku süpernatanlarında malondialdehit (MDA), glutatyon (GSH) ve nitrik oksit (NO) aktiviteleri ölçüldü. Tüm dokularda NO ve MDA seviyeleri yükselirken, GSH seviyelerinde belirgin bir düşüş gözlendi (P<0.001). Sonuç olarak L- karnitin ve CoQ10 takviyesinin, daha yüksek düzeyde oksidatif stres ve inflamasyona eğilimli hastalar için bir kom- binasyon tedavisi stratejisi olarak düşünülebileceği önerilmektedir.

Keywords

• ACE inhibitörü
• hipertansif
• koenzim Q10
• L-karnitin

References

1. Abdel-Emam RA, Ali MF. Effect of l-carnitine supplementation on lead acetate-induced liver cell apoptosis and inflammation: Role of caspase-3 and gly- cogen synthase kinase-3β enzymes. Life Sci 2022; 291: 120-277.
2. Adrogué HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med 2007; 356(19): 1966-78.
3. Alaedin M. Effect of an inflammatory stimulus on mitochondrial fun1ctionality in liver cells of dairy cows, Doctoral dissertation, Universitäts-und Landesbibliothek, Bonn 2021; 22-4.
4. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Miedema MD, Munoz D, Smith Jr SC, Virani SS, Williams SR KA, Ye- boah J, Ziaeian B. ACC/AHA guideline on the pri- mary prevention of cardiovascular disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 140(11): e596-e646.
5. Beutler E, Duron O, Kelly BM. Improved method for determination of blood glutathione. J Lab Clin Med 1963; 61: 882-8.
6. Bueno R, de Sotomayor MA, Perez-Guerrero C, Gomez-Amores L, Vazquez CM, Herrera MD. L- carnitine and propionyl-L-carnitine improve endo- thelial dysfunction in spontaneously hypertensive rats: different participation of NO and COX- products. Life Sci 2005; 77(17): 2082-97.
7. Cardoso AM, Martins CC, Fiorin, FDS, Schmatz R, Abdalla FH, Gutierres J, Zanini D, Fiorenza AM, Stefanello N, Serres JDS, Carvolho F, Castro VP, Mazzanti CM, Royes LFF, Bello-Klein A, Goularte JF, Morsch VM, Bagatini MD, Schetinger MRC. Physical training prevents oxidative stress in L- NAME-induced hypertension rats. Cell Biochem Funct 2013; 31(2): 136-51.
8. Demirdag K, Bahcecioglu IH, Ozercan IH, Özden M, Yilmaz S, Kalkan A. Role of L-carnitine in the pre- vention of acute liver damage induced by carbon tetrachloride in rats. J Gastroenterol Hepatol 2004; 19(3): 333-8.

9. Doggrell SA, Brown L. Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 1998; 39(1): 89-105.
10. Du Q, Liao Q, Chen C, Yang X, Xie, R, Xu J. The role of transient receptor potential vanilloid 1 in common diseases of the digestive tract and the cardiovascu- lar and respiratory system. Front Physiol 2019; 10: 1064.
11. Fielding R, Riede L, Lugo JP, Bellamine A. L- carnitine supplementation in recovery after exer- cise. Nutrients 2018; 10(3): 349.
12. Forouzanfar F, Asgharzade S. MicroRNAs in noise- induced hearing loss and their regulation by oxida- tive stress and inflammation. Curr Drug Targets 2020; 21(12): 1216-24.
13. Guerreiro G, Faverzani J, Jacques CED, Marchetti DP, Sitta A, de Moura Coelho D, Kayser A, Kok F, Athayde L, Manfredini V, Wajner M, Vargas CR. Oxidative damage in glutaric aciduria type I pa- tients and the protective effects of L‐carnitine treat- ment. J Cell Biochem 2018; 119(12): 10021-32.
14. Jaarin K, Foong WD, Yeoh MH, Kamarul ZYN, Qodri- yah HMS, Azman A, Zuhair JSF, Juliana AH, Kami- sah Y. Mechanisms of the anti-hypertensive effects of Nigella sativa oil in L-NAME-induced hyperten- sive rats. Clinics (Sao Paulo) 2015; 70(11): 751-7.
15. Khan SA, Choudhary R, Singh A, Bodakhe SH. hy- pertension potentiates cataractogenesis in rat eye through modulation of oxidative stress and electro- lyte homeostasis. J Curr Ophthalmol 2016; 28(3): 123-30.
16. Khosla P, Karan RS, Bhargava VK. Effect of garlic oil on ethanol induced gastric ulcers in rats. Phytother Res 2004; 18 (1): 87-91.
17. Labandeira-Garcia JL, Rodríguez-Perez AI, Garrido- Gil P, Rodriguez-Pallares J, Lanciego JL, Guerra MJ. Brain renin-angiotensin system and microglial polarization: Implications for aging and neuro- degeneration. Front Aging Neurosci 2017; 9: 129.
18. Maddu N. Diseases related to types of free radicals. Shalabay E. ed. In: Antioxidants. Rijeka, Croatia: IntechOpen, 2019; pp. 365-71.
19. Miranda KM, Espey MG, Wink DA. A Rapid, simple spectrophotometric method for simultaneous detec- tion of nitrate and nitrite. Nitric Oxide 2001; 5(1): 62 -71.
20. Mustafa HN, Hegazy GA, El Awdan SA, and Abdel- Baset M. Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in doxorubicin in- duced toxicity. Tissue Cell 2017; 49(3): 410-26.
21. Ozsoy SY, Ozsoy B, Ozyildiz Z, Aytekin I. Protective effect of L-carnitine on experimental lead toxicity in rats: A Clinical, histopathological and immunohisto- chemical study. Biotech Histochem 2011; 86(6): 436-43.
22. Perez-Lloret S, Otero-Losada M, Toblli JE, Capani F. Renin-angiotensin system as a potential target for new therapeutic approaches in Parkinson’s dis- ease. Expert Opin Investig Drugs 2017; 26(10): 1163-73.
23. Sadighara M, Joktaji JP, Hajhashemi V, Minaiyan M. Protective effects of Coenzyme Q10 and L- carnitine against statin-induced pancreatic mitochondrial toxicity in rats. Res Pharm Sci 2017; 12 (6): 434-43.
24. Sener G, Paskaloglu K, Satiroglu H, Alican İ, Kaçmaz A, Sakarcan A. L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardi- ovasc Pharmacol 2004; 43(5): 698-705.
25. Taşar N, Şehirli Ö, Yiğiner Ö, Süleymanoğlu S, Yüksel M, Yeğen B, Şener G. Protective effects of Nigella sativa against hypertension-induced oxidative stress and cardiovascular dysfunction in rats. Marmara Pharmaceutical Journal 2012; 16(2): 141- 9.
26. Thakur Y, Bharti R, Sharma R. Myths and reality of L- carnitine (3-Hydroxy 4-N trimethylammonium butyrate) supplementation and its chemistry: A systematic review. Materials Today: Proceedings. 2021; 48(5): 1277-82.
27. Ülker S, McMaster D, McKeown PP, Bayraktutan U. Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation. Cardiovasc Res 2003; 59(2): 488-500.
28. Vaziri ND, Ni Z, Oveisi F. Upregulation of renal and vascular nitric oxide synthase in young spontaneously hypertensive rats. Hypertension 1998; 1(6): 1248-54.
29. Yoshioka T, Kawada K, Shimada T, and Mori M. Lipid peroxidation in maternal and cord blood and pro- tective mechanism aganist activated-oxygen toxicity in the blood. Am J Obstet Gynecol 1979; 135(3): 372-6.
30. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk fac- tors associated with myocardial infarction in 52 Countries (the INTERHEART Study): Case-control Study. Lancet 2004; 364(9438): 937-52.