Author(s): Moath Alqaraleh, Violet Kasabri, Ibrahim Al-Majali, Ahmad Aljaafreh, Nihad Al-Othman, K. Khleifat, Nafe M Al‐Tawarah, Haitham Qaralleh, Alia S. Khwaldeh, Sundus Alalawi, Mohammad al majali


DOI: 10.52711/0974-360X.2021.00677   

Address: Moath Alqaraleh1*, Violet Kasabri2, Ibrahim Al-Majali3, Ahmad Aljaafreh3, Nihad Al-Othman4, K. Khleifat5, Nafe M Al‐Tawarah3, Haitham Qaralleh3, Alia S. Khwaldeh6, Sundus Alalawi2, Mohammad al majali7
1Pharmacological and Diagnostic Research Center (PDRC), Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan.
2Department of Pharmacy, Faculty of Pharmacy. The University of Jordan, Amman, Jordan.
3Department of Medical Analysis, Mutah University, Mutah, Karak, 61710, Jordan.
4Division of Anatomy, Biochemistry, and Genetics. Faculty of Medicine and Health Sciences, An-Najah National University, Nablus.
5Department of Biology, Mutah University, Karak, Mutah, 61710 Jordan.
6Department of Medical Laboratory Sciences, Faculty of Pharmacy, Jadara University, Irbid, Jordan.
7Department of Biological Sciences, Faculty of Science. The University of Jordan, Amman, Jordan.
*Corresponding Author

Published In:   Volume - 14,      Issue - 7,     Year - 2021

Background and aims: Branched chain amino acids (BCAAs) can be tightly connected to metabolism syndrome (MetS) which can be counted as a metabolic indicator in the case of insulin resistance (IR). The aim of this study was to assess the potential role of these acids under oxidative stress. Material and Methods: the in vitro antioxidant activity of BCAAs was assessed using free radical 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging assays. For further check, a qRT-PCR technique was madefor detection the extent of alterations in gene expression of antioxidative enzymes (catalase and glutathione peroxidase (Gpx)) in lipopolysaccharides (LPS(-induced macrophages RAW 264.7 cell line. Additionally, BCAAs antioxidant activity was evaluated based on plasma H2O2 levels and xanthine oxidase (XO) activity in prooxidative LPS-treated mice. Results: Different concentrations of BCAAs affected on DPPH radical scavenging activity but to lesser extent than the ascorbic acid. Besides, BCAAs obviously upregulated the gene expression levels of catalases and Gpx in LPS-modulated macrophage RAW 264.7 cell line. In vivo BCAAs significantly minimized the level of plasma H2O2 as well as the activity of XO activity under oxidative stress. Conclusion: our current findings suggest that BCAAs supplementation may potentially serve as a therapeutic target for treatment of oxidative stress occurs with atherosclerosis, IR-diabetes, MetS and tumorigenesis.

Cite this article:
Moath Alqaraleh, Violet Kasabri, Ibrahim Al-Majali, Ahmad Aljaafreh, Nihad Al-Othman, K. Khleifat, Nafe M Al‐Tawarah, Haitham Qaralleh, Alia S. Khwaldeh, Sundus Alalawi, Mohammad al majali. Branched chain amino Acids as in vitro and in vivo Anti-Oxidation Compounds. Research Journal of Pharmacy and Technology. 2021; 14(7):3899-4. doi: 10.52711/0974-360X.2021.00677

Moath Alqaraleh, Violet Kasabri, Ibrahim Al-Majali, Ahmad Aljaafreh, Nihad Al-Othman, K. Khleifat, Nafe M Al‐Tawarah, Haitham Qaralleh, Alia S. Khwaldeh, Sundus Alalawi, Mohammad al majali. Branched chain amino Acids as in vitro and in vivo Anti-Oxidation Compounds. Research Journal of Pharmacy and Technology. 2021; 14(7):3899-4. doi: 10.52711/0974-360X.2021.00677   Available on:

1.    Liemburg- Apers, D.C., et al.: Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Archives of Toxicology. 2015; 89(8): p. 1209-1226.
2.    Granger, D.N. and P.R. Kvietys: Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biology. 2015; 6: p. 524-551.
3.    Battelli, M.G., et al.: Xanthine oxidoreductase- derived reactive species: physiological and pathological effects. Oxidative Medicine and Cellular Longevity. 2016; 2016.
4.    Bravard, A., et al.: Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice. American Journal of Physiology-Endocrinology and Metabolism 2011; 300(3): p. E581-E591.
5.    Das, J., V. Vasan, and P.C. Sil: Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis. Toxicology and Applied Pharmacology. 2012; 258(2): p. 296-308.
6.    Jung, U.J. and M.-S. Choi: Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. International Journal of Molecular Sciences. 2014; 15(4): p. 6184-6223.
7.    Tangvarasittichai, S.: Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World Journal of Diabetes. 2015; 6(3): p. 456.
8.    Bhattacharyya, A., et al.: Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological Reviews. 2014; 94(2): p. 329-354.
9.    Monirujjaman, M. and A. Ferdouse: Metabolic and physiological roles of branched-chain amino acids. Advances in Molecular Biology. 2014; 2014.
10.    Giesbertz, P. and H. Daniel: Branched-chain amino acids as biomarkers in diabetes. Current Opinion in Clinical Nutrition and Metabolic Care. 2016; 19(1): p. 48-54.
11.    Alqaraleh, M., et al.: Branched amino acids as potential biomarkers in metabolic syndrome patients and as hypolipidemic compounds. Eur Asian Journal of Bio Sciences. 2019; 13(2): p. 2233-2241.
12.    Alqaraleh, M., V. Kasabri, and N. Al-Othman: Evaluation of pancreatic and extra pancreatic effects of branched amino acids. Romanian Journal of Diabetes Nutrition and Metabolic Diseases 2019; 26(2): p. 199-209.
13.    Ghimeray, A.K., et al.: Evaluation of Antioxidant and Anti-Inflammatory Effect of Rhododendron brachycarpum Extract Used in Skin Care Product by in Vitro and in Vivo Test. Technology and Investment. 2015; 6(02): p. 105.
14.    Khalaf, N.A., et al.: Antioxidant activity of some common plants. Turkish Journal of Biology. 2008; 32(1): p. 51-55.
15.    Huang, J., et al.: Anti-inflammatory oleanolic triterpenes from Chinese Acorns. Molecules. 2016; 21(5): p. 669.
16.    Litchfield, J.A. and F. Wilcoxon: A simplified method of evaluating dose-effect experiments. Journal of Pharmacology and Experimental Therapeutics. 1949; 96(2): p. 99-113.
17.    Abdel-Salam, O., N. Mohamed, and A. A. Sleem, The effects of trimetazidine on lipopolysaccharide-induced oxidative stress in mice. Vol. 10. 2011.
18.    D'Antona, G., et al.: Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metabolism. 2010; 12(4): p. 362-372.
19.    Kabanov, D. and I. Prokhorenko: Structural analysis of lipopolysaccharides from Gram-negative bacteria. Biochemistry (Moscow). 2010; 75(4): p. 383-404.
20.    Gutsmann, T., A.B. Schromm, and K. Brandenburg: The physicochemistry of endotoxins in relation to bioactivity. International Journal of Medical Microbiology. 2007; 297(5): p. 341-352.
21.    Victor, V.M., M. Rocha, and M. De la Fuente: Immune cells: free radicals and antioxidants in sepsis. International Immunopharmacology. 2004; 4(3): p. 327-347.
22.    Kallapura, G., et al.: Mechanisms involved in lipopolysaccharide derived ROS and RNS oxidative stress and septic shock. Journal of Microbiology Research and Reviews. 2014; 2(1): p. 6-11.
23.    Rada, B. and T.L. Leto, Oxidative innate immune defenses by Nox/Duox family NADPH oxidases, in Trends in Innate Immunity. 2008, Karger Publishers. p. 164-187.
24.    Díaz- Muñoz, M.D., et al.: Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages. Biochemical Journal. 2012; 443(2): p. 451-461.
25.    Suntres, Z.E. and P.N. Shek: Treatment of LPS-induced tissue injury: role of liposomal antioxidants. Shock (Augusta, Ga.). 1996; 6: p. S57-64.
26.    Takata, J., et al.: Water-soluble prodrug of vitamin E for parenteral use and its effect on endotoxin-induced liver toxicity. Biological and Pharmaceutical Bulletin. 1997; 20(2): p. 204-209.
27.    Berg, B.M., et al.: α-Tocopherol attenuates lipopolysaccharide-induced sickness behavior in mice. Brain, Behavior, and Immunity. 2004; 18(2): p. 149-157.
28.    Behrend, L., G. Henderson, and R. Zwacka, Reactive oxygen species in oncogenic transformation. 2003, Portland Press Limited.
29.    Benhar, M., et al.: Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress. Molecular and Cellular Biology. 2001; 21(20): p. 6913-6926.
30.    Hayden, M.S. and S. Ghosh: Shared principles in NF-κB signaling. Cell. 2008; 132(3): p. 344-362.
31.    Ryan, K.A., et al.: Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-κB and interleukin-8 expression. Infection and Immunity. 2004; 72(4): p. 2123-2130.
32.    Sajadimajd, S. and M. Khazaei: Oxidative stress and cancer: the role of Nrf2. Current cancer drug targets 2018; 18(6): p. 538-557.
33.    Civitarese, A.E., et al.: Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Medicine. 2007; 4(3): p. e76.
34.    Ristow, M., et al.: Antioxidants prevent health-promoting effects of physical exercise in humans. Proceedings of the National Academy of Sciences. 2009; 106(21): p. 8665-8670.
35.    Choi, H.-I., et al.: PGC-1α attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38 in HK-2 Cells. Scientific Reports. 2017; 7(1): p. 4319.
36.    Zhenyukh, O., et al.: High concentration of branched-chain amino acids promotes oxidative stress, inflammation and migration of human peripheral blood mononuclear cells via mTORC1 activation. Free Radical Biology and Medicine. 2017; 104: p. 165-177.
37.    Zemel, M.B., et al.: Effects of dairy compared with soy on oxidative and inflammatory stress in overweight and obese subjects. The American Journal of Clinical Nutrition. 2009; 91(1): p. 16-22.
38.    Liang, C., et al.: Leucine modulates mitochondrial biogenesis and SIRT1-AMPK signaling in C2C12 myotubes. Journal of Nutrition and Metabolism. 2014; 2014.
39.    Zhang, W., et al.: Sirt1 inhibits oxidative stress in vascular endothelial cells. Oxidative Medicine and cellular Longevity. 2017; 2017.s
40.    Matsuda, M. and I. Shimomura: Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Reviews in Endocrine and Metabolic Disorders. 2014; 15(1): p. 1-10.
41.    Hagiwara, A., M. Nishiyama, and S. Ishizaki: Branched‐chain amino acids prevent insulin‐induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2‐dependent mechanisms. Journal of Cellular Physiology. 2012; 227(5): p. 2097-2105.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles