Sains Malaysiana 51(7)(2022):
2137-2146
http://doi.org/10.17576/jsm-2022-5107-16
Combined Antioxidant Formulation of Ascorbic Acid
with Resveratrol Ameliorates Isoproterenol-Induced
Myocardial Infarction in Rats
(Gabungan Formulasi Antioksidan Asid Askorbik dengan Resveratrol yang Ditambah Baik dengan Isoproterenol-Penginfarkan Miokardium Teraruh dalam Tikus)
HAICHAO GAO1, HONG WANG1,*, TINGTING HAN2, XIANSHENG HUANG1,
SHUCHENG LI1 & XIBING WANG1
1Department of Cardiology, Affiliated Hospital of
Chengde Medical College, No 36, Nanyingzi Street 067000, Chengde, Hebei Province, China
2Department of Emergency, The Third Central Hospital
of Tianjin, 300170 Tianjin, China
Received: 31 July 2021/Accepted: 7 December 2021
ABSTRACT
The current investigation was
proposed to assess the effectiveness of the combination of resveratrol and
ascorbic acid against Isoproterenol (ISO)-induced myocardial infarction in
rats. The experimental model was divided
into six groups (n = 6 in each group). Group I: control, Group 2: isoproterenol
(ISO)-100 mg/kg b.wt, Group 3: ISO+Resveratrol (RES) (20 mg/kg b.wt) treated, Group 4: ISO+ Ascorbic
acid (AA) (80 mg/kg b.wt) treated, Group 5: ISO+RES
(20 mg/kg b.wt)+AA (80 mg/kg b.wt)
treated and Group 6 : RES (20 mg/kg b.wt)+ AA (80 mg/kg b.wt) alone
treated. The study showed an increase in lipid peroxides and cardiac markers in
the serum samples of experimental animals administered with ISO. Treatment with
RES and AA individually and a combinational formulation brought a significant
decrease in lipid peroxides and cardiac markers. They increased the level of
enzymatic antioxidants and non-enzymatic antioxidant levels. Histopathological
results showed the distortion of heart architecture among the experimental
groups administered with ISO and significant recovery when treated with RES and
AA individually and in their combination. The study presents the effective
combination of RES and AA in combating ISO-induced myocardial infarction and
protection against ROS-mediated oxidative stress.
Keywords: Ascorbic acid; isoproterenol; myocardial
infarction; resveratrol
ABSTRAK
Penyelidikan ini dicadangkan untuk menilai keberkesanan gabungan resveratrol dan asid askorbik terhadap penginfarkan miokardium yang disebabkan oleh Isoproterenol (ISO) pada tikus. Model uji kaji dibahagikan kepada enam kumpulan (n = 6 dalam setiap kumpulan). Kumpulan I: kawalan, Kumpulan 2: isoproterenol
(ISO)-100 mg/kg b.wt, Kumpulan 3: ISO+Resveratrol (RES) (20 mg/kg b.wt) terawat,
Kumpulan 4: ISO+ Askorbik asid (AA) (80 mg/kg b.wt) terawat,
Kumpulan 5: ISO+RES (20 mg/kg b.wt)+AA (80 mg/kg b.wt) terawat dan Kumpulan 6 : RES (20 mg/kg b. wt)+ AA (80
mg/kg b.wt) sahaja terawat. Kajian menunjukkan peningkatan dalam peroksida lipid dan penanda jantung dalam sampel serum haiwan uji kaji yang telah diberi ISO. Rawatan dengan
RES dan AA secara individu dan gabungan formulasi membawa penurunan yang ketara
dalam peroksida lipid dan penanda jantung. Ia meningkatkan tahap antioksidan berenzim dan tahap antioksidan bukan berenzim. Keputusan histopatologi mendedahkan herotan arkitektur jantung dalam kalangan kumpulan uji kaji yang diadministrasi dengan ISO dan
pemulihan yang ketara apabila dirawat dengan RES dan AA secara individu dan secara gabungan. Kajian itu membentangkan gabungan RES dan AA
yang berkesan dalam memerangi penginfarkan miokardium yang disebabkan oleh
ISO dan perlindungan terhadap tekanan oksidatif pengantaraan ROS.
Kata kunci: Asid askorbik;
isoproterenol; penginfarkan miokardium;
resveratrol
REFERENCES
Abdel-Daim, M.M., Taha, R., Ghazy,
E.W. & El-Sayed, Y.S. 2016. Synergistic ameliorative effects of sesame oil
and alpha-lipoic acid against subacute diazinon toxicity in rats: Hematological,
biochemical, and antioxidant studies. Canadian
Journal of Physiology and Pharmacology 94(1): 81-88.
Aguilar-Alonso, P.,
Vera-Lopez, O., Brambila-Colombres, E., Segura-Badilla, O., Avalos-López, R.,
Lazcano-Hernández, M. & Navarro-Cruz, A.R. 2018. Evaluation of oxidative
stress in cardiomyocytes during the aging process in rats treated with
resveratrol. Oxidative Medicine and
Cellular Longevity 2018: 1390483.
Bagulho, A., Vilas-Boas,
F., Pena, A., Peneda, C., Santos, F.C., Jerónimo, A., de Almeida, R.F.M. &
Real, C. 2015. The extracellular matrix modulates H2O2 degradation and redox signaling in endothelial cells. Redox Biology 6: 454-460.
Bergmeyer, H.U. &
Gawehn, K. 1974. Methods of Enzymatic Analysis. New York: Academic Press. pp. 1-1194.
Beutler, E. & Kelly,
B.M. 1963. The effect of sodium nitrite on red cell GSH. Experientia 19(2): 96-97.
Bienert, G.P., Møller,
A.L.B., Kristiansen, K.A., Schulz, A., Møller, I.M., Schjoerring, J.K. &
Jahn, T.P. 2007. Specific aquaporins facilitate the diffusion of hydrogen
peroxide across membranes. Journal of
Biological Chemistry 282(2): 1183-1192.
Birben, E., Sahiner,
U.M., Sackesen, C., Erzurum, S. & Kalayci, O. 2012. Oxidative stress and
antioxidant defense. The World
Allergy Organization Journal 5(1): 9-19.
Bonnefont-Rousselot, D.
2016. Resveratrol and cardiovascular diseases. Nutrients 8(5): 250.
Buttros, J.B., Bergamaschi, C.T., Ribeiro, D.A., Fracalossi, A.C.C. &
Campos, R.R. 2009. Cardioprotective actions of ascorbic acid during
isoproterenol-induced acute myocardial infarction in rats. Pharmacology 84(1): 29-37.
Cheng, L., Jin, Z., Zhao, R., Ren, K., Deng, C. & Yu, S. 2015.
Resveratrol attenuates inflammation and oxidative stress induced by myocardial
ischemia-reperfusion injury: Role of Nrf2/ARE pathway. International Journal of Clinical and Experimental Medicine 8(7):
10420.
Dasgupta, B. & Milbrandt, J. 2007. Resveratrol stimulates AMP kinase
activity in neurons. In Proceedings of
the National Academy of Sciences. pp. 7217-7222.
de Lucia, C., Gambino, G., Petraglia, L., Elia, A., Komici, K.,
Femminella, G.D., D’Amico, M.L., Formisano, R., Borghetti, G., Liccardo, D. &
Nolano, M. 2018. Long-term caloric restriction improves cardiac function,
remodeling, adrenergic responsiveness, and sympathetic innervation in a model
of postischemic heart failure. Circulation:
Heart Failure 11(3): e004153.
Desai, I.D. 1984. Vitamin E analysis methods for animal tissues. In Methods in Enzymology, edited by Packer, L. Amsterdam:
Elsevier. pp. 138-147.
Feng, L., Ren, J., Li, Y., Yang, G., Kang, L., Zhang, S., Ma, C., Li,
J., Liu, J. & Yang, L. 2019. Resveratrol protects against Isoproterenol
induced myocardial infarction in rats through VEGF-B/AMPK/eNOS/NO signalling
pathway. Free Radical Research 53(1):
82-93.
Ferrari, R., Ceconi, C., Curello, S., Cargnoni, A., Alfieri, O.,
Pardini, A., Marzollo, P. & Visioli, O. 1991. Oxygen free radicals and
myocardial damage: Protective role of thiol-containing agents. The American Journal of Medicine 91(3):
S95-S105.
Gu, X.S., Wang, Z.B., Ye, Z., Lei, J.P., Li, L., Su, D.F. & Zheng,
X. 2014. Resveratrol, an activator of SIRT1, upregulates AMPK and improves
cardiac function in heart failure. Genetics
and Molecular Research 13(1): 323-335.
Habig, W.H., Pabst, M.J. & Jakoby, W.B. 1974. Glutathione
S-transferases. The first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry 249(22):
7130-7139.
Hashemzaei, M., Heravi, R.E., Rezaee, R., Roohbakhsh, A. & Karimi,
G. 2017. Regulation of autophagy by some natural products as a potential
therapeutic strategy for cardiovascular disorders. European Journal of Pharmacology 802: 44-51.
Jideani, A.I., Silungwe, H., Takalani, T., Omolola, A.O., Udeh, H.O.
& Anyasi, T.A. 2021. Antioxidant-rich natural fruit and vegetable products
and human health. International Journal of Food Properties 24(1): 41-67.
Kanamori, H., Takemura, G., Goto, K., Tsujimoto, A., Ogino, A.,
Takeyama, T., Kawaguchi, T., Watanabe, T., Morishita, K., Kawasaki, M., Mikami,
A., Fujiwara, T., Fujiwara, H., Seishima, M. & Minatoguchi, S. 2013.
Resveratrol reverses remodeling in hearts with large, old myocardial
infarctions through enhanced autophagy-activating AMP kinase pathway. The American Journal of Pathology 182(3):
701-713.
Karthick, M. & Prince, P.S.M. 2006. Preventive effect of rutin, a
bioflavonoid, on lipid peroxides and antioxidants in
isoproterenol‐induced myocardial infarction in rats. Journal of Pharmacy and Pharmacology 58(5): 701-707.
Kaspar, J.W., Niture, S.K. & Jaiswal, A.K. 2009. Nrf2: INrf2 (Keap1)
signaling in oxidative stress. Free
Radical Biology and Medicine 47(9): 1304-1309.
Kazmierczak-Baranska, J., Boguszewska, K., Adamus-Grabicka, A. &
Karwowski, B.T. 2020. Two faces of vitamin C-antioxidative and pro-oxidative
agent. Nutrients 12(5): 1501.
Kim, H., Kim, S., Han, S., Rane, P.P., Fox, K.M., Qian, Y. & Suh,
H.S. 2019. Prevalence and incidence of atherosclerotic cardiovascular disease
and its risk factors in Korea: A nationwide population-based study. BMC Public Health 19(1): 1112.
King, J. 1965. The dehydrogenase of oxidoreductase-lactate
dehydrogenase. Practical Clinical
Enzymology, edited by Van, D. London: Van Nostrand. pp. 93-193.
Kumar, M., Kasala, E.R., Bodduluru, L.N., Kumar, V. & Lahkar, M.
2017. Molecular and biochemical evidence on the protective effects of quercetin
in isoproterenol‐induced acute myocardial injury in rats. Journal of Biochemical and Molecular
Toxicology 31(1): 1-8.
McMichael, M. & Moore, R.M. 2004. Ischemia–reperfusion injury
pathophysiology, part I. Journal of
Veterinary Emergency and Critical Care 14(4): 231-241.
Misra, H.P. & Fridovich, I. 1972. The role of superoxide anion in
the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry 247(10):
3170-3175.
Moris, D., Spartalis, M., Tzatzaki, E., Spartalis, E., Karachaliou,
G.S., Triantafyllis, A.S., Karaolanis, G.I., Tsilimigras, D.I. &
Theocharis, S. 2017. The role of reactive oxygen species in myocardial redox
signaling and regulation. Annals of
Translational Medicine 5(16): 324.
Nasri, H., Baradaran, A., Shirzad, H. & Rafieian-Kopaei, M. 2014.
New concepts in nutraceuticals as alternative for pharmaceuticals. International Journal of Preventive Medicine 5(12): 1487-1499.
Nirmala, C. & Puvanakrishnan, R. 1996. Protective role of curcumin
against isoproterenol induced myocardial infarction in rats. Molecular and Cellular Biochemistry 159(2): 85-93.
Ohkawa, H., Ohishi, N. & Yagi, K. 1979. Assay for lipid peroxides in
animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95(2): 351-358.
Okinaka, S., Kumagai, H., Ebashi, S., Sugita, H., Momoi, H., Toyokura,
Y. & Fujie, Y. 1961. Serum creatine phosphokinase. Activity in progressive
muscular dystrophy and neuromuscular diseases. Arch. Neurol. 4: 520-525.
Omaye, S.T., Turnbull, J.D. & Sauberlich, H.E. 1979. [1] Selected
methods for the determination of ascorbic acid in animal cells, tissues, and
fluids. In Methods in Enzymology,
edited by McCormick, D.B. & Wright, L.D. Amsterdam: Elsevier. pp. 3-11.
Patel, V., Upaganlawar, A., Zalawadia, R. & Balaraman, R. 2010.
Cardioprotective effect of melatonin against Isoproterenol induced myocardial
infarction in rats: A biochemical, electrocardiographic and histoarchitectural
evaluation. European Journal of
Pharmacology 644(1-3): 160-168.
Qi, W., Boliang, W., Xiaoxi, T., Guoqiang, F., Jianbo, X. & Gang, W.
2020. Cardamonin protects against doxorubicin-induced cardiotoxicity in mice by
restraining oxidative stress and inflammation associated with Nrf2 signaling. Biomedicine & Pharmacotherapy 122:
109547.
Rhee, S.G., Woo, H.A. & Kang, D. 2018. The role of peroxiredoxins in
the transduction of H2O2 signals. Antioxidants & Redox Signaling 28(7): 537-557.
Riba, A., Deres, L., Sumegi, B., Toth, K., Szabados, E. & Halmosi,
R. 2017. Cardioprotective effect of resveratrol in a postinfarction heart
failure model. Oxidative Medicine and
Cellular Longevity 2017: 6819281.
Ribeiro, D.A., Buttros, J.B., Oshima, C.T.F., Bergamaschi, C.T. &
Campos, R.R. 2009a. Ascorbic acid prevents acute myocardial infarction induced
by Isoproterenol in rats: Role of inducible nitric oxide synthase production. Journal of Molecular Histology 40(2):
99-105.
Rimbaud, S., Ruiz, M., Piquereau, J., Mateo, P., Fortin, D., Veksler, V.,
Garnier, A. & Ventura-Clapier, R. 2011. Resveratrol improves survival,
hemodynamics and energetics in a rat model of hypertension leading to heart
failure. PLoS ONE 6(10): e26391.
Rotruck, J.T., Pope, A.L., Ganther, H.E., Swanson, A.B., Hafeman, D.G. &
Hoekstra, W.G. 1973. Selenium: Biochemical role as a component of glutathione
peroxidase. Science 179(4073):
588-590.
Sánchez-Hernández, C.D., Torres-Alarcón, L.A., González-Cortés, A. &
Peón, A.N. 2020. Ischemia/reperfusion injury: Pathophysiology, current clinical
management, and potential preventive approaches. Mediators of Inflammation 2020: 8405370.
Shah, Z.A., Li, R.C., Thimmulappa, R.K., Kensler, T.W., Yamamoto, M.,
Biswal, S. & Doré, S. 2007. Role of reactive oxygen species in modulation
of Nrf2 following ischemic reperfusion injury. Neuroscience 147(1): 53-59.
Shite, J., Qin, F., Mao, W., Kawai, H., Stevens, S.Y. & Liang, C.S.
2001. Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction
in tachycardia-induced cardiomyopathy. Journal
of the American College of Cardiology 38(6): 1734-1740.
Simpson, P.J. & Lucchesi, B.R. 1987. Free radicals and myocardial
ischemia and reperfusion injury. The
Journal of Laboratory and Clinical Medicine 110(1): 13-30.
Takahara, S., Hamilton, H.B., Neel, J.V., Kobara, T.Y., Ogura, Y. &
Nishimura, E.T. 1960. Hypocatalasemia: A new genetic carrier state. Journal of Clinical Investigation 39(4):
610-619.
Upaganlawar, A., Gandhi, C. & Balaraman, R. 2009. Effect of green
tea and vitamin E combination in isoproterenol induced myocardial infarction in
rats. Plant Foods for Human Nutrition 64(1): 75-80.
Venardos, K.M. & Kaye, D.M. 2007. Myocardial ischemia-reperfusion
injury, antioxidant enzyme systems, and selenium: A review. Current Medicinal Chemistry 14(14):
1539-1549.
Witte, K.K.A., Nikitin, N.P., Parker, A.C., Von Haehling, S., Volk,
H.D., Anker, S.D., Clark, A.L. & Cleland, J.G.F. 2005. The effect of
micronutrient supplementation on quality-of-life and left ventricular function
in elderly patients with chronic heart failure. European Heart Journal 26(21): 2238-2244.
Yogeeta, S.K., Gnanapragasam, A., Kumar, S.S., Subhashini, R., Sathivel,
A. & Devaki, T. 2006. Synergistic interactions of ferulic acid with
ascorbic acid: Its cardioprotective role during Isoproterenol induced
myocardial infarction in rats. Molecular
and Cellular Biochemistry 283(1): 139-146.
Zhu, H., Gao, M., Gao, X. & Tong, Y.
2018. Vascular endothelial growth factor-B: Impact on physiology and pathology. Cell Adhesion & Migration 12(3):
215-227.
*Corresponding author; email: cdwanghong666@sina.com
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