Sains Malaysiana 52(2)(2023): 563-578

http://doi.org/10.17576/jsm-2023-5202-18

Ameliorative Effects of Alpha Lipoic Acid, Quercetin and Ascorbic Acid against Zinc Oxide Nanoparticles Induced Hepatic Damage: In vivo

(Kesan Amelioratif Asid Alfa Lipoik, Kuersetin dan Asid Askorbik terhadap Nanozarah Zink Oksida Aruhan Kerosakan Hepar: In vivo)

SUMERA SAJJAD^1,*, LAIBA SAEED¹, HUSNA MALIK¹, BUSHRA NASEEM² FARZANA RASHID¹, IRAM LIAQAT, NIDA KHALID¹ & AMNA NASEEM¹

¹Department of Zoology, Lahore College for Women University

²Department of Chemistry, Lahore College for Women University

³Department of Zoology, Government College University, Lahore

Diserahkan: 29 April 2022/Diterima: 23 Disember 2022

Abstract

The current study envisioned to evaluate time related protective effect of quercetin, alpha lipoic acid and ascorbic acid on liver of mice against sub-acute exposure of zinc oxide (ZnO-NP) nanoparticle. Male Swiss albino mice (n=72) were randomly divided into eight groups (n=9, each group). G1 received saline solution 0.9%; G2 received quercetin (100 mg/kg b.w); G3 received alpha lipoic acid (100 mg/kg b.w); G4 received ascorbic acid (100 mg/kg b.w); G5 received ZnO-NPs (50 mg/kg b.w); G6 received ZnO-NPs with quercetin; G7 received ZnO-NPs with Alpha lipoic acid and G8 co-treated with ZnO-NPs and ascorbic acid for 21 consecutive days. Body weight, hepatosomatic index and plasma biochemical parameters (total protein, albumin, globulin, total cholesterol, triglycerides, high density lipoproteins, low density lipoprotein, aspartate aminotransferase, alanine transaminase, alkaline phosphatase & bilirubin) were estimated. ZnO showed significant increase in body weight and cause alterations in all biochemical parameters. Co-administration of quercetin (100 mg/kg b.w), alpha lipoic acid and ascorbic acid daily along with ZnO-NPs, significantly ameliorate the dramatic alteration in biochemical parameters and hepatocellular necrosis caused by ZnO nanoparticles. Brine shrimp larvae cytotoxicity assay of ZnO nanoparticles showed 0% mortality. Present study concluded that all three active ingredients showed hepatoprotective effects against nanoparticles induced time dependent toxicity.

Keywords: Alpha lipoic acid and ascorbic acid; quercetin; ZnO-NPs

Abstrak

Kajian ini berwawasan untuk menilai kesan perlindungan berkaitan masa kuersetin, asid alfa lipoik dan asid askorbik pada hati tikus terhadap pendedahan sub-akut nanozarah zink oksida (ZnO-NP). Tikus albino Swiss jantan (n=72) dibahagikan secara rawak kepada lapan kumpulan (n=9, setiap kumpulan). G1 menerima larutan garam 0.9%; G2 menerima kuersetin (100 mg/kg b.w); G3 menerima asid alfa lipoik (100 mg/kg b.w); G4 menerima asid askorbik (100 mg/kg b.w); G5 menerima ZnO-NPs (50 mg/kg b.w); G6 menerima ZnO-NPs dengan kuersetin; G7 menerima ZnO-NPs dengan asid alfa lipoik dan G8 dirawat bersama dengan ZnO-NPs dan asid askorbik selama 21 hari berturut-turut. Berat badan, indeks hepatosomatik dan parameter plasma biokimia (jumlah protein, albumin, globulin, jumlah kolesterol, trigliserida, lipoprotein ketumpatan tinggi, lipoprotein ketumpatan rendah, aminotransferase aspartat, transaminase alanin, fosfatase alkali & bilirubin) telah dianggarkan. ZnO menunjukkan peningkatan ketara dalam berat badan dan menyebabkan perubahan dalam semua parameter biokimia. Pemberian bersama kuercetin (100 mg/kg b.w), asid alfa lipoik dan asid askorbik setiap hari bersama-sama dengan ZnO-NPs dengan ketara memperbaiki perubahan dramatik dalam parameter biokimia dan nekrosis hepatosel yang disebabkan oleh nanozarah ZnO. Asai kesitotoksikan larva udang air garam nanozarah ZnO menunjukkan 0% kematian. Kajian ini menyimpulkan bahawa ketiga-tiga bahan aktif menunjukkan kesan hepatopelindung terhadap nanozarah aruhan ketoksikan bersandar-masa.

Kata kunci: Asid alfa lipoik; asid askorbik; kuersetin; ZnO-NPs

RUJUKAN

Abdel-Azim, S.A., Darwish, H.A., Rizk, M.Z., Ali, S.A. & Kadry, M.O. 2015. Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: Possible role of some antioxidants. Experimental and Molecular Pathology 67(4): 305-314.

Abdelbaky, N.A., Faddah, L.M., Al-Rasheed, N.M., Al-Rasheed, N.M. & Shebali, W. 2013. Role of quercetin and L-arginine in alleviating zinc oxide nanoparticle hepatotoxicity in rats. Chiang Mai Journal of Science 40(4): 577-592.

Abdel-Daim, M.M. 2014. Synergistic protective role of ceftriaxone and ascorbic acid against subacute diazinon-induced nephrotoxicity in rats. Cytotechnology 68(2): 279-289. doi: 10.1007/s10616-014-9779-z

Almansour, M., Sajti, L., Melhim, W. & Jarrar, B. 2015. Ultrastructural hepatic alterations induced by 35 nm zinc oxide nanoparticles. Nanoscience 7(9): 763-769.

Asaduzzaman, M., Rana, D.M.S., Hasan, S.M.R., Hossain, M. & Das, N. 2015. Cytotoxic (brine shrimp lethality bioassay) and antioxidant investigation of Barringtonia acutangula (L.). International Journal of Pharmaceutical Sciences Research 6(8): 1179-1185.

Ates, M., Daniels, J., Arslan, Z. & Farah, I.O. 2013a. Effects of aqueous suspensions of titanium dioxide nanoparticles on Artemia salina: Assessment of nanoparticle aggregation, accumulation and toxicity. Environmental Monitoring and Assessment 185(4): 3339-3348.

Ates, M., Danielsa, J., Arslana, Z., Farahb, I.O. & Rivera, H.F. 2013b. Comparative evaluation of impact of Zn and ZnO nanoparticles on brine shrimp (Artemia salina) larvae: Effects of particle size and solubility on toxicity. Environmental Science: Processes and Impacts 15(1): 225-233.

Bast, A. & Haenen, G.R. 2002. The toxicity of antioxidants and their metabolites. Environmental Toxicology and Pharmacology 11(3-4): 251-258.

Batley, G.E., Kirby, J.K. & McLaughlin, M.J. 2013. Fate and risks of nanomaterials in aquatic and terrestrial environments. Accounts of Chemical Research 46(3): 854-862.

Ben-Slama, I., Mrad, I., Rihane, N., El-Mir, L., Sakly, M. & Amara, S. 2015. Sub-acute oral toxicity of zinc oxide nanoparticles in male rats. Journal of Nanomedicine and Nanotechnology 6: 1-6.

Camiolo, G., Tibullo, D., Giallongo, C., Romano, A., Parrinello, N.L., Musumeci, G., Di Rosa, M., Vicario, N., Brundo, M.V., Amenta, F., Ferrante, M., Copat, C., Avola, R., Li Volti, G., Salvaggio, A., Di Raimondo, F. & Palumbo, G.A. 2019. α-Lipoic acid reduces iron-induced toxicity and oxidative stress in a model of iron overload. International Journal of Molecular Sciences 20(3): 609.

Choi, E.J., Chee, K.M. & Lee, B.H. 2003. Anti-and prooxidant effects of chronic quercetin administration in rats. European Journal of Pharmacology 482(1): 281-285.

Czerny, B., Put, A., Myśliwiec, Z. & Juzyszyn, Z. 2000. The influence of quercetin on some biochemical parameters in rats exposed to environmental contamination with fluorine compounds. Polish Journal of Environmental Studies 9(3): 157-161.

Drury, R.A.B. & Wallington, E.A. 1980. Carltons Histopathologic Technique. 5th ed. New York: Oxford University Press.

Esrefoglu, M., Cetin, A., Taslidere, E., Elbe, H., Ates, B., Tok, O.E. & Aydin, M.S. 2015. Therapeutic effects of melatonin and quercetin in improvement of hepatic steatosis in rats through suppression of oxidative damage. Bratislavske Lekarske Listy 118: 347-354.

Gnoni, G.V., Paglialonga, G. & Siculella, L. 2009. Quercetin inhibits fatty acid and triacylglycerol synthesis in rat-liver cells.  European Journal of Clinical Investigation  39(9): 761-768.

Gupta, R. & Xie, H.J. 2018. Nanoparticles in daily life: Applications, toxicity and regulations. Journal of Environmental Pathology, Toxicology and Oncology 37(3): 209-230.

Hong, T.K., Tripathy, N., Son, H.J., Ha, K.T., Jeong, H.S. & Hahn, Y.B. 2013. A comprehensive in vitro and in vivo study of ZnO nanoparticles toxicity. Journal of Materials Chemistry B 1(23): 2985-2992.

Jan, A., Azam, M., Siddiqui, K., Ali, A., Choi, I. & Haq, Q. 2015. Heavy metals and human health: Mechanistic insight into toxicity and counter defense system of antioxidants. The International Journal of Molecular Sciences 16(12): 29592-29630.

Jiang, Z.G., Mukamal, K., Tapper, E., Robson, S.C. & Tsugawa, Y. 2014. Low LDL-C and high HDL-C levels are associated with elevated serum transaminases amongst adults in the United States: A cross-sectional study. PLoS ONE 9(1): 1-8.

Jung, W.J. & Sung, M.K. 2004. Effects of major dietary antioxidant on inflammatory markers of RAW 264.7 macrophages. Biofactors 21: 113-117.

Kaya-Dagistanli, F., Tanriverdi, G., Altinok, A., Ozyazgan, S. & Ozturk, M. 2013. The effects of alpha lipoic acid on liver cells damages and apoptosis induced by polyunsaturated fatty acids. Food and Chemical Toxicology 53: 84-93.

Kessler, M., Ubeaud, G. & Jung, L. 2003. Anti- and pro-oxidant activity of rutin and quercetin derivatives. Journal of Pharmacy and Pharmacology 55(1): 131-142.

Khorsandi, L., Mansouri, E., Orazizadeh, M. & Jozi, Z. 2016. Curcumin attenuates hepatotoxicity induced by zinc oxide nanoparticles in rats. Bali Medical Journal 33(3): 252-257.

Kim, K.B., Kim, Y.W., Lim, S.K., Roh, T.H., Bang, D.Y., Choi, S.M., Lim, D.S., Kim, Y.J., Baek, S.H., Kim, M.K., Seo, H.S., Kim, M.H., Kim, H.S., Lee, J.Y., Kacew, S. & Lee, B.M. 2017. Risk assessment of zinc oxide, a cosmetic ingredient used as a UV filter of sunscreens. Journal of Toxicology and Environmental Health - Part B: Critical Reviews 20(3): 155-182.

Kunjathoor, V.V., Febbraio, M., Podrez, E.A., Moore, K.J., Andersson, L., Koehn, S., Rhee, J.S., Silverstein, R., Hoff, H.F. & Freeman, M.W. 2002. Scavenger receptors class AI/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. Journal of Biological Chemistry 277(51): 49982-49988.

Laher, I. 2011. Diabetes and alpha lipoic acid. Frontier Pharmacology 2(69): 1-15.

Ma, H., Williams, P.L. & Diamond, S.A. 2013. Ecotoxicity of manufactured ZnO nanoparticles: A review. Environmental Pollution 172: 76-85.

Mandal, S.K., Sil, K., Chatterjee, S., Ganguly, J., Chatterjee, K., Sarkar, P., Hazra, S. & Sardar, D. 2013. A study on lipid profiles in chronic liver diseases. National Journal of Medical Research 3(1): 1-3.

Miltonprabu, S., Tomczyk, M., Skalicka-Wozniak, K., Rastrelli, L., Daglia, M., Nabavi, S.F., Alavian, S.M. & Nabavi, S.M. 2017. Hepatoprotective effect of quercetin: From chemistry to medicine. Food and Chemical Toxicology 30: 1-10.

Mousavi, Z., Najafizadeh, P., Rezagholian, S., Rhamanifar, M.S. & Nosrati, N. 2016. Effects of subcutaneous injection MnO₂ micro- and nanoparticles on blood glucose level and lipid profile in rat. The Iranian Journal of Medical Sciences 41(6): 518-524.

Pari, L. & Murugavel, P. 2004. Protective effect of α-lipoic acid against cloroquine-induced hepatotoxicity in rats. Journal of Applied Toxicology 24(1): 21-26.

Peredo-Escárcega, A.E., Guarner-Lans, V., Pérez-Torres, I., Ortega-Ocampo, S., Carreón-Torres, E., Castrejón-Tellez, V., Díaz-Díaz, E. & Rubio-Ruiz, M.E. 2015. The combination of resveratrol and quercetin attenuates metabolic syndrome in rats by modifying the serum fatty acid composition and by upregulating SIRT 1 and SIRT 2 expression in white adipose tissue. Evidence-Based Complementary and Alternative Medicine 2015: 474032.

Rubins, H.B., Robins, S.J., Collins, D., Fye, C.L., Anderson, J.W., Elam, M.B., Faas, F.H., Linares, E., Schaefer, E.J., Schectman, G., Wilt, T.J. & Wittes, J. 1999. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. The New England Journal of Medicine 341(6): 410-418.

Selvakumar, K., Bavithra, S., Suganya, S., Ahmad Bhat, F., Krishnamoorthy, G. &  Arunakaran, J. 2013. Effect of quercetin on haematobiochemical and histological changes in the liver of polychlorinated biphenyls induced adult male Wistar rats. Journal of Biomarkers 2013: 960125.

Sharma, V., Singh, P., Pandey, A.K. & Dhawan, A. 2012a. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutation Research 745(1-2): 84-91.

Sharma, V., Singh, P., Pandey, A.K. & Dhawan, A. 2012b. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutation Research 745(1-2): 84-91.

Shireen, K., Pace, R., Mahboob, M. & Khan, A. 2008. Effects of dietary vitamin E, C and soybean oil supplementation on antioxidant enzyme activities in liver and muscles of rats. Food and Chemical Toxicology 46(10): 3290-3294.

Shrivastava, R., Bhargava, R. & Flora, S.J. 2014. Antioxidant activity and free radical scavenging potential of alpha lipoic acid and quercetin against Al₂O₃ nanoparticle-induced toxicity in mice. Free Radicals and Antioxidants 4(1): 8-14.

Skorupa, A., Michalkiewicz, S. & Jakubczyk, M. 2021. Highly sensitive determination of α-lipoic acid in pharmaceuticals on a boron-doped diamond electrode. Open Chemistry 19(1): 843-854.

Sminorff, N. & Wheeler, G.L. 2000. Ascorbic acid in plants biosynthesis and function. Critical Reviews in Biochemistry and Molecular Biology 35(4): 291-314.

Srivastava, M. & Yadav, R.S. 2007. Principles of Laboratory Techniques and Methods. 1st ed. Lucknow: International Book Distributing Company. p. 249.

Symonowicz, M. & Kolanek, M. 2012. Flavonoids and their properties to form chelate complexes. International Journal of Biotechnology and Food Science 76: 35-41.

Tourinho, P.S., Van Gestel, C.A., Lofts, S., Svendsen, C., Soares, A.M. & Loureiro, S. 2012. Metal-based nanoparticles in soil: Fate, behavior, and effects on soil invertebrates. Environmental Toxicology and Chemistry 31(8): 1679-1692.

Vaziri, N.D. 2003. Molecular mechanisms of lipid disorders in nephrotic syndrome. Kidney International 63(5): 1964-1976.

Wang, B., Feng, W., Wang, M., Wang, T., Gu, Y., Zhu, M., Ouyang, H., Shi, J., Zhang, F., Zhao, Y., Chai, Z., Wang, H. & Wang, J. 2008. Acute toxicological impact of nano- and submicro scaled zinc oxide powder on healthy adult mice. Journal of Nanoparticle Research 10(2): 263-276.

Wang, J., Zhou, G., Chen, C., Yu, H., Wang, T., Ma, Y., Jia, G., Gao, Y., Li, B., Sun, J., Li, Y., Jiao, F., Zhao, Y. & Chai, Z. 2007. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicology Letters 168(2): 176-185.

Yan, Z., Wang, W., Wu, Y., Wang, W., Li, B., Liang, N. & Wu, W. 2017. Zinc oxide nanoparticle-induced atherosclerotic alterations in vitro and in vivo. International Journal of Nanomedicine 12: 4433-4442.

Zou, H., Liu, X., Han, T., Hu, D., Yuan, Y., Gu, J., Bian, J. & Liu, Z. 2015. Alpha-lipoic acid protects against cadmium-induced hepatotoxicity via calcium signalling and gap junctional intercellular communication in rat hepatocytes. The Journal of Toxicological Sciences 40(4): 469-477.

^*Pengarang untuk surat-menyurat; email: drsumerasajjad786@gmail.com