Inhibitory activity of nanoencapsulated quercetin against sodium arsenite-induced sub-acute liver toxicity in rats
Abstract
Arsenic, a metalloid toxicant, is associated with a major global health problem as oxidative stress, a prime cause of tissue toxicity. The subject of our investigation was to assess the therapeutic efficiency of nanoencapsulated quercetin (QC) in combating sodium arsenite (NaAsO2)-inducted sub-acute hepatocellular toxicity in rat model. The rats of the hepatic damage group were injected subcutaneously (s.c.) four dosages of NaAsO2 (92.36 µM/kg b.wt.) twice a week. The rats of the polylactide nanoencapsulated QC group were injected intravenously (i.v.) four doses of nanoencapsulated QC (8.97 µmol/kg b.wt.) twice a week 2 h after the treatment (s.c.) with 92.36 µM /kg b. wt. NaAsO2 twice a week for four doses. The rats of the empty nanocasule or free QC treated group were injected i.v. four doses empty nanocapsule or free QC twice a week 2 h after the treatment (s.c.) with same doses of NaAsO2 twice a week for four doses. Arsenic deposition (580±20 µg/g protein) observed in liver tissue of rats treated with arsenite (92.36 µM/kg b.wt.), was found to reduce (120±9 µg/g protein) by the treatment of nanoencapsulated QC in rats significantly (p<0.001). The levels of antioxidant enzymes and GSSG/GSH ratio enhanced (p<0.001/0.1/0.01) by the treatment of NaAsO2 were reduced by the post treatment of nanoencapsulated QC significantly (p<0.001/0.01). The levels of ROS, lipohydroperoxide or membrane microviscosity increased or decreased (p<0.001) by the treatment of NaAsO2 were monitored to reduce or enhance significantly (p<0.001) by the treatment of nanoencapsulated QC in rat liver respectively. The blood serum biochemical levels enhanced (p<0.001) by the treatment of NaAsO2 were found to reduce significantly (p<0.001) by the treatment of nanoencapsulated QC in rats. The TGFβ1 and MMP-13 in the rat plasma augmented (p<0.001) by the treatment of NaAsO2-exposure were found to decline (p<0.001) significantly by the treatment of nanoencapsulated QC in rats. The rats in the other groups such as empty nanocapsule or free QC treated showed no or less inhibitory efficiency against NaAsO2-treatment compared to nanoencapsulated QC treated group. Application of nanoencapsulated QC may be a potent formulation to get higher inhibitory therapeutic efficiency against NaAsO2-induced sub-acute hepatocellular toxicity.
Keywords:
Arsenic, Sub-acute hepatocellular toxicity, Oxidative stress, Nanoencapsulated QC, Inhibitory therapeutic efficiencyDOI
https://doi.org/10.22270/jddt.v14i11.6835References
1. Argos M, Kalra T, Rathouz PJ, Chen Y, Pierce B, Parvez F, et al. Arsenic exposure from drinking water, and all-cause and chronic disease mortalities in Bangladesh (HEALS): A prospective cohort study. Lancet. 2010; 376(9737):252-58. https://doi.org/10.1016/S0140-6736(10)60481-3 PMid:20646756
2. Abdul KS, Jayasinghe SS, Chandana EP, Jayasumana C, De Silva PM. Arsenic and human health effects: A review. Environ Toxicol Pharmacol. 2015; 40:828-46. https://doi.org/10.1016/j.etap.2015.09.016 PMid:26476885
3. Karagas MR, Tosteson TD, Blum J, Morris JS, Baron JA, Klaue B. Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population. Environ Health Perspect. 1998; 106:1047-50. https://doi.org/10.1289/ehp.98106s41047 PMid:9703491 PMCid:PMC1533320
4. Carlin DJ, Naujokas MF, Bradham KD, Cowden J, Heacock M, Henry HF, et al. Arsenic and environmental health: State of the science and future research opportunities. Environ Health Perspect. 2016; 124:890-9. https://doi.org/10.1289/ehp.1510209 PMid:26587579 PMCid:PMC4937867
5. Seow WJ, Pan WC, Kile ML, Baccarelli AA, Quamruzzaman Q, Rahman M, et al. Arsenic reduction in drinking water and improvement in skin lesions: A follow-up study in Bangladesh. Environ Health Perspect. 2012; 120(12):1733-38. https://doi.org/10.1289/ehp.1205381 PMid:23060367 PMCid:PMC3548283
6. Wang W, Wang Q, Zou Z, Zheng F, Zhang A. Human arsenic exposure and lung function impairment in coal-burning areas in Guizhou. China Ecotoxic Environ Saf. 2020; 190:110174. https://doi.org/10.1016/j.ecoenv.2020.110174 PMid:31927192
7. Zeng Q, Zou Z, Wang Q, Sun B, Liu Y, Liang B, et al. Association and risk of five miRNAs with arsenic-induced multiorgan damage. Sci Total Environ. 2019; 680:1-9. https://doi.org/10.1016/j.scitotenv.2019.05.042 PMid:31085440
8. Saint-Jacques N, Brown P, Nauta L, Boxall J, Parker L, Dummer TJB. Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada. Environ Int. 2018; 110:95-104.https://doi.org/10.1016/j.envint.2017.10.014 PMid:29089168
9. Pichler G, Grau-Perez M, Tellez-Plaza M, Umans J, Best L, Cole S, et al. Association of arsenic exposure with cardiac geometry and left ventricular function in young adults. Circ Cardiovasc Imaging. 2019; 12(5):e009018. https://doi.org/10.1161/CIRCIMAGING.119.009018 PMid:31060373 PMCid:PMC6668025
10. Dangleben NL, Skibola CF, Smith MT. Arsenic immunotoxicity: A review. Environ Health. 2013; 12(1):73. https://doi.org/10.1186/1476-069X-12-73 PMid:24004508 PMCid:PMC3848751
11. Sodhi KK, Kumar M, Agrawal PK, Singh DK. Perspectives on arsenic toxicity, carcinogenicity and its systemic remediation strategies. Environ Technol Innov. 2019; 16(1):100462. https://doi.org/10.1016/j.eti.2019.100462
12. Aposhian HV, Aposhian MM. Newer developments in arsenic toxicity. J Am Coll Toxicol. 1989; 8:1297-305. https://doi.org/10.3109/10915818909009121
13. Ratnaike RN. Acute and chronic arsenic toxicity. Postgraduate Med J. 2003; 79:391-6. https://doi.org/10.1136/pmj.79.933.391 PMid:12897217 PMCid:PMC1742758
14. Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, et al. Arsenic: Toxicity, oxidative stress and human disease. J Appl Toxicol. 2011; 31:95-107. https://doi.org/10.1002/jat.1649 PMid:21321970
15. Watanabe T, Hirano S. Metabolism of arsenic and its toxicological relevance. Arch Toxicol. 2013; 87:969-79. https://doi.org/10.1007/s00204-012-0904-5 PMid:22811022
16. Lindberg AL, Kumar R, Goessler W, Thirumaran R, Gurzau E, Koppova K, et al. Metabolism of low-dose inorganic arsenic in a central European population: Influence of sex and genetic polymorphisms. Environ Health Perspect. 2007; 115:1081-6. https://doi.org/10.1289/ehp.10026 PMid:17637926 PMCid:PMC1913583
17. Mittal M, Flora SJ. Vitamine E supplementation protects oxidative stress during arsenic and fluoride antagonism in male mice. Drug Chem Toxicol. 2007; 30:263-81. https://doi.org/10.1080/01480540701380075 PMid:17613011
18. Liu J, Liv Y, Goyer RA, Achanzar W, Waalkes MP. Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oral or injected inorganic arsenicals. Toxicol Sci. 2000; 55:460-7. https://doi.org/10.1093/toxsci/55.2.460 PMid:10828279
19. Ramirez P, DelRazo LM, Gutierrez-Ruiz MC, Gonsebatt ME. Arsenite induces DNA-protein crosslinks and cytokeratin expression in the WRL-68 human hepatic cell line. Carcinogenesis. 2000; 21:701-6 .https://doi.org/10.1093/carcin/21.4.701 PMid:10753206
20. Hu Y, Li J, Lou B, Wu R, Wang G, Lu C, et al. The role of reactive oxygen species in arsenic toxicity. Biomolecules. 2020; 10(2):240. https://doi.org/10.3390/biom10020240 PMid:32033297 PMCid:PMC7072296
21. Silva CS, Kudlyk T, Tryndyak VP, Twaddle NC, Robinson B, Gu Q, et al. Gene expression analyses reveal potential mechanism of inorganic arsenic-induced apoptosis in zebrafish. J Appl Toxicol. 2023; 43(12):1872-82. https://doi.org/10.1002/jat.4520 PMid:37501093
22. Pace C, Dagda R, Angenmann J. Antioxidants protect against arsenic induced mitochondrial cardio-toxicity. Toxics. 2017; 5(4):38. https://doi.org/10.3390/toxics5040038 PMid:29206204 PMCid:PMC5750566
23. Shabir I, Pandey VK, Shams R, Dar AH, Dash KK, Khan SA, et al. Promising bioactive properties of quercetin for potential food applications and health benefits: A review. Front Nutr. 2022; 9:999752. https://doi.org/10.3389/fnut.2022.999752 PMid:36532555 PMCid:PMC9748429
24. Liu Z, Ren Z, Zhang J, Chuang CC, Kandaswamy E, Zhou T, et al. Role of ROS and nutritional antioxidants in human diseases. Front Physiol. 2018; 9:477. https://doi.org/10.3389/fphys.2018.00477 PMid:29867535 PMCid:PMC5966868
25. Das N, Bachhawat BK, Mahato SB, Basu MK. Plant glycosides in liposomal drug delivery system. Biochem J. 1987; 247:359-61. https://doi.org/10.1042/bj2470359 PMid:3426542 PMCid:PMC1148416
26. Jiang Q, Yin J, Chen J, Ma X, Wu M, Liu G, et al. Mitochondria targeted antioxidants: A step towards disease treatment. Oxid Med Cell Longev. 2020; 2020:8837893. https://doi.org/10.1155/2020/8837893 PMid:33354280 PMCid:PMC7735836
27. Purohit D, Jalwal P, Manchanda D, Saini S, Verma R, Kaushik D, et al. Nanocapsules: An emerging drug delivery system. Recent Pat Nanotechnol. 2023; 17(3):190-207. https://doi.org/10.2174/1872210516666220210113256 PMid:35142273
28. Hoff J, Rlatg LVT. Methods of blood collection in the mouse. Lab Anim. 2000; 29(10):47-53.
29. Tyagi R, Lala S, Verma AK, Nandy AK, Mahato SB, Maitra A, et al. Targeted delivery of arjunglucoside 1 using surface hydrophilic and hydrophobic nanocarriers to combat experimental leishmaniasis. J Drug Target. 2005; 13:161-71. https://doi.org/10.1080/10611860500046732 PMid:16036304
30. Karim S, Bhandari U, Kumar H, Salam A, Siddiqui MAA, Pillai KK. Doxorubicin induced cardiotoxicity and its modulation by drugs. Ind J Pharm. 2001; 33:203-7.
31. Beyer JWF, Fridovich I. Assaying for superoxide dismutase activity: Some large consequences of minor changes in conditions. Anal Biochem. 1987; 161(2):559-66. https://doi.org/10.1016/0003-2697(87)90489-1 PMid:3034103
32. Mandal AK, Das S, Mitra M, Chakrabarti RN, Chatterjee M, Das N. Vesicular flavonoid in combating diethylnitrosamine induced hepatocarcinoma in rat mode. J Exp Ther Oncol. 2008; 7:123-33.
33. Moragon AC, DeLucas GN, Encarnacion LFM, Rodriguez MAS, Jimenez FJA. Antioxidant enzymes, occupational stress and burnout in workers of a prehospitalary emergency service. Eur J Emerg Med. 2005; 12:111-15. https://doi.org/10.1097/00063110-200506000-00003 PMid:15891442
34. Sarkar S, Das N. Mannosylated liposomal flavonoid in combating age-related ischemis-reperfusion induced oxidative damage in rat brain. Mech Ageing Dev. 2006; 127:391-97. https://doi.org/10.1016/j.mad.2005.12.010 PMid:16480758
35. Castro VM, Soderstrom M, Carlberg I, Widersten M, Platz A, Mannervik B. Differences among human tumor cell lines in the expression of glutathione transferases and other glutathione-linked enzymes. Carcinogenesis. 1990; 11:1569-76. https://doi.org/10.1093/carcin/11.9.1569 PMid:2401046
36. Maiti S, Chatterjee AK. Differential response of cellular antioxidant mechanism of liver and kidney to arsenic exposure and its relation to dietary protein deficiency. Environ Toxicol Pharmacol. 2000; 8:227-35. https://doi.org/10.1016/S1382-6689(00)00046-6 PMid:10996542
37. Mandal AK, Das N. Sugar coated liposomal flavonoid: A unique formulation in combating carbon tetrachloride induced hepatic oxidative damage. J Drug Target. 2005; 13:305-15. https://doi.org/10.1080/10611860500230278 PMid:16199374
38. Betainder C, Fontaine E, Keriel C, Leuerve XM. Determination of mitochondrial oxygen species: Methodological aspects. J Cell Mol Med. 2002; 6:175-87. https://doi.org/10.1111/j.1582-4934.2002.tb00185.x PMid:12169203 PMCid:PMC6740075
39. Mandal AK, Sinha J, Mandal S, Mukhopadhyay S, Das N. Targeting of liposomal flavonoid to liver in combating hepatocellular oxidative damage. Drug Deliv. 2002; 9:181-85. https://doi.org/10.1080/15227950290097615 PMid:12396735
40. Lowry OH, Rosebrough NJ, Farr AL, Randel RG. Protein measurement with Folin Phenol reagent. J Biol Chem. 1951; 193:265-77. https://doi.org/10.1016/S0021-9258(19)52451-6 PMid:14907713
41. Sarkar S, Mandal S, Sinha J, Mukhopadhyay S, Das N, Basu MK. Quercetin: Critical evaluation as an anti leishmanial agent in vivo in hamsters using different vesicular delivery modes. J Drug Target. 2002; 10:573-78. https://doi.org/10.1080/106118021000072681 PMid:12683660
42. Guha Mazumder DN, De BK, Santra A, Ghosh N, Das S, Lahiri S, et al. Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water. Clin Toxicol. 2001; 39:665-74. https://doi.org/10.1081/CLT-100108507 PMid:11778664
43. Li L, Lei X, Chen L, Ma Y, Luo J, Liu X, et al. Protective mechanism of quercetin compounds against acrylamide-induced hepatotoxicity. Food Sci Human Wellness. 2024; 13(1):225-40. https://doi.org/10.26599/FSHW.2022.9250019
44. Das S, Santra A, Lahiri S, Guha Mazumder DN. Implications of oxidative stress and hepatic cytokine (TNF-alpha and IL-6) mresponse in the pathogenesis of hepatic collagenesis in chronic arsenic toxicity. Toxicol Appl Pharmacol. 2005; 204:18-26. https://doi.org/10.1016/j.taap.2004.08.010 PMid:15781290
45. Aherne SA, Brien'O NM. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide-and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med. 2000; 29(6):507-14. https://doi.org/10.1016/S0891-5849(00)00360-9 PMid:11025194
46. Roeb E. Matrix metalloproteinases and liver fibrosis (translational aspects). Matrix Biol. 2018; 68-69:463-73. https://doi.org/10.1016/j.matbio.2017.12.012 PMid:29289644
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