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Recent Advances in Drug Delivery and Formulation

Editor-in-Chief

ISSN (Print): 2667-3878
ISSN (Online): 2667-3886

Research Article

Doxorubicin Loaded Gold Nanoparticles Mitigate Liver Fibrosis and Inflammatory Cytokines Gene Expression in Rat

Author(s): Yasmeen Ishaq, Hamna Naeem, Sana Khurshid*, Rabia Tabbasam and Zeeshan Haider

Volume 16, Issue 4, 2022

Published on: 28 October, 2022

Page: [309 - 316] Pages: 8

DOI: 10.2174/2667387817666221020090050

Price: $65

Abstract

Background: Gold nanoparticles have the potential to be used as a carrier in drug delivery systems due to their small size, large surface area and short circulation time in blood.

Objective: This study demonstrates that doxorubicin conjugation with gold nanoparticles (AuNPs) may reduce its toxicity as well as improve therapeutic efficacy.

Methods: Five groups of Albino rats were used; 1: healthy control, 2: injured, 3: injured and treated with Dox, 4: injured and treated with AuNPs, 5: injured and treated with AuNPs: Dox. At the end of the experiment, blood and liver tissues were processed for biochemical and histopathological analysis. The expression of collagen, HO-1, IL-6 and TNF-α genes involved in liver fibrosis was observed through real-time PCR.

Results: At the end of the experiment, it was observed that the body weights of DOX-treated rats decreased by 0.72%, however, AuNPs and Au: DOX-treated rats were 15.3% and 29.13% respectively. The percentage of liver protection determined through alanine aminotransferase and aspartate aminotransferase levels in DOX, AuNPs and AuNPs: DOX treated groups were 39.21%, 79.26%, 98.17% and 47.77%, 84.17%, 97.92%, respectively, representing better recovering liver in Dox-AuNPs treated rats compared to others. Histopathological and gene expression studies further support the findings. The mRNA expression levels of inflammatory and oxidative stress-related genes HO-1, IL-6 and TNF- α were upregulated in the injured group but downregulated in the treated group.

Conclusion: As depicted through biochemical, histopathological and gene expression studies, Au: DOX conjugate group seems to be protective against liver fibrosis.

Keywords: Heam oxygenase, collagen, drug delivery, liver fibrosis, gene expression, toxicity.

Graphical Abstract
[1]
Poilil Surendran S, George Thomas R, Moon MJ, Jeong YY. Nanoparticles for the treatment of liver fibrosis. Int J Nanomedicine 2017; 12: 6997-7006.
[http://dx.doi.org/10.2147/IJN.S145951] [PMID: 29033567]
[2]
EL Sayed HELSA. Morsy LELS, Abo Emara TM, Galhom RA. Effect of carbon tetrachloride (CCl4) on liver in adult albino rats: Histological study. Egypt J Hosp Med 2019; 76(6): 4254-61.
[http://dx.doi.org/10.21608/ejhm.2019.43804]
[3]
Dong S, Chen QL, Song YN, et al. Mechanisms of CCl<sub>4</sub>-induced liver fibrosis with combined transcriptomic and proteomic analysis. J Toxicol Sci 2016; 41(4): 561-72.
[http://dx.doi.org/10.2131/jts.41.561] [PMID: 27452039]
[4]
Mohajeri M, Sahebkar A. Protective effects of curcumin against doxorubicin-induced toxicity and resistance: A review. Crit Rev Oncol Hematol 2018; 122: 30-51.
[http://dx.doi.org/10.1016/j.critrevonc.2017.12.005] [PMID: 29458788]
[5]
Wang Q, Zhong Y, Liu W, et al. Enhanced chemotherapeutic efficacy of the low-dose doxorubicin in breast cancer via nanoparticle delivery system crosslinked hyaluronic acid. Drug Deliv 2019; 26(1): 12-22.
[http://dx.doi.org/10.1080/10717544.2018.1507057] [PMID: 30691317]
[6]
Abdelaziz HM, Gaber M, Abd-Elwakil MM, et al. Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates. J Control Release 2018; 269: 374-92.
[http://dx.doi.org/10.1016/j.jconrel.2017.11.036] [PMID: 29180168]
[7]
Bai X, Su G, Zhai S. Recent advances in nanomedicine for the diagnosis and therapy of liver fibrosis. Nanomaterials (Basel) 2020; 10(10): 1945.
[http://dx.doi.org/10.3390/nano10101945] [PMID: 33003520]
[8]
Li J, He X, Yang Y, Li M, Xu C, Yu R. Risk assessment of silica nanoparticles on liver injury in metabolic syndrome mice induced by fructose. Sci Total Environ 2018; 628-629: 366-74.
[PMID: 29448021]
[9]
Soule B, Tirucherai G, Kavita U, Kundu S, Christian R. Safety, tolerability, and pharmacokinetics of BMS-986263/ND-L02-s0201, a novel targeted lipid nanoparticle delivering HSP47 siRNA, in healthy participants: A randomised, placebo-controlled, double-blind, phase 1 study. J Hepatol 2018; 68: S112.
[10]
Małek A, Taciak B, Sobczak K, et al. Enhanced cytotoxic effect of doxorubicin conjugated to glutathione-stabilized gold nanoparticles in canine osteosarcoma-in vitro studies. Molecules 2021; 26(12): 3487.
[http://dx.doi.org/10.3390/molecules26123487] [PMID: 34201296]
[11]
Mohammad I. Gold nanoparticle: An efficient carrier for MCP I of Carica papaya seeds extract as an innovative male contraceptive in albino rats. J Drug Deliv Sci Technol 2019; 52: 942-56.
[http://dx.doi.org/10.1016/j.jddst.2019.06.010]
[12]
Vilas-Boas V, Vinken M. Hepatotoxicity induced by nanomaterials: Mechanisms and in vitro models. Arch Toxicol 2021; 95(1): 27-52.
[http://dx.doi.org/10.1007/s00204-020-02940-x] [PMID: 33155068]
[13]
Larbie C, Arthur FKN, Woode E, Terlabi EO. Evaluation of hepatoprotective effect of aqueous extract of Annona muricata (Linn.) leaf against carbon tetrachloride and acetaminophen-induced liver damage. J Nat Pharm 2012; 3(1): 25-5.
[http://dx.doi.org/10.4103/2229-5119.96957]
[14]
Zhao X, Zhang J, Tong N, Chen Y, Luo Y. Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice. Biol Pharm Bull 2012; 35(5): 796-800.
[http://dx.doi.org/10.1248/bpb.35.796] [PMID: 22687420]
[15]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001; 25(4): 402-8.
[16]
Wong MYW, Saad S, Wong MG, et al. Semicarbazide-sensitive amine oxidase inhibition ameliorates albuminuria and glomerulosclerosis but does not improve tubulointerstitial fibrosis in diabetic nephropathy. PLoS One 2020; 15(6): e0234617.
[http://dx.doi.org/10.1371/journal.pone.0234617] [PMID: 32555665]
[17]
Ribera J, Rodríguez-Vita J, Cordoba B, et al. Functionalized cerium oxide nanoparticles mitigate the oxidative stress and pro-inflammatory activity associated to the portal vein endothelium of cirrhotic rats. PLoS One 2019; 14(6): e0218716.
[http://dx.doi.org/10.1371/journal.pone.0218716] [PMID: 31233564]
[18]
Yu S, Liu F, Wang C, et al. Role of oxidative stress in liver toxicity induced by nickel oxide nanoparticles in rats. Mol Med Rep 2018; 17(2): 3133-9.
[PMID: 29257258]
[19]
Ullah H, Khan A, Baig MW, et al. Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice. BMC Complement Med Therap 2021; 20(1): 1-14.
[20]
Bae WK, Lee JH, Lee SJ, et al. Enhanced anti-cancer effect of 5-fluorouracil loaded into thermo-responsive conjugated linoleic acid-incorporated poloxamer hydrogel on metastatic colon cancer models. J Nanosci Nanotechnol 2011; 11(2): 1425-8.
[http://dx.doi.org/10.1166/jnn.2011.3403] [PMID: 21456204]
[21]
Aryal S, Grailer JJ, Pilla S, Steeber DA, Gong S. Doxorubicin conjugated gold nanoparticles as water-soluble and pH-responsive anticancer drug nanocarriers. J Mater Chem 2009; 19(42): 7879-84.
[http://dx.doi.org/10.1039/b914071a]
[22]
Abdalla WM, Hanan MS, El-Masry SA. Histopathological Effects of Doxorubicin and Nanoparticle Zinc oxide on DNA damage and Hepatotoxicity induced by CCl4 in rats. Egypt J Chem Environ Health 2017; 3(1): 59-73.
[23]
Wei Y, Huang M, Liu X, et al. Anti-fibrotic effect of plumbagin on CCl₄-lesioned rats. Cell Physiol Biochem 2015; 35(4): 1599-608.
[http://dx.doi.org/10.1159/000373974] [PMID: 25824458]
[24]
Gornicka A, Morris-Stiff G, Thapaliya S, Papouchado BG, Berk M, Feldstein AE. Transcriptional profile of genes involved in oxidative stress and antioxidant defense in a dietary murine model of steatohepatitis. Antioxid Redox Signal 2011; 15(2): 437-45.
[PMID: 21194384]

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