Silver nanoparticles modulate high fat high carbohydrate diet induced metabolic changes in rats via reducing lipid peroxidation, PDGF-β and insulin resistance

Document Type : Research Paper

Authors

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura Egypt

Abstract

Objective(s): Non-alcoholic fatty liver disease (NAFLD) is strongly linked with insulin resistance and type-2 diabetes through various metabolic changes. The current study was designed to investigate the modulatory effects of silver nanoparticles (AgNPs) on metabolic and inflammatory changes activated during NAFLD. 
Materials and Methods: Three doses of AgNPs (100, 150, and 200 μg/kg/day for 4 weeks) were tested in a high-fat high carbohydrate diet (HFHCD) induced NAFLD model in rats. 
Results: Sinificant (P<0.05) improvement in dyslipidemia, hyperglycemia, and insulin levels by AgNPs was observed and more notably in the group that received 200 μg/kg/day AgNPs. Acute phase inflammatory protein C-reactive protein and monocytes chemoattractant protein-1 were significantly (P<0.05) lowered by AgNPs. Inline, lipid peroxidation and PDGF-β levels were significantly (P<0.05) reduced in groups that received different doses of AgNPs. Furthermore, AgNPs especially in the large dose (200 μg/kg/day) significantly decreased (P<0.05) the measured level of the inflammatory cytokines (IL-1β, IL-6, and TNF-α) compared with the HFHCD group level.
Conclusion: Collectively, results propose the ability of AgNPs to modulate metabolic changes accompa-nying NAFLD through reducing lipid peroxidation and targeting inflammatory cytokines mediating insulin resistance.

Keywords


Olefsky JM, Nolan JJ. Insulin resistance and non-insulin-dependent diabetes mellitus: cellular and molecular mechanisms. Am J Clin Nutr. 1995;61(4):980S-986S.
Kahn SE, The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 2003;46(1):3-19.
Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, Tsukumo DM, Anhe G, Amaral ME, Takahashi HK, Curi R. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci 2009;29(2):359-370.
Dunn W, Schwimmer JB. The obesity epidemic and nonalcoholic fatty liver disease in children. Curr Gastroenterol Rep 2008;10(1):67-72.
Perry RJ, Zhang D, Zhang XM, Boyer JL, Shulman GI. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science. 2015;347(6227):1253-1256.
Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK. Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations. Beilstein J Nanotechnol 2018;9(1):1050-1074.
Khuroo T, Atifa U, Iqbal Z. Oral Formulation of Paclitaxel and Erlotinib Polymeric Nanoparticles: A Potential Combination to Treat Breast Cancer. Biomed J Sci Technol Res 2020;31(4):24338-24340.
Anzar N, Mirza MA, Anwer K, Khuroo T, Alshetaili AS, Alshahrani SM, Meena J, Hasan N, Talegaonkar S, Panda AK, Iqbal Z. Preparation, evaluation and pharmacokinetic studies of spray dried PLGA polymeric submicron particles of simvastatin for the effective treatment of breast cancer. J Mol Liq 2018;249:609-16.
Padhi S, Mirza MA, Verma D, Khuroo T, Panda AK, Talegaonkar S, Khar RK, Iqbal Z. Revisiting the nanoformulation design approach for effective delivery of topotecan in its stable form: An appraisal of its in vitro Behavior and tumor amelioration potential. Drug Deliv 2016;23(8):2827-2837.
Shaheen TI, El-Naggar ME, Hussein JS, El-Bana M, Emara E, El-Khayat Z, Fouda MM, Ebaid H, Hebeish A. Antidiabetic assessment; in vivo study of gold and core-shell silver-gold nanoparticles on streptozotocin-induced diabetic rats. Biomed Pharmacother 2016;83:865-875.
Sengottaiyan A, Aravinthan A, Sudhakar C, Selvam K, Srinivasan P, Govarthanan M, Manoharan K, Selvankumar T. Synthesis and characterization of Solanum nigrum-mediated silver nanoparticles and its protective effect on alloxan-induced diabetic rats. J Nanostructure Chem 2016; 6(1):41-48.
Sung JH, Ji JH, Park JD, Yoon JU, Kim DS, Jeon KS, Song MY, Jeong J, Han BS, Han JH, Chung YH. Subchronic inhalation toxicity of silver nanoparticles. Toxicol Sci 2009;108(2):452-461.Williams K, Milner J, Boudreau MD, Gokulan K, Cerniglia CE, Khare S. Effects of subchronic exposure of silver nanoparticles on intestinal microbiota and gut-associated immune responses in the ileum of Sprague-Dawley rats. Nanotoxicology 2015;9(3):279-789.
Mittal AK, Bhaumik J, Kumar S, Banerjee UC. Biosynthesis of silver nanoparticles: elucidation of prospective mechanism and therapeutic potential. J Colloid Interface Sci 2014;415:39-47.
Dziendzikowska K, Gromadzka‐Ostrowska J, Lankoff A, Oczkowski M, Krawczyńska A, Chwastowska J, Sadowska‐Bratek M, Chajduk E, Wojewodzka M, Dušinská M, Kruszewski M. Time‐dependent biodistribution and excretion of silver nanoparticles in male Wistar rats. J Appl Toxicol 2012;32(11):920-928.
Begum SR, Rao DM, Reddy PD. Role of Green Route Synthesized Silver Nanoparticles in Medicinal Applications with Special Reference to Cancer Therapy. Biosci Biotechnol Res Asia 2018; 15(4):783-790.
Franci G, Falanga A, Galdiero S, Palomba L, Rai M, Morelli G, Galdiero M. Silver nanoparticles as potential antibacterial agents. Molecules 2015; 20(5):8856-8874.
Krajewska JB, Długosz O, Sałaga M, Banach M, Fichna J. Silver nanoparticles based on blackcurrant extract show potent anti-inflammatory effect in vitro and in DSS-induced colitis in mice. Int J Pharm 2020;585:119549.
Jini D, Sharmila S. Green synthesis of silver nanoparticles from Allium cepa and its in vitro antidiabetic activity. Mater. Today: Proc. 2020;22:432-438.
Popli D, Anil V, Subramanyam AB, MN N, VR R, Rao SN, Rai RV, Govindappa M. Endophyte fungi, Cladosporium species-mediated synthesis of silver nanoparticles possessing in vitro antioxidant, anti-diabetic and anti-Alzheimer activity. Artif Cells Nanomed Biotech 2018;46:676-683. 
Birudu RB, Naik MJ, Janardhan M. Ethanolic extract of Passiflora foetida and silver nanoparticles on carbohydrate metabolic enzymes of dextrose induced diabetic rats. J Biochem Biopharm Biomed Sci 2015;1(1):12-19.
Mosa WF, El-Shehawi AM, Mackled MI, Salem MZ, Ghareeb RY, Hafez EE, Behiry SI, Abdelsalam NR. Productivity performance of peach trees, insecticidal and antibacterial bioactivities of leaf extracts as affected by nanofertilizers foliar application. Sci Rep 2021;11(1):1-9.
Abu-Elsaad N, El-Karef A. Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1alpha by luteolin. Pharmacol Rep 2019;71(4): 688-694.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351-358.
Fang YL, Chen H, Wang CL, Liang L. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”. World J Gastroenterol 2018;24(27):2974.
Te Sligte K, Bourass I, Sels JP, Driessen A, Stockbrűgger RW, Koek GH. Non-alcoholic steatohepatitis: review of a growing medical problem. Eur J Intern Med 2004;15(1): 10-21
Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004;24(5):816-823.
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414(6865):813-820.
Rai VK, Mishra N, Agrawal AK, Jain S, Yadav NP. Novel drug delivery system: an immense hope for diabetics. Drug Deliv 2016;23(7):2371-2390
Soenen SJ, Rivera-Gil P, Montenegro JM, Parak WJ, De Smedt SC, Braeckmans K. Cellular toxicity of inorganic nanoparticles: common aspects and guidelines for improved nanotoxicity evaluation. Nano today 2011;6(5):446-465.
Annu M, Ahmed S, Kaur G, Sharma P, Singh S, Ikram S. Evaluation of the antioxidant, antibacterial and anticancer (lung cancer cell line A549) activity of Punica granatum mediated silver nanoparticles. Toxicology research. 2018 Sep 1;7(5):923-30.
Vazquez-Muñoz R, Borrego B, Juárez-Moreno K, García-García M, Morales JD, Bogdanchikova N, Huerta-Saquero A. Toxicity of silver nanoparticles in biological systems: does the complexity of biological systems matter? Toxicol Lett 2017;276:11-20.
Cho YM, Mizuta Y, Akagi JI, Toyoda T, Sone M, Ogawa K. Size-dependent acute toxicity of silver nanoparticles in mice. Journal of toxicologic pathology. 2018;31(1):73-80.
Kim TH, Kim M, Park HS, Shin US, Gong MS, Kim HW. Size‐dependent cellular toxicity of silver nanoparticles. J Biomed Mater Res A 2012;100(4):1033-1043.
Krutyakov YA, Kudrinskiy AA, Olenin AY, Lisichkin GV. Synthesis and properties of silver nanoparticles: advances and prospects. Russ Chem Rev 2008;77(3):233.
Guo JZ, Cui H, Zhou W, Wang W. Ag nanoparticle-catalyzed chemiluminescent reaction between luminol and hydrogen peroxide. J Photochem Photobiol A 2008;193(2-3):89-96
Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complicat 2005;19(3):178-181
Hirsch IB. Intensifying insulin therapy in patients with type 2 diabetes mellitus. Am J Med 2005;118(5):21-26
Jones SC, Saunders HJ, Qi W, Pollock CA. Intermittent high glucose enhances cell growth and collagen synthesis in cultured human tubulointerstitial cells. Diabetologia 1999;42(9):1113-1119
Shomali M. Diabetes treatment in 2025: can scientific advances keep pace with prevalence? Ther Adv Endocrinol 2012;3(5):163-173
Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig 2017;114(12):1752-1761
Simoneau JA, Veerkamp JH, Turcotte LP, Kelley DE. Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEB J 1999;13(14):2051-2060
Lee HM, Kim JJ, Kim HJ, Shong M, Ku BJ, Jo EK. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes. 2013;62(1):194-204
Meng XF, Wang XL, Tian XJ, Yang ZH, Chu GP, Zhang J, Li M, Shi J, Zhang C. Nod-like receptor protein 1 inflammasome mediates neuron injury under high glucose. Mol Neurobiol 2014;49(2):673-684
Koenen TB, Stienstra R, Van Tits LJ, De Graaf J, Stalenhoef AF, Joosten LA, Tack CJ, Netea MG. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1β transcription in human adipose tissue. Diabetes. 2011;60(2):517-524
Serbina NV, Jia T, Hohl TM, Pamer EG. Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 2008;26:421-452
Weber C, Belge KU, Von Hundelshausen P, Draude G, Steppich B, Mack M, Frankenberger M, Weber KS, Ziegler‐Heitbrock HW. Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 2000;67(5):699-704
Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 2004;279(31):32345-32353
Zhang XQ, Xu CF, Yu CH, Chen WX, Li YM. Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease. WJG 2014;20(7):1768
Gross B, Pawlak M, Lefebvre P, Staels B. PPARs in obesity induced T2DM, dyslipidaemia and NAFLD. Nat Rev Endocrinol 2017;13(1):36-49
McGarry JD. What if Minkowski had been ageusic? An alternative angle on diabetes. Science 1992;258(5083):766-770
Sharma M, Vikram NK, Misra A, Bhatt S, Tarique M, Parray HA, Pandey RM, Luthra K. Assessment of 11-β hydroxysteroid dehydrogenase (11-βHSD1) 4478T> G and tumor necrosis factor-α (TNF-α)-308G> A polymorphisms with obesity and insulin resistance in Asian Indians in North India. Mol Biol Rep 2013;40(11):6261-6270
Fernandez-Veledo S, Vila-Bedmar R, Nieto-Vazquez I, Lorenzo M. c-Jun N-terminal kinase 1/2 activation by tumor necrosis factor-α induces insulin resistance in human visceral but not subcutaneous adipocytes: reversal by liver X receptor agonists. J Clin Endocrinol Metab 2009;94(9):3583-3593
Han D, Hanawa N, Saberi B, Kaplowitz N. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. Am. J. Physiol. Gastrointest. Liver Physiol 2006;291(1):G1-G7
Han D, Hanawa N, Saberi B, Kaplowitz N. Hydrogen peroxide and redox modulation sensitize primary mouse hepatocytes to TNF-induced apoptosis. Free Radic Biol Med 2006;41(4):627-639
Dou L, Zhao T, Wang L, Huang X, Jiao J, Gao D, Zhang H, Shen T, Man Y, Wang S, Li J. miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes. J Biol Chem 2013;288(31):22596-22606
Castañeda S, Remuzgo-Martínez S, López-Mejías R, Genre F, Calvo-Alén J, Llorente I, Aurrecoechea E, Ortiz AM, Triguero A, Blanco R, Llorca J. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis. Clin Exp Rheumatol 2019;37(3):465473.
Akbari M, Hassan-Zadeh V. IL-6 signalling pathways and the development of type 2 diabetes. Inflammopharmacology 2018;26(3):685-698.
Ji C, Chen X, Gao C, Jiao L, Wang J, Xu G, Fu H, Guo X, Zhao Y. IL-6 induces lipolysis and mitochondrial dysfunction but does not affect insulin-mediated glucose transport in 3T3-L1 adipocytes. J Bioenerg Biomembr 2011;43(4):367.