Alvin Julian, Niluh Suwasanti, Yudhiakuari Sincihu, Bernadette Dian Novita, Kevin Samsudin


Background: The widespread use of plastic and poor management of plastic waste is an environmental problem and has an impact on human health. The most commonly found microplastic contaminant is polyethylene polymer. Ingested microplastic particles will undergo an endocytosis mechanism and be absorbed into the bloodstream. This then triggers an increase in reactive oxygen species (ROS) which induces oxidative stress and results in an inflammatory response. This study tries to analyze the effect of administering microplastics on increasing blood serum C-reactive protein as a biomarker and marker of the inflammatory response due to microplastics.

Method: The experimental analytical research used 42 Rattus Norvegicus Wistar Strain animals, which were divided into 5 experimental groups and 1 control group. Quantitative data measurements/collection were carried out at two times (pre-post-test control group design) and analyzed by non-parametric comparison using the Friedman Test to see the increase in C-Reactive Protein (CRP) levels in the blood serum of Rattus norvegicus Wistar Strain before and after being given intake polyethylene microplastics.

Result: In all groups X0-X5, The results of the comparative test using the Friedman test showed a significant value of P = 0.000 (P < 0.05), so it can be concluded that there is a difference in pre and post experimental CRP levels.

Discussion: The increase in serum CRP levels from the control group to the X5 treatment group may be due to oxidative stress mechanisms, especially in hepatocyte cells, smooth muscle cells, macrophage cells, endothelial cells, lymphocyte cells and adipocyte cells which induce the production of CRP protein, especially native C-reactive protein (nCRP) and monomeric C-reactive protein (mCRP). The difference in serum CRP levels was significant (P = 0.000), where there was an increase in serum CRP levels post treatment (post experimental) from the lowest mean of 0.05 mg/L (pre experimental) to the highest of 0.98 mg/L on average, indicating that administration of microplastic intake at the dose studied had an impact on increasing serum CRP levels in response to an inflammatory reaction. The limitation of this research is that there are no journals that examine microplastics on serum CRP levels, resulting in a lack of research that can be used as a reference or comparative theory.

Conclusion: Administration of Microplastic Polyethylene at the dose studied in the treatment group caused a significant increase in Rattus Norvegicus Wistar Strain Serum CRP levels.

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Microplastic; Inflammatory Response; C-Reactive Protein

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Wright SL, Kelly FJ. Plastic and Human Health: A micro issue?. Environ Sci Technol. 2017;51(12):6634–47.

Jambeck JR, Geyer R, Wilcox C, Siegler TR, Perryman M, Andrady A, et al. Plastic waste inputs from land into the ocean. Science. 2015;347(6223):768–71.

Diaz-Basantes MF, Conesa JA, Fullana A. Microplastics in honey, beer, milk and refreshments in Ecuador as emerging contaminant. Sustainability. 2020;12(14):5514.

Lee H, Kunz A, Shim WJ, Walther BA. Microplastic contamination of table salts from Taiwan, including a global review. Sci Rep. 2019;9(1):10145.

Ribeiro F, Okoffo ED, O’Brien JW, Fraissinet-Tachet S, O’Brien S, Gallen M, et al. Quantitative analysis of selected plastics in high-commercial-value Australian seafood by pyrolysis gas chromatography mass spectrometry. Environ Sci Technol. 2020;54(15):9408–17.

Oliveri Conti G, Ferrante M, Banni M, Favara C, Nicolosi I, Cristaldi A, et al. Micro- and nano- plastics in edible fruit and vegetables. The first diet risks assessment for the general population. Environ Res. 2020;187:109677.

Cox KD, Covernton GA, Davies HL, Dower JF, Juanes F, Dudas SE. Human consumption of microplastics. Environ Sci Technol. 2019;53(12):7068–74.

Senathirajah K, Attwood S, Bhagwat G, Carbery M, Wilson S, Palanisami T. Estimation of the mass of microplastics ingested – A pivotal first step towards human health risk assessment. J Hazard Mater. 2021;404:124004.

Toussaint B, Raffael B, Angers-Loustau A, Gilliland D, Kestens V, Petrillo M, et al. Review of micro- and nanoplastic contamination in the food chain. Food Additives & Contaminants: Part A. 2019;36(5):639–73.

Rahman A, Sarkar A, Yadav OP, Achari G, Slobodnik J. Potential human health risks due to environmental exposure to nano- and microplastics and knowledge gaps: A scoping review. Science of The Total Environment. 2021;757:143872.

Prata JC, da Costa JP, Lopes I, Duarte AC, Rocha-Santos T. Environmental exposure to microplastics: An overview on possible human health effects. Science of The Total Environment. 2020;702:134455.

Pradhan S, Ghimire A, Bhattarai B, dkk. The role of C-reactive protein as a diagnostic predictor of sepsis in a multidisciplinary Intensive Care Unit of a tertiary care center in Nepal. Indian J Crit Care Med. 2016;20(7):417- 420. doi:10.4103/0972-5229.186226

Rhodes, B., Fürnrohr, B. G., & Vyse, T. J. C-reactive protein in rheumatology: biology and genetics. Nature Reviews Rheumatology. 2011;7(5), 282–289.

Anush MM, Ashok VK, Sarma RIN, Pillai SK. Role of c-reactive protein as an indicator for determining the outcome of sepsis. Indian J Crit Care Med. Published online 2019. doi:10.5005/jp-journals-10071-23105.

Nehring SM, Goyal A, Bansal P, Patel BC. C Reactive Protein. In: ; 2020

Devran Ö, Karakurt Z, Adigüzel N, dkk. C-reactive protein as a predictor of mortality in patients affected with severe sepsis in intensive care unit. Multidiscip Respir Med. 2012;7(6):1-6. doi:10.1186/2049-6958-7-47

Rochman, C. M. (2018). Microplastics research—from sink to source. Science, 360(6384), 28-29.

Browne, M. A., Crump, P., Niven, S. J., Teuten, E., Tonkin, A., & Galloway, T. S., et al. (2011). Accumulation of microplastic on shorelines worldwide: Sources and sinks. Environmental Science and Technology, 45, 9175–9179

Ciubotaru I, Potempa LA, Wander RC. Production of modified C-reactive protein U937-derived macrophages. Exp Biol Med (2005) 230(10):762–70. doi:10.1177/153537020523001010

Szalai AJ, van Ginkel FW, Dalrymple SA, Murray R, McGhee JR, Volankis JE. Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice. J Immunol (1998) 160(11):5294–9

Tillet WS, Francis T. Serological reactions in pneumonia with a nonprotein somatic fraction of Pneumococcus. J Exp Med (1930) 52(4):561–71. doi:10.1084/jem.52.4.561

Volanakis JE. Human C-reactive protein: expression structure and function. Mol Immunol (2001) 38:189–97. doi:10.1016/S0161-5890(01)00042-6

Black S, Kushner I, Samols D. C-reactive protein. J Biol Chem (2004) 279(47):48487–90. doi:10.1074/jbc.R400025200

Gewurz H, Mold C, Siegel J, Fiedel B. C-reactive protein and the acute phase response. Adv Intern Med (1982) 27:345–72.

Eisenhardt SU, Thiele JR, Bannasch H, Stark GB, Peter K. C-reactive protein: how conformational changes influence inflammatory properties. Cell Cycle (2009) 8(23):3885–92. doi:10.4161/cc.8.23.10068

Boncler M, Watala C. Regulation of cell function by isoforms of C-reactive protein: a comparative analysis. Acta Biochim Pol (2009) 56(1): 17–31.

Du Clos TW, Mold C. C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res (2004) 30(3):261–77. doi:10.1385/IR:30:3:261

Potempa LA, Siegel JN, Fedel BA, Potempa RT, Gewurz H. Expression, detection and assay of a neoantigen (Neo-CRP) associated with a free, human C-reactive protein subunit. Mol Immunol (1987) 24(5):531–41. doi:10.1016/ 0161-5890(87)90028-9

Potempa LA, Maldonado BA, Laurent P, Zemel ES, Gewurz H. Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Mol Immunol (1983) 20(11):1165–75. doi:10.1016/0161-5890(83)90140-2

Devaraj S, Venugopal S, Jialal I. Native pentameric C-reactive protein displays more potent pro-atherogenic activities in human aortic endothelial cells than modified C-reactive protein. Atherosclerosis (2006) 184:48–52. doi:10.1016/j.atherosclerosis.2005.03.031

Hage FG, Szalai AJ. C-reactive protein gene polymorphisms, C-reactive protein blood levels and cardiovascular disease risk. J Am Coll Cardiol (2007) 50(12):1115–22. doi:10.1016/j.jacc.2007.06.012

Weinhold B, Bader A, Valeria POLI, Rütehr U. Interleukin-6 is necessary, but not sufficient, for induction of the human C-reactive protein gene in vivo. Biochem J (1997) 325(3):617–21. doi:10.1042/bj3250617

Sproston, N. R., & Ashworth, J. J. Role of C-reactive protein at sites of inflammation and infection. Frontiers in immunology (2018)., 9, 754.

Thiele JR, Habersberger J, Braig D, Schmidt Y, Goerendt K, Maurer V, et al. Dissociation of pentameric to monomeric C-reactive protein localises and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy. Circulation (2014) 130: 35–50. doi:10.1161/CIRCULATIONAHA.113.007124

Du Clos TW. Pentraxins: structure, function and role in inflammation. ISRN Inflamm (2013) 2013:379040. doi:10.1155/2013/379040

Ji SR, Wu J, Zhu L, Potempa LA, Sheng FL, Lu W, et al. Cell membranes and liposomes dissociate C-reactive protein (CRP) to form new, biologically active structural intermediate: mCRPm. FASEB J (2007) 21:284–94. doi:10.1096/fj.06-6722com

Boras E, Slevin M, Alexander MY, Aljohi A, Gilmore W, Ashworth J, et al. Monomeric C-reactive protein and Notch-3 co-operatively increase angiogenesis through PI3K signalling pathway. Cytokine (2014) 69:165–79. doi:10.1016/j.cyto.2014.05.027

Macintyre S, Samols D, Dailey P. Two carboxylesterases bind C-reactive protein within the endoplasmic reticulum and regulate its secretion during the acute phase response. J Biol Chem (1994) 269(39):24496–503.

Zhang D, Sun M, Samols D, Kushner I. STAT3 participates in transcriptional activation of the C-reactive protein gene by interleukin-6. J Biol Chem (1996) 271(16):9503–9. doi:10.1074/jbc.271.16.9503

Clyne B, Olshaker JS. The C-reactive protein. J Emerg Med (1999) 17(6):1019–25. doi:10.1016/S0736-4679(99)00135-3

Albu E, Miller BM, Choi Y, Lakhanpal S, Murthy RN, Gerst PH. Diagnostic value of C-reactive protein in acute appendicitis. Dis Colon Rectum (1994) 37(1):49–51. doi:10.1007/BF02047214

Juvonen T, Kiviniemi H, Niemelä O, Kairaluoma MI. Diagnositic accuracy of ultrasonography and C reactive protein concentration in acute cholecystitis: a prospective clinical study. Eur J Surg (1991) 158(6–7):365–9.

Wilson C, Heads A, Shenkin A, Imrie CW. C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis. Br J Surg (1989) 76(2):177–81. doi:10.1002/bjs.1800760224

Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med (1999) 340(6):448–54. doi:10.1056/ NEJM199902113400607

Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure (1999) 7(2):169–77. doi:10.1016/S0969-2126(99)80023-9

Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation (2003) 107:363–9. doi:10.1161/01. CIR.0000053730.47739.3C

Weinhold B, Bader A, Valeria POLI, Rütehr U. Interleukin-6 is necessary, but not sufficient, for induction of the human C-reactive protein gene in vivo. Biochem J (1997) 325(3):617–21. doi:10.1042/bj3250617

Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Investig (2003) 111(12):1805–12. doi:10.1172/JCI200318921

Kurtz EG, Ridker PM, Rose LM, Cook NR, Everett BM, Buring JE, et al. Oral postmenopausal hormone therapy, C-reactive protein and cardiovascular outcomes. Menopause (2011) 18(1):23–9. doi:10.1097/gme.0b013e3181e750dd

Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation (1999) 100(7):713–6. doi:10.1161/01.CIR.100.3.230

Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med (2000) 342(12):836–43. doi:10.1056/NEJM200003233421202

Decensi A, Omodei U, Robertson C, Bonanni B, Guerrieri-Gonzaga A, Ramazzotto F. et al. Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women. Circulation (2002) 106(10):1224–8. doi:10.1161/01.CIR.0000028463. 74880.EA

Vongpatanasin W, Tuncel M, Wang Z, Arbique D, Mehrad B, Jialal I. Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women. J Am Coll Cardiol (2003) 41(8):1358–63. doi:10.1016/S0735-1097(03)00156-6

Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med (2002) 347(20):1557–65. doi:10.1056/ NEJMoa021993

Osman R, L’Allier PL, Elgharib N, Tardif JC. Critical appraisal of C-reactive protein throughout the spectrum of cardiovascular disease. Vasc Health Risk Manag (2006) 2(3):221. doi:10.2147/vhrm.2006.2.3.221

Kushner I. C-reactive protein and the acute-phase response. Hosp Pract (Off Ed) (1990) 25(3A):13–6.

Soinio M, Marniemi J, Laakso M, Lehto S, Rönnemaa TT. High sensitivity C-reactive protein and coronary heart disease mortality in type 2 diabetic patients – a 7 year follow up study. Diabetes Care (2006) 29(2):329–33. doi:10.2337/diacare.29.02.06.dc05-1700

Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, et al. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature (2006) 440:1217–21. doi:10.1038/nature04672

Slevin M, Matou S, Zeinolabediny Y, Corpas R, Weston R, Liu D, et al. Monomeric C-reactive protein – a key molecule driving development of Alzheimer’s disease associated with brain ischaemia? Sci Rep (2015) 5:13281. doi:10.1038/srep13281

Verma S, Szmitko PE, Yeh ET. C-reactive protein: structure affects function. Circulation (2004) 109:1914–7.doi:10.1161/01.CIR.0000127085.32999.64

Gao, D., Liu, X., Junaid, M., Liao, H., Chen, G., Wu, Y., & Wang, J. (2022). Toxicological impacts of micro (nano) plastics in the benthic environment. Science of The Total Environment, 836, 155620.

Lian, Y., Liu, W., Shi, R., Zeb, A., Wang, Q., Li, J., ... & Tang, J. (2022). Effects of polyethylene and polylactic acid microplastics on plant growth and bacterial community in the soil. Journal of Hazardous Materials, 435, 129057.

Wu, P., Lin, S., Cao, G., Wu, J., Jin, H., Wang, C., ... & Cai, Z. (2022). Absorption, distribution, metabolism, excretion and toxicity of microplastics in the human body and health implications. Journal of Hazardous Materials, 437, 129361.

Pellegrini, C., Saliu, F., Bosman, A., Sammartino, I., Raguso, C., Mercorella, A., ... & Rovere, M. Hotspots of microplastic accumulation at the land-sea transition and their spatial heterogeneity: The Po River prodelta (Adriatic Sea). Science of The Total Environment, (2023). 895, 164908.

Das, A. The emerging role of microplastics in systemic toxicity: Involvement of reactive oxygen species (ROS). Science of The Total Environment, (2023). 165076.

Ali, I., Cheng, Q., Ding, T., Yiguang, Q., Yuechao, Z., Sun, H., ... & Liu, J. (2021). Micro-and nanoplastics in the environment: Occurrence, detection, characterization and toxicity–A critical review. Journal of Cleaner Production, 313, 127863.

Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. J Am Med Assoc (2001) 286(3):327–34. doi:10.1001/jama.286.3.327

Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, inetleukin-6 and tumour necrosis factor-α. Mol Psychiatry (2016) 21:642–9. doi:10.1038/mp.2015.67

Tanaka T, Kishimoto T. The biology and medical implications of interleukin-6. Cancer Immunol Res (2014) 2(4):288–94. doi:10.1158/2326-6066. CIR-14-0022

Du Clos TW. Function of C-reactive protein. Ann Med (2000) 32(4):274–8. doi:10.3109/07853890009011772

Braig D, Nero TL, Koch HG, Kaiser B, Wang X, Thiele JR, et al. Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites. Nat Commun (2017) 8:14188. doi:10.1038/ncomms14188

Kaplan MH, Volanakis JE. Interaction of C-reactive protein complexes with the complement system I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol (1974) 112(6):2135–47.

Torzewski J, Torzewski M, Bowyer DE, Fröhlich M, Koenig W, Waltenberger J, et al. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler Thromb Vasc Biol (1998) 18(9):1386–92. doi:10.1161/01. ATV.18.9.1386

Lagrand WK, Niessen HW, Wolbink GJ, Jaspars LH, Visser CA, Verheugt FW, et al. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation (1997) 95(1):97–103. doi:10.1161/01.CIR.95.1.97

Gitlin JD, Gitlin JI, Gitlin D. Localizing of C-reactive protein in synovium of patients with rheumatoid arthritis. Arthritis Rheum (1977) 20(8):1491–9. doi:10.1002/art.1780200808

Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest (1993) 91:1351–7. doi:10.1172/JCI116336

Krayem I, Bazzi S, Karam M. The combination of CRP isoforms with oxLDL decreases TNF-α and IL-6 release by U937-derived macrophages. Biomed Rep (2017) 7:272–6. doi:10.3892/br.2017.949 101. Koch AE, Polverini PJ, Kunkel SL, Harlow LA, D

Yao Z, Seong HJ, Jang YS. Environmental toxicity and decomposition of polyethylene. Ecotoxicol Environ Saf [Internet] 2022 [cited 2023 Oct 27];242:113933. Available from:

BT Laboratory. Mouse C-Reactive Protein, CRP ELISA Kit. 2022 [cited 2023 Sept 27];242:113933. Available from:

Campanale, Massarelli, Savino, Locaputo, Uricchio. A detailed review study on potential effects of microplastics and additives of concern on human health. Int J Environ Res Public Health [Internet] 2020 [cited 2023 Dec 29];17(4):1212. Available from:

Sincihu Y, Lusno MFD, Mulyasari TM, Elias SM, Sudiana IK, Kusumastuti K, et al. Wistar rats hippocampal neurons response to blood low-density polyethylene microplastics: a pathway analysis of SOD, CAT, MDA, 8- OHdG expression in hippocampal neurons and blood serum Aβ42 levels. Neuropsychiatr Dis Treat 2023;Volume 19:73–83

Wright SL, Kelly FJ. Plastic and Human Health: A Micro Issue? Environ Sci Technol [Internet] 2017 [cited 2024 Jan 13];51(12):6634–47. Available from:

Ranneh Y, Ali F, Akim AM, Hamid HAbd, Khazaai H, Fadel A. Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: a review. Appl Biol Chem [Internet] 2017 [cited 2023 Jan 7];60(3):327–38. Available from: 9#citeas

Aranda-Rivera AK, Cruz-Gregorio A, Arancibia-Hernández YL, Hernández-Cruz EY, Pedraza-Chaverri J. RONS and oxidative stress: an overview of basic concepts. Oxygen [Internet] 2022 [cited 2023 Jan 6];2(4):437–78. Available from:

Ghosh N, Das A, Chaffee S, Roy S, Sen CK. Reactive oxygen Species, oxidative damage and cell death [Internet]. In: Immunity and Inflammation in Health and Disease. Elsevier; 2018 [cited 2023 Mar6].page45–55Available from:

Shields HJ, Traa A, Van Raamsdonk JM. Beneficial and detrimental effects of reactive oxygen species on lifespan: a comprehensive review of comparative and experimental studies. Front Cell Dev Biol [Internet] 2021 [cited 2023 Mar 6];9. Available from:

Deng Y, Zhang Y, Lemos B, Ren H. Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure. 2017 [cited 2023 Dec 29];7(46687). Available from:

Gabay, C., & Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. New England journal of medicine, 340(6), 448-454.



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