Modulatory Effects of Fucoidan on Paracetamol-induced Hepatic Damage and Histological Alterations in Rasbora lateristriata
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Abstract
Paracetamol overdose is a well-documented cause of hepatic injury across vertebrate species, including teleost fish. This study aimed to evaluate the hepatoprotective potential of fucoidan, a sulfated polysaccharide derived from brown algae, against paracetamol-induced liver damage in Rasbora lateristriata. Fish were divided into five experimental groups and exposed to paracetamol (3 mg/L), either alone or in combination with fucoidan at concentrations of 50, 100, or 300 µg/mL, for seven days. Histopathological evaluation of liver tissues was performed using hematoxylin–eosin staining, with semi-quantitative scoring focused on hydropic degeneration, nuclear pyknosis, and necrosis. The results demonstrated that paracetamol exposure induced moderate hepatocellular injury, characterized by cytoplasmic vacuolization, apoptotic nuclear alterations, and necrotic lesions. Co-treatment with fucoidan at 300 µg/mL was associated with reduced severity across all histopathological parameters, indicating partial hepatoprotective effects. In contrast, the 50 µg/mL fucoidan group exhibited paradoxically severe hydropic degeneration despite the absence of pyknosis and necrosis, suggesting a delayed or altered injury profile. Intermediate outcomes were observed at 100 µg/mL. Overall, fucoidan exhibited dose-dependent but inconsistent hepatoprotective effects. The observed histological variability across concentrations suggests that protection may be influenced by factors such as bioavailability, cellular uptake, or interactions with intracellular stress pathways. These findings highlight the need for further mechanistic investigations before fucoidan can be considered a reliable hepatoprotective agent in aquatic toxicology.
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References
A. I. A. Dewanti et al., “Effects of Paracetamol on the Development of Zebrafish (Danio rerio),” JTAS, vol. 46, no. 4, pp. 1173–1188, Oct. 2023, doi: 10.47836/pjtas.46.4.06.
S. S. Ayoub, “Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action,” Temperature, vol. 8, no. 4, pp. 351–371, Oct. 2021, doi: 10.1080/23328940.2021.1886392.
G. G. Graham, M. J. Davies, R. O. Day, A. Mohamudally, and K. F. Scott, “The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings,” Inflammopharmacol, vol. 21, no. 3, pp. 201–232, Jun. 2013, doi: 10.1007/s10787-013-0172-x.
N. I. Septriani et al., “Histopathological evaluation of hepatic tissue of yellow Rasbora (Rasbora lateristriata) exposed to paracetamol,” Biological. Environ. Pollut., vol. 3, no. 1, pp. 8–14, Jun. 2023, doi: 10.31763/bioenvipo.v3i1.595.
U. Freo, C. Ruocco, A. Valerio, I. Scagnol, and E. Nisoli, “Paracetamol: A Review of Guideline Recommendations,” Journal of Clinical Medicine, vol. 10, no. 15, p. 3420, Jul. 2021, doi: 10.3390/jcm10153420.
J. G. M. Bessems and N. P. E. Vermeulen, “Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches,” Critical Reviews in Toxicology, vol. 31, no. 1, pp. 55–138, Jan. 2001, doi: 10.1080/20014091111677.
A. S. Chidiac, N. A. Buckley, F. Noghrehchi, and R. Cairns, “Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease,” Expert Opinion on Drug Metabolism & Toxicology, vol. 19, no. 5, pp. 297–317, May 2023, doi: 10.1080/17425255.2023.2223959.
L. F. Prescott, “Paracetamol (acetaminophen) poisoning: The early years,” Brit J Clinical Pharma, vol. 90, no. 1, pp. 127–134, Jan. 2024, doi: 10.1111/bcp.15903.
W. Ariesti et al., “Histopathological Effects of Mangosteen (Garcinia mangostana L.) Peel Decoction on Betta Fish (Betta sp.) Liver,” Biota, vol. 17, no. 2, pp. 58–70, 2024, doi: 10.20414/jb.v17i2.508.
G. N. Matus, B. V. R. Pereira, E. C. M. Silva-Zacarin, M. J. Costa, A. Cordeiro Alves Dos Santos, and B. Nunes, “Behavior and histopathology as biomarkers for evaluation of the effects of paracetamol and propranolol in the neotropical fish species Phalloceros harpagos,” Environmental Science and Pollution Research, vol. 25, no. 28, pp. 28601–28618, Oct. 2018, doi: 10.1007/s11356-018-2839-8.
O. Mayani et al., “Embryotoxic and Teratogenic Effects of Monosodium Glutamate and Saccharin on Wader (Rasbora lateristriata) Fish,” Suranaree J Sci Technol, vol. 31, no. 6, p. 030243(1–9), Feb. 2025, doi: 10.55766/sujst-2024-06-e04047.
B. Retnoaji et al., “Embryonic development of Indonesian native fish yellow rasbora (Rasbora lateristriata),” Journal of King Saud University - Science, vol. 35, no. 7, p. 102810, Oct. 2023, doi: 10.1016/j.jksus.2023.102810.
L. U. Khasanah, P. Paramita, and B. Retnoaji, “Mangosteen (Garcinia mangostana L.) Peel Decoction Effect on Embryological Development of Wader Pari Fish Rasbora lateristriata (Bleeker, 1854),” J.Tropical Biodiversity Biotechnology, vol. 9, no. 2, p. 80645, Apr. 2024, doi: 10.22146/jtbb.80645.
Q. Zhong et al., “The Antioxidant Activity of Polysaccharides Derived from Marine Organisms: An Overview,” Marine Drugs, vol. 17, no. 12, p. 674, Nov. 2019, doi: 10.3390/md17120674.
D. G. Nair, R. Weiskirchen, and S. K. Al-Musharafi, “The use of marine-derived bioactive compounds as potential hepatoprotective agents,” Acta Pharmacol Sin, vol. 36, no. 2, pp. 158–170, Feb. 2015, doi: 10.1038/aps.2014.114.
J. H. Fitton, “Therapies from Fucoidan; Multifunctional Marine Polymers,” Marine Drugs, vol. 9, no. 10, pp. 1731–1760, Sep. 2011, doi: 10.3390/md9101731.
J. Li, C. Guo, and J. Wu, “Fucoidan: Biological Activity in Liver Diseases,” Am. J. Chin. Med., vol. 48, no. 07, pp. 1617–1632, Jan. 2020, doi: 10.1142/S0192415X20500809.
M. T. Ale, J. D. Mikkelsen, and A. S. Meyer, “Important Determinants for Fucoidan Bioactivity: A Critical Review of Structure-Function Relations and Extraction Methods for Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds,” Marine Drugs, vol. 9, no. 10, pp. 2106–2130, Oct. 2011, doi: 10.3390/md9102106.
I. Cheng, S. Weng, M. Wu, F. Suk, G. Lien, and C. Chen, “Low‐molecular‐weight fucoidan and high‐stability fucoxanthin decrease serum alanine transaminase in patients with nonalcoholic fatty liver disease—A double‐blind, randomized controlled trial,” Adv in Digestive Med, vol. 6, no. 3, pp. 116–122, Sep. 2019, doi: 10.1002/aid2.13125.
L. Yang et al., “Fucoidan Derived from Undaria pinnatifida Induces Apoptosis in Human Hepatocellular Carcinoma SMMC-7721 Cells via the ROS-Mediated Mitochondrial Pathway,” Marine Drugs, vol. 11, no. 6, pp. 1961–1976, Jun. 2013, doi: 10.3390/md11061961.
W. Ikeda-Ohtsubo et al., “Intestinal Microbiota and Immune Modulation in Zebrafish by Fucoidan From Okinawa Mozuku (Cladosiphon okamuranus),” Front. Nutr., vol. 7, p. 67, Jun. 2020, doi: 10.3389/fnut.2020.00067.
J.-W. Jeong et al., “Fucoidan inhibits lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and zebrafish larvae,” Mol. Cell. Toxicol., vol. 13, no. 4, pp. 405–417, Dec. 2017, doi: 10.1007/s13273-017-0045-2.
S.-H. Lee et al., “Anti-inflammatory effect of fucoidan extracted from Ecklonia cava in zebrafish model,” Carbohydrate Polymers, vol. 92, no. 1, pp. 84–89, Jan. 2013, doi: 10.1016/j.carbpol.2012.09.066.
V. P. Cedron, A. M. J. Weiner, M. Vera, and L. Sanchez, “Acetaminophen affects the survivor, pigmentation and development of craniofacial structures in zebrafish (Danio rerio) embryos,” Biochemical Pharmacology, vol. 174, p. 113816, Apr. 2020, doi: 10.1016/j.bcp.2020.113816.
N. I. Septriani et al., “Pengaruh Fucoidan Terhadap Struktur Hepar Ikan Zebra (Danio rerio, Hamilton 1822) yang Diberi Parasetamol Dosis Tinggi,” Al-Kauniyah J. Biol., vol. 17, no. 2, pp. 257–267, May 2024, doi: 10.15408/kauniyah.v17i2.27185.
K. N. Gibson-Corley, A. K. Olivier, and D. K. Meyerholz, “Principles for Valid Histopathologic Scoring in Research,” Veterinary Pathology, vol. 50, no. 6, pp. 1007–1015, Nov. 2013, doi: 10.1177/0300985813485099.
I. C. Guiloski et al., “Paracetamol causes endocrine disruption and hepatotoxicity in male fish Rhamdia quelen after subchronic exposure,” Environmental Toxicology and Pharmacology, vol. 53, pp. 111–120, Jul. 2017, doi: 10.1016/j.etap.2017.05.005.
G. A. Elizalde-Velázquez et al., “Low concentrations of ciprofloxacin alone and in combination with paracetamol induce oxidative stress, upregulation of apoptotic-related genes, histological alterations in the liver, and genotoxicity in Danio rerio,” Chemosphere, vol. 294, p. 133667, May 2022, doi: 10.1016/j.chemosphere.2022.133667.
A. A. E. Latif et al., “Protective role of Chlorella vulgaris with Thiamine against Paracetamol induced toxic effects on haematological, biochemical, oxidative stress parameters and histopathological changes in Wistar rats,” Sci Rep, vol. 11, no. 1, p. 3911, Feb. 2021, doi: 10.1038/s41598-021-83316-8.
R. H. S. Da Silva et al., “Effects of coenzyme Q10 and N-acetylcysteine on experimental poisoning by paracetamol in Wistar rats,” PLoS ONE, vol. 18, no. 8, p. e0290268, Aug. 2023, doi: 10.1371/journal.pone.0290268.
C. Y. P. Ng, S. H. Cheng, and K. N. Yu, “Hormetic effect induced by depleted uranium in zebrafish embryos,” Aquatic Toxicology, vol. 175, pp. 184–191, Jun. 2016, doi: 10.1016/j.aquatox.2016.03.020.
M. Z. Hashmi, Naveedullah, C. Shen, and C. Yu, “Hormetic Responses of Food-Supplied PCB 31 to Zebrafish (Danio Rerio) Growth,” Dose-Response, vol. 13, no. 1, pp. 1–14, Jan. 2014, doi: 10.2203/dose-response.14-013.Chaofeng.
M. A. K. Abdelhalim and B. M. Jarrar, “Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis in the liver,” Lipids Health Dis, vol. 10, no. 1, p. 166, 2011, doi: 10.1186/1476-511X-10-166.
L. Hou, K. Liu, Y. Li, S. Ma, X. Ji, and L. Liu, “Necrotic pyknosis is a morphologically and biochemically distinct event from apoptotic pyknosis,” Journal of Cell Science, p. jcs.184374, Jan. 2016, doi: 10.1242/jcs.184374.
E. M. El Morsy and R. Kamel, “Protective effect of artichoke leaf extract against paracetamol-induced hepatotoxicity in rats,” Pharmaceutical Biology, vol. 53, no. 2, pp. 167–173, Feb. 2015, doi: 10.3109/13880209.2014.913066.
J. A. Hinson, D. W. Roberts, and L. P. James, “Mechanisms of Acetaminophen-Induced Liver Necrosis,” in Adverse Drug Reactions, vol. 196, J. Uetrecht, Ed., in Handbook of Experimental Pharmacology, vol. 196. , Berlin, Heidelberg: Springer Berlin Heidelberg, 2010, pp. 369–405. doi: 10.1007/978-3-642-00663-0_12.
C. I. Nosiri and G. Oze, “Liver Enzyme Levels of Paracetamol Induced Hepatotoxic Rats Treated with Aqueous Leaf Extract of Artocarpus Altilis,” The FASEB Journal, vol. 34, no. S1, pp. 1–1, Apr. 2020, doi: 10.1096/fasebj.2020.34.s1.09217.