Acute styrene exposure induces hepatocellular injury and molecular stress responses in Oryzias celebensis: Evidence for a tropical sentinel species in ecotoxicological monitoring

Vet World Vol.18 December-2025 Article - 17

Research Article

Veterinary World, 18(12): 3902-3913

https://doi.org/10.14202/vetworld.2025.3902-3913

Amelia Ramadhani Anshar^1,2

, Huda Shalahudin Darusman^3,4

, Wasmen Manalu⁵

, Khusnul Yaqin⁶

, Muhammad Ardiansyah Nurdin⁷

, and Muhammad Reza Cordova^8,9

1. Animal Biomedical Sciences Study Program, School of Veterinary and Biomedical Sciences, IPB University, Bogor, 16680, Indonesia.

2. Veterinary Medicine Study Program, Hasanuddin University, Makassar, 90245, Indonesia. .

3. Division of Pharmacology and Toxicology, School of Veterinary and Biomedical Sciences, IPB University, Bogor, 16680, Indonesia.

4. Primate Research Center, Institute of Research and Community Service, IPB University, Bogor, 16151, Indonesia. .

5. Division of Physiology, School of Veterinary and Biomedical Sciences, IPB University, Bogor, 16680, Indonesia. .

6. Aquatic Resources Management Study Program, Hasanuddin University, Makassar, 90245, Indonesia.

7. Veterinary Medicine Study Program, Hasanuddin University, Makassar, 90245, Indonesia. .

8. Research Center for Oceanography, National Research and Innovation Agency, Jakarta, 14430, Indonesia.

9. Research Center for Oceanology, National Research and Innovation Agency, Tangerang Selatan, 15314, Indonesia. .

Background and Aim: Plastic-derived monomers such as styrene are increasingly detected in tropical freshwater ecosystems at concentrations approaching 0.8 mg/L. These contaminants pose toxicological risks to aquatic organisms, particularly through oxidative stress, inflammation, and metabolic disruption. Oryzias celebensis (Celebes medaka), an endemic tropical freshwater species, offers high ecological relevance for assessing pollutant impacts in Southeast Asia. This study evaluated the hepatic histopathological and molecular responses of O. celebensis following acute styrene exposure and assessed its suitability as a tropical sentinel species.

Materials and Methods: Adult O. celebensis were exposed to 0.1, 0.25, 0.5, and 0.75 mg/L styrene for 96 h under semi-static conditions. Liver tissues were examined for cytoplasmic vacuolization, necrosis, inflammatory cell infiltration, and congestion using standard histopathological scoring. Expression of biomarker genes related to detoxification (cytochrome P450 1A1 [CYP1A1]), oxidative stress (catalase, superoxide dismutase [SOD]), and inflammation (tumor necrosis factor [TNF]) was quantified using reverse transcription quantitative polymerase chain reaction. Correlations between biomarker expression and tissue lesions were analyzed using Spearman’s coefficients.

Results: Styrene exposure induced concentration-dependent hepatic injury. Histopathological lesions intensified markedly at ≥0.5 mg/L, with prominent vacuolization, necrosis, and inflammatory infiltration. CYP1A1 was strongly upregulated, showing a 36.9-fold increase at 0.75 mg/L (p < 0.01), indicating robust activation of the aryl hydrocarbon receptor (AhR) pathway. Antioxidant enzymes (catalase and SOD) and TNF expression also increased significantly, reflecting oxidative and inflammatory stress. Strong positive correlations (rₛ = 0.93–0.99) were observed between gene expression and lesion severity, confirming mechanistic links between molecular responses and tissue pathology.

Conclusion: Acute styrene exposure triggers coordinated hepatocellular injury and molecular stress responses in O. celebensis through activation of aryl hydrocarbon receptor-CYP1A1, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. The strong correspondence between histopathological and transcriptional biomarkers demonstrates that this species is highly sensitive to styrene toxicity and suitable for ecotoxicological monitoring. Findings highlight the need for environmental surveillance of industrial pollutants in tropical freshwater systems.

Keywords: CYP1A1, ecotoxicology, hepatotoxicity, inflammation, molecular biomarkers, Oryzias celebensis, oxidative stress, plastic-derived pollutants, styrene toxicity, tropical freshwater fish.

How to cite this article: Anshar AR, Darusman HS, Manalu W, Yaqin K, Nurdin MA, and Cordova MR (2025) Acute styrene exposure induces hepatocellular injury and molecular stress responses in Oryzias celebensis: Evidence for a tropical sentinel species in ecotoxicological monitoring, Veterinary World, 18(12): 3902–3913.

Received: 02-08-2025 Accepted: 14-11-2025 Published online: 14-12-2025

Corresponding author: Amelia Ramadhani Anshar E-mail: ameliaanshar@med.unhas.ac.id

DOI: 10.14202/vetworld.2025.3902-3913

Copyright: Anshar, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.