Dose-Responsive Mitigation of Hepatic Oxidative Stress and Histopathological Damage by Channa striata Extract in Post-Carbon Tetrachloride-Exposed Rats
DOI:
10.29303/jppipa.v12i7.15899Published:
2026-07-25Downloads
Abstract
Carbon tetrachloride (CCl₄) is widely used to induce experimental oxidative liver injury through the generation of free radicals that promote lipid peroxidation and hepatocellular damage. Natural products with antioxidant properties are being explored for their potential to mitigate such injury. This study aimed to evaluate the dose-responsive ameliorative effects of Channa striata extract on hepatic oxidative stress and histopathological alterations in rats following subacute CCl₄ exposure. Thirty male Wistar rats were divided into five groups: normal control (K1), CCl₄ control (K2), and three treatment groups receiving C. striata extract at 100, 150, and 200 mg/kg body weight/day for two weeks after six weeks of CCl₄ induction (K3–K5). Hepatic malondialdehyde (MDA) levels were measured as an indicator of lipid peroxidation. Liver histopathology was assessed for hepatocellular necrosis, congestion, and inflammatory cell infiltration using a semi-quantitative scoring system. CCl₄ exposure significantly increased hepatic MDA levels and caused severe histopathological damage in the control group. C. striata extract dose-dependently attenuated MDA levels (p < 0.001), with the 200 mg/kg/day group showing the lowest levels (2.80 ± 0.15 vs. 6.65 ± 0.13 nmol/g in CCl₄ control). Histopathological scores for necrosis, congestion, and inflammatory infiltration ameliorated progressively with increasing doses, with median total scores improving from 8.5 (CCl₄ control) to 2.0 (200 mg/kg/day). Channa striata extract demonstrates dose-dependent ameliorative activity against established CCl₄-induced oxidative liver injury, as evidenced by attenuation of lipid peroxidation and mitigation of histopathological damage. Further studies incorporating serum liver enzymes and molecular mechanisms are warranted.
Keywords:
Ameliorative effect Carbon tetrachloride Channa striata Dose-response Hepatic oxidative stress Malondialdehyde (MDA)References
Abdulgani, N., Hidayati, D., Adinovitasary, R., Oliviatie, V., & Sekartaji, A. D. (2020). MDA levels in the pancreas, testes, liver, and plasma of diabetic rats: The effect of snakehead (Channa striata) extract. Nusantara Bioscience, 12(1), 50–54. https://doi.org/10.13057/nusbiosci/n120109
Abdulgani, N., Winarni, D., Darmanto, W., Hidayati, D., & Rojafi, M. Z. (2025). Antioxidant Effect of Snakehead Fish (Channa Striata) Albumin Extract on Diabetic Rats (Rattus Norvegicus). Trends in Sciences, 22(12). https://doi.org/10.48048/tis.2025.10834
Abdulkadir, M., Adam, A., Daniya, Z., & Sani, M. (2024). Hepatoprotective Effect of Ethanolic Extract of Rosemarinus officinalis (Rosemary) Leaves Against CCL4-induced Hepatic Damage in Albino Rats. Journal of Environmental Bioremediation and Toxicology, 7(2), 58–62. https://doi.org/10.54987/jebat.v7i2.1038
Algefare, A. I., Alfwuaires, M., Famurewa, A. C., Elsawy, H., & Sedky, A. (2024). Geraniol prevents CCl4-induced hepatotoxicity via suppression of hepatic oxidative stress, pro-inflammation and apoptosis in rats. Toxicology Reports, 12(May 2023), 128–134. https://doi.org/10.1016/j.toxrep.2024.01.007
Alkinani, K. B., Ali, E. M. M., Al-Shaikh, T. M., Awlia Khan, J. A., Al-Naomasi, T. M., Ali, S. S., Abduljawad, A. A., Mosa, O. F., & Zafar, T. A. (2021). Hepatoprotective Effects of (-) Epicatechin in CCl4-Induced Toxicity Model Are Mediated via Modulation of Oxidative Stress Markers in Rats. Evidence-Based Complementary and Alternative Medicine, 2021, 4655150. https://doi.org/10.1155/2021/4655150
Almeer, R. S., Albasher, G., Alotibi, F., Alarifi, S., Ali, D., & Alkahtani, S. (2019). Ziziphus spina-christi Leaf Extract Suppressed Mercury Chloride-Induced Nephrotoxicity via Nrf2-Antioxidant Pathway Activation and Inhibition of Inflammatory and Apoptotic Signaling. Oxidative Medicine and Cellular Longevity, 2019, 5634685. https://doi.org/10.1155/2019/5634685
Bedoui, A., Mufti, A., Feriani, A., Baccari, H., Bouallegue, A., Kharrat, M., Sobeh, M., Amri, M., & Abbes, Z. (2024). Unlocking the hepatoprotective potential of the parasitic plant Orobanche foetida Poir. aqueous extract against CCl4-induced liver injury in rat. Frontiers in Pharmacology, 14, 1320062. https://doi.org/10.3389/fphar.2023.1320062
Chupradit, S., Bokov, D., Zamanian, M. ., Heidari, M., & Hakimizadeh, E. (2022). Hepatoprotective and therapeutic effects of resveratrol: A focus on anti-inflammatory and antioxidative activities. Fundamental & Clinical Pharmacology, 36(3), 468–485. https://doi.org/10.1111/fcp.12746
Dai, C., Li, H., Wang, Y., Tang, S., Velkov, T., & Shen, J. (2021). Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury. Antioxidants, 10(6), 976. https://doi.org/10.3390/antiox10060976
Dai, C., Zhang, X., Lin, J., & Shen, J. (2023). Nootkatone supplementation ameliorates carbon tetrachloride-induced acute liver injury via inhibition of oxidative stress, NF-κB pathways, and activation of Nrf2/HO-1 pathway. Antioxidants, 12(1), 194. https://doi.org/10.3390/antiox12010194
El-Kot, S. M., Wanas, W., Hafez, A. M., Mahmoud, N. A., Tolba, A. M., Younis, A. H., El Sayed, G., & Abdelwahab, H. E. (2023). Effect of silymarin on the relative gene expressions of some inflammatory cytokines in the liver of CCl4-intoxicated male rats. Scientific Reports, 13, 15245. https://doi.org/10.1038/s41598-023-42250-7
Fahrudin, F., Ningsih, S., Wardhana, H. I., Haribowo, D. R., & Hamida, F. (2020). Efektivitas Dosis Karbon Tetraklorida (CCl4) Terhadap Tikus (Rattus norvegicus L.) Sebagai Hewan Model Fibrosis Hati. Berita Biologi, 19(3B), 411422. https://doi.org/10.14203/beritabiologi.v19i3b.3961
Hasnat, H., Shompa, S. ., Islam, M. ., Alam, S., Richi, F. ., Emon, N. ., Ashrafi, S., Ahmed, N. ., Chowdhury, M. N. ., Fatema, N., Hossain, M. ., Ghosh, A., & F, A. (2024). Flavonoids: A treasure house of prospective pharmacological potentials. Heliyon, 10(6), e27533. https://doi.org/10.1016/j.heliyon.2024.e27533
Jahan, I., Islam, M., Sarif, S., Amena, I., Shuvo, A., Akter, N., Chowdhury, F., Akter, R., Ahmed, I., Khan, F., Subhan, N., & Alam, M. (2023). Tempol Alters Antioxidant Enzyme Function, Modulates Multiple Genes Expression, and Ameliorates Hepatic and Renal Impairment in Carbon Tetrachloride (CCl4)-Intoxicated Rats. Livers, 3(1), 105–120. https://doi.org/10.3390/livers3010010
Javed, A., Mehboob, K., Rashid, A., Majid, A., Khan, S., & Baig, Z. (2023). Oxidative Stress and Lipid Peroxidation in NAFLD with and without Type 2 Diabetes Mellitus. Journal of the College of Physicians and Surgeons Pakistan, 33(11), 1254–1258. https://doi.org/10.29271/jcpsp.2023.11.1254
Johra, F. T., Hossain, S., Jain, P., Bristy, A. T., Emran, T., Ahmed, R., Sharker, S., Bepari, A. K., & Reza, H. M. (2023a). Amelioration of CCl 4 ‑ induced oxidative stress and hepatotoxicity by Ganoderma lucidum in Long Evans rats. Scientific Reports, 1–13. https://doi.org/10.1038/s41598-023-35228-y
Johra, F. T., Hossain, S., Jain, P., Bristy, A. T., Emran, T., Ahmed, R., Sharker, S., Bepari, A. K., & Reza, H. M. (2023b). Amelioration of _ CCl 4 _ induced oxidative stress and hepatotoxicity by Ganoderma lucidum in Long Evans rats. Scientific Reports, 1–13. https://doi.org/10.1038/s41598-023-35228-y
Kabbashi, A. S., Eltawaty, S. A., Ismail, A. M., Elshikh, A. A., Alrasheid, A. A., Elmahi, R. A., Koko, W. S., & Osman, E. E. (2024). Ethanolic Extract of Mangifera indica Protects against CCl4-Induced Hepatotoxicity via Antioxidant Capabilities in Albino Rats. Journal of Toxicology, 2024, 5539386. https://doi.org/10.1155/2024/5539386
Lee, V. L. L., Choo, B. K. M., Norazit, A., Noor, S. M., & Shaikh, M. F. (2022). Channa striatus in inflammatory conditions: A systematic review. Frontiers in Pharmacology, 13, 1–10. https://doi.org/10.3389/fphar.2022.1076143
Li, J., Song, D., Zhang, B., Guo, J., Li, W., Zhang, X., & Zhao, Q. (2021). Hepatoprotective Effects of Heracleum candicans Against Carbon Tetrachloride-Induced Acute Liver Injury in Rats. Dose-Response Hyphen, 19(3), 15593258211029510. https://doi.org/10.1177/1559325821102951
Li, N., Hao, L., Li, S., Deng, J., Yu, F., Zhang, J., Nie, A., & Hu, X. (2024). The NRF-2/HO-1 Signaling Pathway: A Promising Therapeutic Target for Metabolic Dysfunction-Associated Steatotic Liver Disease. Journal of Inflammation Research, 17, 8061–8083. https://doi.org/10.2147/JIR.S490418
Liao, Y., Lv, F., Quan, T., Wang, C., & Li, J. (2024). Flavonoids in natural products for the therapy of liver diseases: progress and future opportunities. Frontiers in Pharmacology, 15, 1485065. https://doi.org/10.3389/fphar.2024.1485065
Liu, H., Zhang, Y., & Ning, S. (2025). ScRNA-seq combined with ATAC-seq analysis to explore the metabolic balance mechanism of CCl4-induced liver inflammatory injury. Frontiers in Immunology, 16, 1600685. https://doi.org/10.3389/fimmu.2025.1600685
Mihajlovic, M., & Vinken, M. (2022). Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods. International Journal of Molecular Sciences, 23(6), 3315. https://doi.org/10.3390/ijms23063315
Munakarmi, S., Gurau, Y., Shrestha, J., Risal, P., Park, H. S., Shin, H. B., & Jeong, Y. J. (2022). Hepatoprotective Effects of a Natural Flavanol 3,3’-Diindolylmethane against CCl4-Induced Chronic Liver Injury in Mice and TGFβ1-Induced EMT in Mouse Hepatocytes via Activation of Nrf2 Cascade. International Journal of Molecular Sciences, 23(19), 11407. https://doi.org/10.3390/ijms231911407
Ogaly, H. A., Aldulmani, S. A. A., Al-Zahrani, F. A. M., & Abd-Elsalam, R. M. (2022). D-Carvone Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting Oxidative Stress and TGF-ß1/SMAD3 Signaling Pathway. Biology, 11(5), 739. https://doi.org/10.3390/biology11050739
Ouais, G. N., & Hassan, D. M. (2023). A comparative study on the hepatoprotective effect of selenium-nanoparticles and dates flesh extract on carbon tetrachloride induced liver damage in albino rats. Antomy & Cell Biology, 56(4), 583–551. https://doi.org/10.5115/acb.23.101
Pandey, B., Baral, R., & Kaundinnyayana, A. (2023). Promising hepatoprotective agents from the natural sources: a study of scientific evidence. Egyptian Liver Journal, 13, 14. https://doi.org/10.1186/s43066-023-00248-w
Pomacu, M. M., Trașcă, M. D., Pădureanu, V., Bugă, A. M., Andrei, A. M., Stănciulescu, E. C., Baniță, I. M., Rădulescu, D., & Pisoschi, C. G. (2021). Interrelation of inflammation and oxidative stress in liver cirrhosis. Experimental and Therapeutic Medicine, 21(6), 602. https://doi.org/10.3892/etm.2021.10034
Rahman, M., Molla, M., Sarker, M., Chowdhury, S., & Shaikh, M. (2018). Snakehead Fish (Channa striata) and Its Biochemical Properties and Health Benefits. SF Journal of Biotechnology and Biomedical Engineering, 1(1), 1–5. Retrieved from https://www.semanticscholar.org/paper/Snakehead-Fish-(Channa-striata)-and-Its-Biochemical/a0bc6c4fcaa273ee9a34eaf7d1e7834c600967ed
Ren, Z., Huo, Y., Zhang, Q., Chen, S., Lv, H., Peng, L., Wei, H., & Wan, C. (2021). Protective Effect of Lactiplantibacillus plantarum 1201 Combined with Galactooligosaccharide on Carbon Tetrachloride-Induced Acute Liver Injury in Mice. Nutrients, 13(12), 4441. https://doi.org/10.3390/nu13124441
Sarfo-Antwi, F., Larbie, C., Emikpe, B., & Appiah-Opong, R. (2024). Pericopsis laxiflora (Baker) stem bark extract is protective against carbon tetrachloride-induced acute liver damage by modulation of oxidative stress and inflammation. Journal of Taibah University for Science, 18. https://doi.org/10.1080/16583655.2024.2354569
Sharma, P., Nandave, M., Nandave, D., Yadav, S., Vargas-De-La-Cruz, C., Singh, S., Tandon, R., Ramniwas, S., & Behl, T. (2023). Reactive oxygen species (ROS)-mediated oxidative stress in chronic liver diseases and its mitigation by medicinal plants. American Journal of Translational Research, 15(11), 6321–6341. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/38074830%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC10703659
Ugwu, C. E., & Suru, S. M. (2021). Medicinal plants with hepatoprotective potentials against carbon tetrachloride-induced toxicity: a review. Egyptian Liver Journal, 11, 88. https://doi.org/10.1186/s43066-021-00161-0
Venmathi Maran, B. A., Iqbal, M., Gangadaran, P., Ahn, B., Rao, P. V., & Shah, M. D. (2022). Hepatoprotective Potential of Malaysian Medicinal Plants: A Review on Phytochemicals, Oxidative Stress, and Antioxidant Mechanisms. Molecules, 27(5), 1533. https://doi.org/10.3390/molecules27051533
Wang, B., Cui, S., Mao, B., Zhang, Q., Tian, F., Zhao, J., Tang, X., & Chen, W. (2022). Cyanidin Alleviated CCl4-Induced Acute Liver Injury by Regulating the Nrf2 and NF-κB Signaling Pathways. Antioxidants, 11(12), 2383. https://doi.org/10.3390/antiox11122383
Wang, Y., Zhang, Y., He, Y., Zhang, S., Huang, B., Wang, Y., Lin, W., Xiao, W., Zou, Z., & Cui, G. (2025). GGV formula attenuates CCl4-induced hepatic injury in mice by modulating the gut microbiota and metabolites. Frontiers in Nutrition, 12, 1564177. https://doi.org/10.3389/fnut.2025.156417
Weber, L. W., Boll, M., & Stampfl, A. (2003). Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Critical Reviews in Toxicology, 33(2), 105–136. https://doi.org/10.1080/713611034
Wei, X., Luo, C., He, Y., Huang, H., Ran, F., Liao, W., Tan, P., Fan, S., Cheng, Y., Zhang, D., Lin, J., & Han, L. (2021). Hepatoprotective Effects of Different Extracts From Triphala Against CCl4-Induced Acute Liver Injury in Mice. Frontiers in Pharmacology, 12, 664607. https://doi.org/10.3389/fphar.2021.664607
Xiao, J., Li, C., Pei, Y., Xu, S., Zhao, H., Xiang, W., & Wei, J. (2025). Lycium ruthenicum Polysaccharides Alleviate CCl4-Induced Acute Liver Injury Through Antioxidant and Anti-Inflammatory Effects. Nutrients, 17(21), 3359. https://doi.org/10.3390/nu17213359
Xu, Y., Zhang, Z., Wang, B., He, X., Tang, J., Peng, W., Zhou, J., & Wang, Y. (2022). Flammulinavelutipes Polysaccharides Modulate Gut Microbiota and Alleviate Carbon Tetrachloride-Induced Hepatic Oxidative Injury in Mice. Frontiers in Microbiology, 13, 847653. https://doi.org/10.3389/fmicb.2022.847653
Xue, Y., Deng, Q., Zhang, Q., Ma, Z., Chen, B., Yu, X., Peng, H., Yao, S., Liu, J., Ye, Y., & Pan, G. (2020). Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway. Scientific Reports, 10(1), 22265. https://doi.org/10.1038/s41598-020-79400-0
Yulizal, O., Lelo, A., Ilyas, S., & Kusumawati, R. L. (2020). The effect of Channa striata extract and standard eradication regimen on asymmetric dimethylarginine in Helicobacter pylori gastritis rat model. Veterinary World, 13(8), 1605–1612. https://doi.org/10.14202/vetworld.2020.1605-1612
Zawawi, N. Z. M., Shaari, R., Luqman Nordin, M., Hayati Hamdan, R., Peng, T. L., & Zalati, C. W. S. C. W. (2020). Antibacterial and cytotoxic activity assessment of Channa striatus (Haruan) extract. Veterinary World, 13(3), 508–514. https://doi.org/10.14202/vetworld.2020.508-514
Zhou, J., Zheng, Q., & Chen, Z. (2022). The Nrf2 Pathway in Liver Diseases. Frontiers in Cell and Developmental Biology, 10, 826204. https://doi.org/10.3389/fcell.2022.826204
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