Evaluation of Potential Toxicity of Calotropis gigantea Leaf Extract on Danio rerio: Bioactive Compounds, Oxidative Stress and Histological Toxicity Analysis
Abstract
A greater understanding of the ecotoxicological effects of plant-based products is required due to their increasing use. Despite its long-recognised medicinal properties, Calotropis gigantea possesses toxic characteristics that necessitate further investigation into its chemical composition and biological effects. This study evaluates the toxicity of crude C. gigantea leaf extracts on the freshwater fish Danio rerio over a 30-day exposure period. Alongside GC–MS analysis, which identified 48 major constituents, the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity were assessed using the DPPH assay. The extracts exhibited a higher flavonoid content than phenolic content, indicating strong antioxidant potential. In contrast, biochemical analyses revealed that exposed fish showed significantly elevated levels of oxidative stress biomarkers, including succinate dehydrogenase (SDH), glutathione S-transferase (GST), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), signifying cellular stress and disruption of redox homeostasis. Histological examinations of the liver, brain, muscle, and gills of treated fish demonstrated notable alterations. The gills exhibited lamellar fusion and epithelial lifting, impairing respiration. The brain showed neuronal vacuolation and degeneration, suggesting neurotoxicity, while muscle tissues displayed myofibrillar degeneration. Liver samples revealed hepatocyte necrosis and vacuolisation, indicative of metabolic dysfunction. Collectively, these enzymatic and systemic histopathological responses emphasise the toxicological impacts of C. gigantea extracts on aquatic organisms. The findings underscore the importance of ecotoxicological evaluations and the dual nature of medicinal plants such as C. gigantea, which can be both therapeutic and harmful. In addition to stressing the necessity for cautious application and further research to elucidate the mechanisms underlying their toxicity, this study provides valuable insights into the biological effects of plant-derived compounds.
Keywords:
Calotropis gigantea, Histology, Oxidative Stress, Phytochemical Analysis, Zebrafish
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References
Agarwal, S., Kaushik, S., Saha, H., Paramanick, D., Mazhar, M., Basist, P., ... & Alhalmi, A. (2025). Therapeutic potential of traditional herbal plants and their polyphenols in alleviation of mercury toxicity. Naunyn-Schmiedeberg's Archives of Pharmacology, 1-27. https://doi.org/10.1007/s00210-025-03807-7
Alara, O. R., Abdurahman, N. H., & Ukaegbu, C. I. (2018). Soxhlet extraction of phenolic compounds from Vernonia cinerea leaves and its antioxidant activity. Journal of Applied Research on Medicinal and Aromatic Plants, 11, 12-17. https://doi.org/10.1016/j.jarmap.2018.07.003
Ale, A., Bacchetta, C., Rossi, A. S., Galdopórpora, J., Desimone, M. F., de la Torre, F. R., ... & Cazenave, J. (2018). Nanosilver toxicity in gills of a neotropical fish: metal accumulation, oxidative stress, histopathology and other physiological effects. Ecotoxicology and Environmental Safety, 148, 976-984. https://doi.org/10.1016/j.ecoenv.2017.11.072
Ali, Z., Sher, N., Muhammad, I., Nayab, G. E., Alouffi, A., Almutairi, M. M., ... & Ali, A. (2025). The combined effect of cadmium and copper induces bioaccumulation, and toxicity and disrupts the antioxidant enzymatic activities of goldfish (Carassius auratus). Toxicology Reports, 14, 101972. https://doi.org/10.1016/j.toxrep.2025.101972
Alotaibi, S. S., Alshoaibi, D., Alamari, H., Albogami, S., Khan, E., Alshanbari, A., ... & Almalki, W. (2021). Potential significance of medicinal plants in forensic analysis: A review. Saudi Journal of Biological Sciences, 28(7), 3929-3935. https://doi.org/10.1016/j.sjbs.2021.03.071
Amer, S. A., El-Araby, D. A., Tartor, H., Farahat, M., Goda, N. I., Farag, M. F., ... & Osman, A. (2022). Long-term feeding with curcumin affects the growth, antioxidant capacity, immune status, tissue histoarchitecture, immune expression of proinflammatory cytokines, and apoptosis indicators in Nile tilapia, Oreochromis niloticus. Antioxidants, 11(5), 937. https://doi.org/10.3390/antiox11050937
Ansari, S. & Ansari, B. A. (2012). Alphamethrin toxicity: effect on the reproductive ability and the activities of phosphatases in the tissues of zebrafish, Danio rerio. International Journal of Life Science& Pharma Research 2, 89-100. https://ijlpr.com/index.php/journal/article/view/70/45
Arsad, S. S., Esa, N. M., & Hamzah, H. (2014). Histopathologic changes in liver and kidney tissues from male Sprague Dawley rats treated with Rhaphidophoradecursiva (Roxb.) Schott extract. J Cytol Histol S, 4(1), 1-6. https://doi.org/10.4172/2157-7099.S4-001
Aziz, S., Abdullah, S. (2023). Evaluation of Toxicity Induced by Engineered CuO Nanoparticles in Freshwater Fish, Labeorohita. Turkish Journal of Fisheries and Aquatic Sciences, 23(8), TRJFAS18762. https://doi.org/10.4194/TRJFAS18762.
Azzalini, E., Bernini, M., Vezzoli, S., Antonietti, A., &Verzeletti, A. (2019). A fatal case of self-poisoning through the ingestion of oleander leaves. Journal of Forensic and Legal Medicine, 65, 133-136. https://doi.org/10.1016/j.jflm.2019.05.016
Bergmeyer, H. U. (Ed.). (2012). Methods of enzymatic analysis. Elsevier. https://books.google.co.in/books?hl=en&lr=&id=GDd2zYuLpRwC&oi=fnd&pg=PP1&dq=Bergmeyer,+H.+U.+(Ed.).+(2012).+Methods+of+enzymatic+analysis.+Elsevier.+&ots=z5TFdpz3im&sig=6-l_t9ozEXEN9q3bI5dAwejJWc4&redir_esc=y#v=onepage&q&f=false
Brum, A., Cardoso, L., Chagas, E. C., Chaves, F. C. M., Mouriño, J. L. P., & Martins, M. L. (2018). Histological changes in Nile tilapia fed essential oils of clove basil and ginger after challenge with Streptococcus agalactiae. Aquaculture, 490, 98-107. https://doi.org/10.1016/j.aquaculture.2018.02.040
Carlberg, I. N. C. E. R., &Mannervik, B. E. N. G. T. (1975). Purification and characterization of the flavoenzyme glutathione reductase from rat liver. Journal of biological chemistry, 250(14), 5475-5480. https://www.jbc.org/article/S0021-9258(19)41206-4/pdf
Cheng, A. J., Yamada, T., Rassier, D. E., Andersson, D. C., Westerblad, H., & Lanner, J. T. (2016). Reactive oxygen/nitrogen species and contractile function in skeletal muscle during fatigue and recovery. The Journal of Physiology, 594(18), 5149-5160. https://doi.org/10.1113/jp270650
Chien, C., & Dauterman, W. C. (1991). Studies on glutathione S-transferase in Helicoverpa (= Heliothis) zea. Insect Biochemistry, 21(8), 857-864. https://doi.org/10.1016/0020-1790(91)90092-S
da Silva, A. P., Hernández, H. V. P., Comelli, C. L., Portugal, M. A. G., Delavy, F. M., de Souza, T. L., ... & de Castilhos Ghisi, N. (2024). Meta-analytical review of antioxidant mechanisms responses in animals exposed to herbicide 2, 4-D herbicide. Science of The Total Environment, 924, 171680. https://doi.org/10.1016/j.scitotenv.2024.171680
Dhawan, D., & Gupta, J. (2017). Research article comparison of different solvents for phytochemical extraction potential from datura metel plant leaves. International Journal of Biological Chemistry, 11(1), 17-22. https://doi.org/10.3923/ijbc.2017.17.22
Eula, M. A. C., Bayona-Serrano, J. D., Nishiyama-Jr, M. Y., Squaiella-Baptistão, C. C., Santoro, M. L., & Junqueira-de, I. D. L. M. (2025). The underestimated local effects of Micrurus corallinus venom revealed by gene expression and histopathological alterations. Toxicon, 108368. https://doi.org/10.1016/j.toxicon.2025.108368
Gulzar, R., Riaz, Z., Gillani, Q. U. A., Mehreen, A., Jameel, F., & Nawaz, R. (2023). Bioaccumulation and influence of cadmium chloride on histology of muscles and gills in Nile tilapia (Oreochromis niloticus). Journal of Survey in Fisheries Sciences, 10(2), 992-1000. https://doi.org/10.53555/sfs.v10i2.1509
Ismail, H. F., Hashim, Z., Soon, W. T., Ab Rahman, N. S., Zainudin, A. N., & Majid, F. A. A. (2017). Comparative study of herbal plants on the phenolic and flavonoid content, antioxidant activities and toxicity on cells and zebrafish embryo. Journal of Traditional and Complementary Medicine, 7(4), 452-465.https://doi.org/10.1016/j.jtcme.2016.12.006
Iyadurai, R., Gunasekaran, K., Jose, A., &Pitchaimuthu, K. (2020). Calotropis poisoning with severe cardiac toxicity A case report. Journal of Family Medicine and Primary Care, 9(8), 4444-4447. https://doi.org/10.4103/jfmpc.jfmpc_783_20
Jayalekshmi, C., Das, N. M., &Periakaruppan, R. (2024). Bioactive compounds of Calotropis gigantea for cancer treatment. Oral Oncology Reports, 10, 100336. https://doi.org/10.1016/j.oor.2024.100336
Ji, F., Zhang, J., Ding, X., Rong, L., Liu, X., Yan, T., & Li, J. (2024). Associations of GST gene polymorphisms and GST enzyme activity with the development of noise-induced hearing loss in Chinese han males. Public Health Genomics, 27(1), 168-176. https://doi.org/10.1159/000541618
Jomova, K., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2024). Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Archives of Toxicology, 98(5), 1323-1367. https://doi.org/10.1007/s00204-024-03696-4
Joshi, S. V., Gupta, S., Tripathi, K., Mishra, S., & Kumar, S. (2024). Antiviral plants of India. Ambika Prasad Research Foundation, Odisha, India.
Kanchan, T., & Atreya, A. (2016). Calotropis gigantea. Wilderness & Environmental Medicine, 27(2), 350-351. https://doi.org/10.1016/j.wem.2015.12.011
Kapoor, V. K., Kaur, N., & Rana, S. (2025). Safety concern of drugs of herbal origin. Phytochemistry Reviews, 1-16. https://doi.org/10.1007/s11101-025-10070-4
Kaur, R., & Dua, A. (2015). 96 h LC50, behavioural alterations and histopathological effects due to wastewater toxicity in a freshwater fish Channa punctatus. Environmental Science and Pollution Research, 22(7), 5100-5110. https://doi.org/10.1007/s11356-014-3710-1
Khasanah, N., Martono, E., Trisyono, Y. A., &Wijonarko, A. (2021). Toxicity and antifeedant activity of Calotropis gigantea L. leaf extract against PlutellaxylostellaL.(Lepidoptera: Plutellidae). International Journal of Design & Nature and Ecodynamics, 16(6), 677-682. https://doi.org/10.18280/ijdne.16060
King, T. E. (1967). [58] Preparation of succinate dehydrogenase and reconstitution of succinate oxidase. In Methods in enzymology (Vol. 10, pp. 322-331). Academic Press. https://doi.org/10.1016/0076-6879(67)10061-X
Kumari, P., Panda, P. K., Jha, E., Kumari, K., Nisha, K., Mallick, M. A., & Verma, S. K. (2017). Mechanistic insight to ROS and apoptosis regulated cytotoxicity inferred by green synthesized CuO nanoparticles from Calotropis gigantea to embryonic zebrafish. Scientific Reports, 7(1), 16284. https://doi.org/10.1038/s41598-017-16581-1
Lee, J. H., Kang, J. C., & Kim, J. H. (2023). Toxic effects of microplastic (Polyethylene) on fish: Accumulation, hematological parameters and antioxidant responses in Korean Bullhead, Pseudobagrusfulvidraco. Science of The Total Environment, 877, 162874. https://doi.org/10.1016/j.scitotenv.2023.162874
Mahale, D. S., Phulapagar, M., Gosavi, T., & Bharti, V. (2023). Review on Calotropis gigantea use on Diabetic. Research Journal of Pharmacology and Pharmacodynamics, 15(1), 36-41. https://doi.org/10.52711/2321-5836.2023.00008
Marklund, S., & Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European journal of biochemistry, 47(3), 469-474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
Miara, M. D., Bendif, H., Ait Hammou, M., & Teixidor-Toneu, I. (2018). Ethnobotanical survey of medicinal plants used by nomadic peoples in the Algerian steppe. Journal of ethnopharmacology, 219, 248-256. https://doi.org/10.1016/j.jep.2018.03.011
Tehrani H. S., & Moosavi-Movahedi A. A. (2018). Catalase and its mysteries. Progress in Biophysics and Molecular Biology, 140, 5-12. https://doi.org/10.1016/j.pbiomolbio.2018.03.001
Ni, H., Peng, L., Gao, X., Ji, H., Ma, J., Li, Y., & Jiang, S. (2019). Effects of maduramicin on adult zebrafish (Danio rerio): acute toxicity, tissue damage and oxidative stress. Ecotoxicology and environmental safety, 168, 249-259. https://doi.org/10.1016/j.ecoenv.2018.10.040
Nithaniyal, S., Majumder, S., Umapathy, S., & Parani, M. (2021). Forensic application of DNA barcoding in the identification of commonly occurring poisonous plants. Journal of forensic and legal medicine, 78, 102126. https://doi.org/10.1016/j.jflm.2021.102126
Oh, S. W., Kang, M. N., Cho, C. W., & Lee, M. W. (1997). Detection of carcinogenic amines from dyestuffs or dyed substrates. Dyes and Pigments, 33(2), 119-135. https://doi.org/10.1016/S0143-7208(96)00038-1
Olaleye, M. T., & Rocha, B. J. (2008). Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system. Experimental and Toxicologic Pathology, 59(5), 319-327. https://doi.org/10.1016/j.etp.2007.10.003
Panchamoorthy, R., Thada, R., & Chockalingam, S. (2022). Short-term Co-exposure of celery leaf powder exerts detoxifying action against acetaminophen-induced toxicity in fish gills. Journal of Hazardous Materials Advances, 8, 100148. https://doi.org/10.1016/j.hazadv.2022.100148
Perumal, S., Gopal Samy, M. V., & Subramanian, D. (2021). Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio). Journal of Biochemical and Molecular Toxicology, 35(9), e22843.https://doi.org/10.1002/jbt.22843
Sherikar, A. S., &Mahanthesh, M. C. (2015). Evaluation of aqueous and methanolic extract of leaves of Epipremnumaureum for radical scavenging activity by DPPH Method, total phenolic content, reducing capacity assay and FRAP assay. Journal of Pharmacognosy and Phytochemistry, 4(4), 36-40. https://www.phytojournal.com/archives/view-pdf/678/4-3-40
Shobana, C., Rangasamy, B., Poopal, R. K., Renuka, S., & Ramesh, M. (2018). Green synthesis of silver nanoparticles using Piper nigrum: tissue-specific bioaccumulation, histopathology, and oxidative stress responses in Indian major carp Labeorohita. Environmental Science and Pollution Research, 25(12), 11812-11832. https://doi.org/10.1007/s11356-018-1454-z
Subramanian, K., Sankaramourthy, D., & Gunasekaran, M. (2018). Toxicity studies related to medicinal plants. In Natural products and drug discovery (pp. 491-505). Elsevier. https://doi.org/10.1016/B978-0-08-102081-4.00018-6
Vašková, J., Kočan, L., Vaško, L., &Perjési, P. (2023). Glutathione-related enzymes and proteins: A review. Molecules, 28(3), 1447. https://doi.org/10.3390/molecules28031447
Verma, S. K., Nisha, K., Panda, P. K., Patel, P., Kumari, P., Mallick, M. A., ... & Das, B. (2020). Green synthesized MgO nanoparticles infer biocompatibility by reducing in vivo molecular nanotoxicity in embryonic zebrafish through arginine interaction elicited apoptosis. Science of The Total Environment, 713, 136521. https://doi.org/10.1016/j.scitotenv.2020.136521
Visweswaran, B., & Krishnamoorthy, G. (2012). Oxidative stress by tartrazine in the testis of Wistar rats. Journal of Pharmacy and Biological Sciences, 2(3), 44-49. https://www.iosrjournals.org/iosr-jpbs/papers/vol2-issue3/J0234447.pdf
Yang, Y., Dong, F., Liu, X., Xu, J., Wu, X., & Zheng, Y. (2020). Thifluzamide induces the toxic effects on zebrafish (Danio rerio) via inhibition of succinate dehydrogenase (SDH). Environmental Pollution, 265, 115031. https://doi.org/10.1016/j.envpol.2020.115031
Yousefi, M., Adineh, H., Al Sulivany, B. S., Gholamalipour Alamdari, E., Yilmaz, S., Mahboub, H. H., & Hoseini, S. M. (2025). The potential of the inclusion of Prosopis farcta extract in the diet on the growth performance, immunity, digestive enzyme activity, and oxidative status of the common carp, Cyprinus carpio, in response to Ammonia stress. Animals, 15(6), 895. https://doi.org/10.3390/ani15060895
Zhong, L., Liu, H., Zhang, H., Zhang, W., Li, M., Huang, Y., ... & Yin, L. (2022). High starch in diet leads to disruption of hepatic glycogen metabolism and liver fibrosis in largemouth bass (Micropterus salmoides), which is mediated by the PI3K/Akt signaling pathway. Frontiers in Physiology, 13, 880513. https://doi.org/10.3389/fphys.2022.880513
Alara, O. R., Abdurahman, N. H., & Ukaegbu, C. I. (2018). Soxhlet extraction of phenolic compounds from Vernonia cinerea leaves and its antioxidant activity. Journal of Applied Research on Medicinal and Aromatic Plants, 11, 12-17. https://doi.org/10.1016/j.jarmap.2018.07.003
Ale, A., Bacchetta, C., Rossi, A. S., Galdopórpora, J., Desimone, M. F., de la Torre, F. R., ... & Cazenave, J. (2018). Nanosilver toxicity in gills of a neotropical fish: metal accumulation, oxidative stress, histopathology and other physiological effects. Ecotoxicology and Environmental Safety, 148, 976-984. https://doi.org/10.1016/j.ecoenv.2017.11.072
Ali, Z., Sher, N., Muhammad, I., Nayab, G. E., Alouffi, A., Almutairi, M. M., ... & Ali, A. (2025). The combined effect of cadmium and copper induces bioaccumulation, and toxicity and disrupts the antioxidant enzymatic activities of goldfish (Carassius auratus). Toxicology Reports, 14, 101972. https://doi.org/10.1016/j.toxrep.2025.101972
Alotaibi, S. S., Alshoaibi, D., Alamari, H., Albogami, S., Khan, E., Alshanbari, A., ... & Almalki, W. (2021). Potential significance of medicinal plants in forensic analysis: A review. Saudi Journal of Biological Sciences, 28(7), 3929-3935. https://doi.org/10.1016/j.sjbs.2021.03.071
Amer, S. A., El-Araby, D. A., Tartor, H., Farahat, M., Goda, N. I., Farag, M. F., ... & Osman, A. (2022). Long-term feeding with curcumin affects the growth, antioxidant capacity, immune status, tissue histoarchitecture, immune expression of proinflammatory cytokines, and apoptosis indicators in Nile tilapia, Oreochromis niloticus. Antioxidants, 11(5), 937. https://doi.org/10.3390/antiox11050937
Ansari, S. & Ansari, B. A. (2012). Alphamethrin toxicity: effect on the reproductive ability and the activities of phosphatases in the tissues of zebrafish, Danio rerio. International Journal of Life Science& Pharma Research 2, 89-100. https://ijlpr.com/index.php/journal/article/view/70/45
Arsad, S. S., Esa, N. M., & Hamzah, H. (2014). Histopathologic changes in liver and kidney tissues from male Sprague Dawley rats treated with Rhaphidophoradecursiva (Roxb.) Schott extract. J Cytol Histol S, 4(1), 1-6. https://doi.org/10.4172/2157-7099.S4-001
Aziz, S., Abdullah, S. (2023). Evaluation of Toxicity Induced by Engineered CuO Nanoparticles in Freshwater Fish, Labeorohita. Turkish Journal of Fisheries and Aquatic Sciences, 23(8), TRJFAS18762. https://doi.org/10.4194/TRJFAS18762.
Azzalini, E., Bernini, M., Vezzoli, S., Antonietti, A., &Verzeletti, A. (2019). A fatal case of self-poisoning through the ingestion of oleander leaves. Journal of Forensic and Legal Medicine, 65, 133-136. https://doi.org/10.1016/j.jflm.2019.05.016
Bergmeyer, H. U. (Ed.). (2012). Methods of enzymatic analysis. Elsevier. https://books.google.co.in/books?hl=en&lr=&id=GDd2zYuLpRwC&oi=fnd&pg=PP1&dq=Bergmeyer,+H.+U.+(Ed.).+(2012).+Methods+of+enzymatic+analysis.+Elsevier.+&ots=z5TFdpz3im&sig=6-l_t9ozEXEN9q3bI5dAwejJWc4&redir_esc=y#v=onepage&q&f=false
Brum, A., Cardoso, L., Chagas, E. C., Chaves, F. C. M., Mouriño, J. L. P., & Martins, M. L. (2018). Histological changes in Nile tilapia fed essential oils of clove basil and ginger after challenge with Streptococcus agalactiae. Aquaculture, 490, 98-107. https://doi.org/10.1016/j.aquaculture.2018.02.040
Carlberg, I. N. C. E. R., &Mannervik, B. E. N. G. T. (1975). Purification and characterization of the flavoenzyme glutathione reductase from rat liver. Journal of biological chemistry, 250(14), 5475-5480. https://www.jbc.org/article/S0021-9258(19)41206-4/pdf
Cheng, A. J., Yamada, T., Rassier, D. E., Andersson, D. C., Westerblad, H., & Lanner, J. T. (2016). Reactive oxygen/nitrogen species and contractile function in skeletal muscle during fatigue and recovery. The Journal of Physiology, 594(18), 5149-5160. https://doi.org/10.1113/jp270650
Chien, C., & Dauterman, W. C. (1991). Studies on glutathione S-transferase in Helicoverpa (= Heliothis) zea. Insect Biochemistry, 21(8), 857-864. https://doi.org/10.1016/0020-1790(91)90092-S
da Silva, A. P., Hernández, H. V. P., Comelli, C. L., Portugal, M. A. G., Delavy, F. M., de Souza, T. L., ... & de Castilhos Ghisi, N. (2024). Meta-analytical review of antioxidant mechanisms responses in animals exposed to herbicide 2, 4-D herbicide. Science of The Total Environment, 924, 171680. https://doi.org/10.1016/j.scitotenv.2024.171680
Dhawan, D., & Gupta, J. (2017). Research article comparison of different solvents for phytochemical extraction potential from datura metel plant leaves. International Journal of Biological Chemistry, 11(1), 17-22. https://doi.org/10.3923/ijbc.2017.17.22
Eula, M. A. C., Bayona-Serrano, J. D., Nishiyama-Jr, M. Y., Squaiella-Baptistão, C. C., Santoro, M. L., & Junqueira-de, I. D. L. M. (2025). The underestimated local effects of Micrurus corallinus venom revealed by gene expression and histopathological alterations. Toxicon, 108368. https://doi.org/10.1016/j.toxicon.2025.108368
Gulzar, R., Riaz, Z., Gillani, Q. U. A., Mehreen, A., Jameel, F., & Nawaz, R. (2023). Bioaccumulation and influence of cadmium chloride on histology of muscles and gills in Nile tilapia (Oreochromis niloticus). Journal of Survey in Fisheries Sciences, 10(2), 992-1000. https://doi.org/10.53555/sfs.v10i2.1509
Ismail, H. F., Hashim, Z., Soon, W. T., Ab Rahman, N. S., Zainudin, A. N., & Majid, F. A. A. (2017). Comparative study of herbal plants on the phenolic and flavonoid content, antioxidant activities and toxicity on cells and zebrafish embryo. Journal of Traditional and Complementary Medicine, 7(4), 452-465.https://doi.org/10.1016/j.jtcme.2016.12.006
Iyadurai, R., Gunasekaran, K., Jose, A., &Pitchaimuthu, K. (2020). Calotropis poisoning with severe cardiac toxicity A case report. Journal of Family Medicine and Primary Care, 9(8), 4444-4447. https://doi.org/10.4103/jfmpc.jfmpc_783_20
Jayalekshmi, C., Das, N. M., &Periakaruppan, R. (2024). Bioactive compounds of Calotropis gigantea for cancer treatment. Oral Oncology Reports, 10, 100336. https://doi.org/10.1016/j.oor.2024.100336
Ji, F., Zhang, J., Ding, X., Rong, L., Liu, X., Yan, T., & Li, J. (2024). Associations of GST gene polymorphisms and GST enzyme activity with the development of noise-induced hearing loss in Chinese han males. Public Health Genomics, 27(1), 168-176. https://doi.org/10.1159/000541618
Jomova, K., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2024). Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Archives of Toxicology, 98(5), 1323-1367. https://doi.org/10.1007/s00204-024-03696-4
Joshi, S. V., Gupta, S., Tripathi, K., Mishra, S., & Kumar, S. (2024). Antiviral plants of India. Ambika Prasad Research Foundation, Odisha, India.
Kanchan, T., & Atreya, A. (2016). Calotropis gigantea. Wilderness & Environmental Medicine, 27(2), 350-351. https://doi.org/10.1016/j.wem.2015.12.011
Kapoor, V. K., Kaur, N., & Rana, S. (2025). Safety concern of drugs of herbal origin. Phytochemistry Reviews, 1-16. https://doi.org/10.1007/s11101-025-10070-4
Kaur, R., & Dua, A. (2015). 96 h LC50, behavioural alterations and histopathological effects due to wastewater toxicity in a freshwater fish Channa punctatus. Environmental Science and Pollution Research, 22(7), 5100-5110. https://doi.org/10.1007/s11356-014-3710-1
Khasanah, N., Martono, E., Trisyono, Y. A., &Wijonarko, A. (2021). Toxicity and antifeedant activity of Calotropis gigantea L. leaf extract against PlutellaxylostellaL.(Lepidoptera: Plutellidae). International Journal of Design & Nature and Ecodynamics, 16(6), 677-682. https://doi.org/10.18280/ijdne.16060
King, T. E. (1967). [58] Preparation of succinate dehydrogenase and reconstitution of succinate oxidase. In Methods in enzymology (Vol. 10, pp. 322-331). Academic Press. https://doi.org/10.1016/0076-6879(67)10061-X
Kumari, P., Panda, P. K., Jha, E., Kumari, K., Nisha, K., Mallick, M. A., & Verma, S. K. (2017). Mechanistic insight to ROS and apoptosis regulated cytotoxicity inferred by green synthesized CuO nanoparticles from Calotropis gigantea to embryonic zebrafish. Scientific Reports, 7(1), 16284. https://doi.org/10.1038/s41598-017-16581-1
Lee, J. H., Kang, J. C., & Kim, J. H. (2023). Toxic effects of microplastic (Polyethylene) on fish: Accumulation, hematological parameters and antioxidant responses in Korean Bullhead, Pseudobagrusfulvidraco. Science of The Total Environment, 877, 162874. https://doi.org/10.1016/j.scitotenv.2023.162874
Mahale, D. S., Phulapagar, M., Gosavi, T., & Bharti, V. (2023). Review on Calotropis gigantea use on Diabetic. Research Journal of Pharmacology and Pharmacodynamics, 15(1), 36-41. https://doi.org/10.52711/2321-5836.2023.00008
Marklund, S., & Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European journal of biochemistry, 47(3), 469-474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
Miara, M. D., Bendif, H., Ait Hammou, M., & Teixidor-Toneu, I. (2018). Ethnobotanical survey of medicinal plants used by nomadic peoples in the Algerian steppe. Journal of ethnopharmacology, 219, 248-256. https://doi.org/10.1016/j.jep.2018.03.011
Tehrani H. S., & Moosavi-Movahedi A. A. (2018). Catalase and its mysteries. Progress in Biophysics and Molecular Biology, 140, 5-12. https://doi.org/10.1016/j.pbiomolbio.2018.03.001
Ni, H., Peng, L., Gao, X., Ji, H., Ma, J., Li, Y., & Jiang, S. (2019). Effects of maduramicin on adult zebrafish (Danio rerio): acute toxicity, tissue damage and oxidative stress. Ecotoxicology and environmental safety, 168, 249-259. https://doi.org/10.1016/j.ecoenv.2018.10.040
Nithaniyal, S., Majumder, S., Umapathy, S., & Parani, M. (2021). Forensic application of DNA barcoding in the identification of commonly occurring poisonous plants. Journal of forensic and legal medicine, 78, 102126. https://doi.org/10.1016/j.jflm.2021.102126
Oh, S. W., Kang, M. N., Cho, C. W., & Lee, M. W. (1997). Detection of carcinogenic amines from dyestuffs or dyed substrates. Dyes and Pigments, 33(2), 119-135. https://doi.org/10.1016/S0143-7208(96)00038-1
Olaleye, M. T., & Rocha, B. J. (2008). Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system. Experimental and Toxicologic Pathology, 59(5), 319-327. https://doi.org/10.1016/j.etp.2007.10.003
Panchamoorthy, R., Thada, R., & Chockalingam, S. (2022). Short-term Co-exposure of celery leaf powder exerts detoxifying action against acetaminophen-induced toxicity in fish gills. Journal of Hazardous Materials Advances, 8, 100148. https://doi.org/10.1016/j.hazadv.2022.100148
Perumal, S., Gopal Samy, M. V., & Subramanian, D. (2021). Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio). Journal of Biochemical and Molecular Toxicology, 35(9), e22843.https://doi.org/10.1002/jbt.22843
Sherikar, A. S., &Mahanthesh, M. C. (2015). Evaluation of aqueous and methanolic extract of leaves of Epipremnumaureum for radical scavenging activity by DPPH Method, total phenolic content, reducing capacity assay and FRAP assay. Journal of Pharmacognosy and Phytochemistry, 4(4), 36-40. https://www.phytojournal.com/archives/view-pdf/678/4-3-40
Shobana, C., Rangasamy, B., Poopal, R. K., Renuka, S., & Ramesh, M. (2018). Green synthesis of silver nanoparticles using Piper nigrum: tissue-specific bioaccumulation, histopathology, and oxidative stress responses in Indian major carp Labeorohita. Environmental Science and Pollution Research, 25(12), 11812-11832. https://doi.org/10.1007/s11356-018-1454-z
Subramanian, K., Sankaramourthy, D., & Gunasekaran, M. (2018). Toxicity studies related to medicinal plants. In Natural products and drug discovery (pp. 491-505). Elsevier. https://doi.org/10.1016/B978-0-08-102081-4.00018-6
Vašková, J., Kočan, L., Vaško, L., &Perjési, P. (2023). Glutathione-related enzymes and proteins: A review. Molecules, 28(3), 1447. https://doi.org/10.3390/molecules28031447
Verma, S. K., Nisha, K., Panda, P. K., Patel, P., Kumari, P., Mallick, M. A., ... & Das, B. (2020). Green synthesized MgO nanoparticles infer biocompatibility by reducing in vivo molecular nanotoxicity in embryonic zebrafish through arginine interaction elicited apoptosis. Science of The Total Environment, 713, 136521. https://doi.org/10.1016/j.scitotenv.2020.136521
Visweswaran, B., & Krishnamoorthy, G. (2012). Oxidative stress by tartrazine in the testis of Wistar rats. Journal of Pharmacy and Biological Sciences, 2(3), 44-49. https://www.iosrjournals.org/iosr-jpbs/papers/vol2-issue3/J0234447.pdf
Yang, Y., Dong, F., Liu, X., Xu, J., Wu, X., & Zheng, Y. (2020). Thifluzamide induces the toxic effects on zebrafish (Danio rerio) via inhibition of succinate dehydrogenase (SDH). Environmental Pollution, 265, 115031. https://doi.org/10.1016/j.envpol.2020.115031
Yousefi, M., Adineh, H., Al Sulivany, B. S., Gholamalipour Alamdari, E., Yilmaz, S., Mahboub, H. H., & Hoseini, S. M. (2025). The potential of the inclusion of Prosopis farcta extract in the diet on the growth performance, immunity, digestive enzyme activity, and oxidative status of the common carp, Cyprinus carpio, in response to Ammonia stress. Animals, 15(6), 895. https://doi.org/10.3390/ani15060895
Zhong, L., Liu, H., Zhang, H., Zhang, W., Li, M., Huang, Y., ... & Yin, L. (2022). High starch in diet leads to disruption of hepatic glycogen metabolism and liver fibrosis in largemouth bass (Micropterus salmoides), which is mediated by the PI3K/Akt signaling pathway. Frontiers in Physiology, 13, 880513. https://doi.org/10.3389/fphys.2022.880513
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B., G., & Paari, K. (2025). Evaluation of Potential Toxicity of Calotropis gigantea Leaf Extract on Danio rerio: Bioactive Compounds, Oxidative Stress and Histological Toxicity Analysis. International Journal of Advancement in Life Sciences Research, 8(4), 111-127. https://doi.org/https://doi.org/10.31632/ijalsr.2025.v08i04.009
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