Skip to main content
Have a personal or library account? Click to login
Combined toxicity of copper–nickel co-exposure on growth, digestive function, antioxidant status, and transporter- and inflammation-related gene expression responses in Oreochromis niloticus, with potential mitigation by watermelon rind (Citrullus lanatus) Cover

Combined toxicity of copper–nickel co-exposure on growth, digestive function, antioxidant status, and transporter- and inflammation-related gene expression responses in Oreochromis niloticus, with potential mitigation by watermelon rind (Citrullus lanatus)

Open Access
|Nov 2026
Read online

References

  1. Abdel-Hamid, E. A. A., Hashem, S. H., & Ghareib, A. A. (2021). The effect of a mixture of environmental pollutants on some biomarkers in the Nile tilapia (Oreochromis niloticus). Egyptian Journal of Aquatic Biology and Fisheries, 25(2), 665–681. https://doi.org/10.21608/ejabf.2021.166982
  2. Abdel Rahman, A. N., Sobh, M. S., Mansour, A. T., AlSaqufi, A. S., Alkhamis, Y., Hassanien, H. A., Abbas, A., Khamis, T., Ibrahim, R. E., & Elazab, S. T. (2025). Protective effects of dietary Cucurbita pepo on oxidative damage, histopathological alterations, and endoplasmic reticulum stress in the brain and gills of Oreochromis niloticus exposed to trace elements. Veterinary Research Communications, 50, 79. https://doi.org/10.1007/s11259-025-11019-w
  3. Abou-Hadeed, A., Ibrahim, K., El-Sharkawy, N., Saleh Sakr, F., & Abd El-Hamed, S. (2008). Experimental studies on nickel toxicity in Nile tilapia health. 8th International Symposium on Tilapia in Aquaculture.
  4. Agbana, J. A. (2023). Watermelon rind (Citrullus lanatus) supplementation improves growth performance of pigs via enhanced nutrient transporters gene expression. International Journal of Advanced Academic Research, 9(10), 37–43.
  5. Ahmed, S. A. A., El-Rahman, G. I. A., Mohammed, H. A., Abdo, S. A., Aly, M. Y. M., Ghannam, H. E., Mahsoub, F., Khamis, T., & Ibrahim, R. E. (2025). The ability of dietary essential oils to mitigate nickel-induced growth retardation, immune-antioxidant suppression, and endoplasmic reticulum stress activation in Nile tilapia. Fish Physiology and Biochemistry, 51(2), 76. https://doi.org/10.1007/s10695-025-01482-2
  6. Al-Sayed, H. M., & Ahmed, A. R. (2013). Utilization of watermelon rinds and sharlyn melon peels as a natural source of dietary fiber and antioxidants in cake. Annals of Agricultural Sciences, 58(1), 83–95. https://doi.org/10.1016/j.aoas.2013.01.012
  7. Alsuwayt, B. (2025). Polyphenol-rich Citrullus lanatus rind extract mitigates doxorubicin-induced cardiotoxicity: HPLC profiling and in vivo evaluation. Pharmaceutics, 17, 1469. https://doi.org/10.3390/pharmaceutics17111469
  8. AOAC (2005). Official methods of analysis of association of official analytical chemists (18th ed.). Association of Official Analytical Chemists, Washington, DC, USA.
  9. APHA (2005). Standard methods for examination of water and wastewater (21st ed.). American Public Health Association, New York, USA.
  10. Ashoka, S., Begum, S. S., Ray, B. R. M., & Muthuraju, M. (2022). Nutritional evaluation of watermelon (Citrullus lanatus) rind petha for its sensory, shelf-life and consumer acceptability. Asian Journal of Dairy and Food Research, 41(2), 225–230. https://doi.org/10.18805/ajdfr.DR-1737
  11. AVMA (2007). Guidelines on Euthanasia. American Veterinary Medical Association. https://www.avma.org/issues/animal_welfare/euthanasia.pdf
  12. Bahrudin, M., Al Fauzi, A., & Sugianto, P. (2025). Effectiveness of red watermelon in preventing atherosclerosis through the role of lipids, PCSK9, LOX-1, CD36, and ABCA1 in Wistar rats. Current Issues in Molecular Biology, 47(6), 433. https://doi.org/10.3390/cimb47060433
  13. Ben Romdhane, M., Bouallegue, A., Bourhia, M., Bougatef, A., Salamatullah, A., Ellouz-Chaabouni, S., & Haddar, A. (2024). Watermelon rind dietary fibers as natural source to enhance texture of wheat bread. Foods, 13(18), 2909. https://doi.org/10.3390/foods13182909
  14. Bernfeld, P. (1955). Amylases, α and β. Methods in Enzymology, 1, 149–158. https://dx.doi.org/10.1016/0076-6879(55)01021-5
  15. Bersin, T. V., Cordova, K. L., Journey, M. L., Beckman, B. R., & Lema, S. C. (2024). Food deprivation reduces sensitivity of liver Igf1 synthesis pathways to growth hormone in juvenile gopher rockfish (Sebastes carnatus). General and Comparative Endocrinology, 346, 114404. https://dx.doi.org/0.1016/j.ygcen.2023.114404
  16. Bhat, R. A., Alam, A., Jha, D. N., Kumar, V., Kumar, J., Thakur, V. R., & Das, B. K. (2025). Fate and effects of heavy metals in fishes: antioxidant defense system, miRNA/gene expression response, and histopathological reproductive manifestations. Biological Trace Element Research, 203, 4326–4346. https://doi.org/10.1007/s12011-024-04478-w
  17. Canosa, L. F., & Bertucci, J. I. (2023). The effect of environmental stressors on growth in fish and its endocrine control. Frontiers in Endocrinology, 14, 1109461. https://doi.org/10.3389/fendo.2023.1109461
  18. Caputo, M., Pigni, S., Agosti, E., Daffara, T., Ferrero, A., Filigheddu, N., & Prodam, F. (2021). Regulation of GH and GH signaling by nutrients. Cells, 10(6), 1376. https://doi.org/10.3390/cells10061376
  19. Copeland, D. L., Duff, R. J., Liu, Q., Prokop, J., & Londraville, R. L. (2011). Leptin in teleost fishes: an argument for comparative study. Frontiers in Physiology, 2, 26. https://doi.org/10.3389/fphys.2011.00026
  20. Das, J. N., & Saikia, S. (2024). Metal induced oxidative stress in fishes: A review. Journal of Advanced Zoology, 45(1), 434–449. https://doi.org/10.53555/jaz.v45i1.3582
  21. Doan, H. V., Lumsangkul, C., Hoseinifar, S. H., Hung, T. Q., Stejskal, V., Ringø, E., Dawood, M. A. O., & Esteban, M. Á. (2020). Administration of watermelon rind powder to Nile tilapia (Oreochromis niloticus) culture under biofloc system: Effect on growth performance, innate immune response, and disease resistance. Aquaculture, 528, 735574. https://doi.org/10.1016/j.aquaculture.2020.735574
  22. Doan, H. V., Hoseinifar, S. H., Naraballobh, W., Paolucci, M., Wongmaneeprateep, S., Charoenwattanasak, S., Dawood, M. A. O., & Abdel-Tawwab, M. (2021). Dietary inclusion of watermelon rind powder and Lactobacillus plantarum: Effects on Nile tilapia’s growth, skin mucus and serum immunities, and disease resistance. Fish and Shellfish Immunology, 116, 107–114. https://doi.org/10.1016/j.fsi.2021.07.003
  23. El-Houseiny, W., Khalil, A. A., Abd-Elhakim, Y. M., Arisha, A. H., Moselhy, A. A. A., Dahshan, H., Saber, T., Saber, T. M., & Ahmed, M. M. (2022). Alleviative effects of dietary Silybum marianum and co-enzyme Q10 on waterborne nickel-induced impaired growth, immunosuppression, tissue damage, immune-related genes dysregulation, and reduced resistance to Pseudomonas aeruginosa in Oreochromis niloticus. Aquaculture Reports, 26, 101308. https://doi.org/10.1016/j.aqrep.2022.101308
  24. El-Sayed, A.-F., & Fitzsimmons, K. (2023). From Africa to the world – the journey of Nile tilapia. Reviews in Aquaculture, 15(1), 6–21. https://doi.org/10.1111/raq.12738
  25. FAO (2026). Cultured Aquatic Species Information Programme – Oreochromis niloticus. Oreochromis niloticus (Linnaeus 1758) (J. E. Rakocy, Text). Fisheries and Aquaculture Department. http://www.fao.org/fishery/culturedspecies/oreochromis_niloticus/en
  26. Fernandez-Botran, R., Gorantla, V., Sun, X., Ren, X., Perez-Abadia, G., Crespo, F. A., Oliver, R., Orhun, H. I., Quan, E. E., & Maldonado, C. (2002). Targeting of glycosaminoglycan-cytokine interactions as a novel therapeutic approach in allotransplantation. Transplantation, 74(5), 623–629. https://doi.org/10.1097/00007890-200209150-00007.
  27. Gao, S., Sun, P., Zhao, X., Chang, K., & Chen, W. (2023). Waterborne copper exposure decreases fish growth and survival by promoting gills and liver impairments in largemouth bass (Micropterus salmoides). Environmental Science and Pollution Research, 30(5), 119204–119216. https://doi.org/10.1007/s11356-023-30755-7
  28. Gong, N., Lundin, J., Morgenroth, D., Sheridan, M., Sandblom, E., & Björnsson, B. (2022). Roles of leptin in initiation of acquired growth hormone resistance and control of metabolism in rainbow trout. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 322(5), R434–R444. https://doi.org/10.1152/ajpregu.00254.2021
  29. Gorbanalinejad, V., Nobakht, A. (2017). The effects of different levels of watermelon skin with and without enzyme, on performance, carcass traits, blood biochemical parameters and immune status of broilers. Iranian Journal of Animal Science Research, 9(1), 57–72. https://doi.org/10.22067/ijasr.v9i1.57242
  30. Gu, I., Balogun, O., Brownmiller, C., Kang, H. W., & Lee, S.-O. (2023). Bioavailability of citrulline in watermelon flesh, rind, and skin using a human intestinal epithelial Caco-2 cell model. Applied Sciences, 13(8), 4882. https://doi.org/10.3390/app13084882
  31. Guillen, J., Asche, F., Borriello, A., Carvalho, N., Druon, J.-N., Garlock, T., Llorente, I., & Macias, D. (2025). What is happening to the European Union aquaculture production? Investigating its stagnation and sustainability. Aquaculture, 596, 741793. https://doi.org/10.1016/j.aquaculture.2024.741793
  32. Guo, H., Chen, L., Cui, H., Peng, X., Fang, J., Zuo, Z., Deng, J., Wang, X., & Wu, B. (2015). Research advances on pathways of nickel-induced apoptosis. International Journal of Molecular Sciences, 17(1), 10. https://doi.org/10.3390/ijms17010010
  33. Guo, H., Liu, H., Jian, Z., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., Zhao, L., Geng, Y., Ouyang, P., Lai, W., Chen, Z., & Huang, C. (2019). Nickel induces inflammatory activation via NF-κB, MAPKs, IRF3 and NLRP3 inflammasome signaling pathways in macrophages. Aging, 11(23), 11659–11672. https://doi.org/10.18632/aging.102570
  34. Haque, M. M., & Mahmud, M. N. (2025). Potential role of aquaculture in advancing sustainable development goals (SDGs) in Bangladesh. Aquaculture Research, 2025, 6035730. https://doi.org/10.1155/are/6035730
  35. Hu, X., Ma, W., Zhang, D., Tian, Z., Yang, Y., Huang, Y., & Hong, Y. (2025). Application of natural antioxidants as feed additives in aquaculture: A review. Biology, 14(2), 87. https://doi.org/10.3390/biology14010087
  36. Huang, Q., Vera Delgado, J. M., Seni Pinoargote, O. D., & Llaguno, R. A. (2015). Molecular evolution of the Slc15 family and its response to waterborne copper and mercury exposure in tilapia. Aquatic Toxicology, 163, 140–147. https://doi.org/10.1016/j.aquatox.2015.04.011
  37. Iheanacho, S. C., Ikwo, T. K., Igweze, N. O., & Ogueji, E. O. (2018). Effect of different dietary inclusion levels of melon seed (Citrullus lanatus) peel on growth, haematology and histology of Oreochromis niloticus juvenile. Turkish Journal of Fisheries and Aquatic Sciences, 18, 377–384. https://doi.org/10.4194/1303-2712-v18_3_03
  38. Jiang, W. D., Liu, Y., Hu, K., Jiang, J., Li, S. H., Feng, L., & Zhou, X. Q. (2014). Copper exposure induces oxidative injury, disturbs the antioxidant system and changes the Nrf2/ARE (CuZnSOD) signaling in the fish brain: protective effects of myo-inositol. Aquatic Toxicology, 155, 301–313. https://doi.org/10.1016/j.aquatox.2014.07.003
  39. Jiang, W. D., Liu, Y., Jiang, J., Wu, P., Feng, L., & Zhou, X. Q. (2015). Copper exposure induces toxicity to the antioxidant system via the destruction of Nrf2/ARE signaling and caspase-3-regulated DNA damage in fish muscle: amelioration by myo-inositol. Aquatic Toxicology, 159, 245–255. https://doi.org/10.1016/j.aquatox.2014.12.020
  40. Kakade, A., Sharma, M., Salama, E.-S., Zhang, P., Zhang, L., Xing, X., Yue, J., Song, Z., Nan, L., Yujun, S., & Li, X. (2023). Heavy metals (HMs) pollution in the aquatic environment: Role of probiotics and gut microbiota in HMs remediation. Environmental Research, 223, 115186. https://doi.org/10.1016/j.envres.2022.115186
  41. Kang, T., Zhao, S., Shi, L., & Li, J. (2021). Glucose metabolism is required for oocyte maturation of zebrafish. Biochemical and Biophysical Research Communications, 559, 191–196. https://doi.org/10.1016/j.bbrc.2021.04.059
  42. Khangembam, B. K., Yvr, K. S., & Chakrabarti, R. (2012). Purification and characterization of trypsin from the digestive system of carp Catla catla (Hamilton). International Aquatic Research, 4(1), 9. https://doi.org/10.1186/2008-6970-4-9
  43. Kharkan, J., Sayadi, M. H., Hajiani, M., Rezaei, M. R., & Savabieasfahani, M. (2023). Toxicity of nickel oxide nanoparticle in Capoeta fusca, using bioaccumulation, depuration, and histopathological changes. Global Journal of Environmental Science and Management, 9(3), 427–444. https://doi.org/10.22035/gjesm.2023.03.05
  44. Kombat, E. O., Abakari, G., Salifu, A.-R., Alhassan, E. H., & Zhao, J.-L. (2024). Proteolytic enzyme activity and mRNA expressions of amino acid and peptide transporter genes in tissues of Nile tilapia (Oreochromis niloticus) exposed to different salinities. Aquaculture, Fish and Fisheries, 4, e70024. https://doi.org/://doi.org/10.1002/aff2.70024
  45. Koracevic, D., Koracevic, G., Djordjevic, V., Andrejevic, S., & Cosic, V. (2001). Method for the measurement of antioxidant activity in human fluids. Journal of Clinical Pathology, 54(5), 356–361. https://doi.org/10.1136/jcp.54.5.356
  46. Kruger, N. J. (2009). The Bradford method for protein quantitation. In J. M. Walker (Ed.), The Protein Protocols Handbook. Springer Protocols Handbooks. (pp. 17–21). Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-198-7_4
  47. Kumar, N., Thorat, S. T., Gite, A., & Patole, P. B. (2023). Synergistic effect of nickel and temperature on gene expression, multiple stress markers, and depuration: an acute toxicity in fish. Environmental Science and Pollution Research, 30, 123729–123750. https://doi.org/10.1007/s11356-023-30996-6
  48. Lee, J., Jeon, M. J., Won, E.-J., Yoo, J.-w., & Lee, Y.-M. (2023). Effect of heavy metals on the energy metabolism in the brackish water flea Diaphanosoma celebensis. Ecotoxicology and Environmental Safety, 262, 115189. https://doi.org/10.1016/j.ecoenv.2023.115189
  49. Liu, C. Z., He, A.Y., Ning, L. J., Luo, Y., Li, D. L., Zhang, M. L., Chen, L. Q., & Du, Z. Y. (2018). Leptin selectively regulates nutrients metabolism in Nile tilapia fed on high carbohydrate or high fat diet. Frontiers in Endocrinology, 9, 574. https://doi.org/10.3389/fendo.2018.00574
  50. Liu, P., Liu, Y., Cheng, J., Xia, Y., & Yang, Y. (2024). Copper exposure causes alteration in the intestinal microbiota and metabolites in Takifugu rubripes. Ecotoxicology and Environmental Safety, 272, 116064. https://doi.org/10.1016/j.ecoenv.2024.116064
  51. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
  52. Lourenço, S., Neves, M., Gonçalves, E. M., Roseiro, C., Pombo, A., Raimundo, D., & Pinheiro, J. (2025). Application of fruit and vegetable processing by-products as ingredients in aquafeed. Discovery Food, 5, 45. https://doi.org/10.1007/s44187-025-00309-6
  53. Majid, S., Smeets, K., Vergauwen, L., Pilehvar, A., Knapen, D., & Blust, R. (2025). Insights into the combined toxicity of copper and cadmium in zebrafish (Danio rerio) embryos and adults. Ecotoxicology and Environmental Safety, 299, 118368. https://doi.org/10.1016/j.ecoenv.2025.118368
  54. Malhotra, N., Ger, T. R., Uapipatanakul, B., Huang, J. C., Chen, K. H. C., & Hsiao, C. D. (2020). Review of copper and copper nanoparticle toxicity in fish. Nanomaterials, 10(6), 1126. https://doi.org/10.3390/nano10061126
  55. Manivannan, A., Lee, E. S., Han, K., Lee, H. E., & Kim, D. S. (2020). Versatile nutraceutical potentials of watermelon – a modest fruit loaded with pharmaceutically valuable phytochemicals. Molecules, 25(22), 5258. https://doi.org/10.3390/molecules25225258
  56. Mebane, C., Schmidt, T., Miller, J., & Balistrieri, L. (2020). Bioaccumulation and toxicity of cadmium, copper, nickel, and zinc and their mixtures to aquatic insect communities. Environmental Toxicology and Chemistry, 39(4), 812–833. https://doi.org/10.1002/etc.4663
  57. Michael, O. S., Bamidele, O., Ogheneovo, P., Ariyo, T. A., Adedayo, L. D., Oluranti, O. I., Soladoye, E. O., Adetunji, C. O., & Awobajo, F. O. (2021). Watermelon rind ethanol extract exhibits hepato-renal protection against lead induced-impaired antioxidant defenses in male Wistar rats. Current Research in Physiology, 4, 252–259. https://doi.org/10.1016/j.crphys.2021.11.002
  58. Morariu, F. E., Zoican, E. C., Horablaga, M. N., Popa, N. F., Cristina, R. T., Dumitrescu, E., Grigorescu, C. C., Horablaga, A., & Morariu, S. (2025). Environmental trace metals contamination near a copper mining area from central-west region of Romania. Journal of Trace Elements in Medicine and Biology, 92, 127780. https://doi.org/10.1016/j.jtemb.2025.127780
  59. Muneeb, M., Alawam, A. S., Batool, S., Saif, N., Arif, A., Fatima, A., Fatima, M., Ahmad, S., Rudayni, H. A., Allam, A. A., Abbas, K. S., & Alagawany, M. (2026). Nutritional and functional feed additives in fishes: A comprehensive review. Aquaculture Reports, 48, 103615. https://doi.org/10.1016/j.aqrep.2026.103615
  60. Mushtaq, M., Sultana, B., Bhatti, H. N., & Asghar, M. (2015). RSM based optimized enzyme-assisted extraction of antioxidant phenolics from underutilized watermelon (Citrullus lanatus Thunb.) rind. Journal of Food Science and Technology, 52(8), 5048–5056. https://doi.org/10.1007/s13197-014-1562-9
  61. Mustafa, S. A., Al-Rudainy, A. J., & Salman, N. M. (2024). Effect of environmental pollutants on fish health: An overview. Egyptian Journal of Aquatic Research, 50(2), 225–233. https://doi.org/10.1016/j.ejar.2024.02.006
  62. Nahar, N., Fatema, U., Sharma, P., Bhuiya, A., Begum, T., Azahar, N., Rahman, M., Wan, S. W., & Azad, A. (2024). Antioxidant, anti-inflammatory, antidiabetic, anthelminthic and thrombolytic activity of the methanol extract of Citrullus lanatus peel. Universal Journal of Pharmaceutical Research, 9(2), 7–14. https://doi.org/0.22270/ujpr.v9i2.1085
  63. Narwal, N., Zahid, A., & Mian, A. K. (2025). Ecotoxicological effects of emerging pollutants (nanomaterials and microplastics) on fish biology. Animal Reproduction, 1(1), 60–74. https://doi.org/10.64636/ar.11
  64. Naz, S., Chatha, A. M., Téllez-Isaías, G., Ullah, S., Ullah, Q., Khan, M. Z., Shah, M. K., Abbas, G., Kiran, A., Mushtaq, R., Ahmad, B., & Kari, Z. A. (2023). A comprehensive review on metallic trace elements toxicity in fishes and potential remedial measures. Water, 15(16), 3017. https://doi.org/10.3390/w15163017
  65. Neiffer, D. L., & Stamper, M. A. (2009). Fish sedation, anesthesia, analgesia, and euthanasia: considerations, methods, and types of drugs. ILAR Journal, 50(4), 343–360. https://doi.org/10.1093/ilar.50.4.343
  66. Nishikimi, M., Rao, N. A., & Yagi, K. (1972). The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochemical and Biophysical Research Communications, 46(2), 849–854. https://doi.org/10.1016/S0006-291X(72)80218-3
  67. NRC (2011). Nutrient Requirements of Fish and Shrimp. The National Academies Press. https://nap.nationalacademies.org/catalog/13039/nutrient-requirements-of-fish-and-shrimp.
  68. Nys, C., Middleton, E., Garman, E., Schlekat, C., Van Sprang, P., & De Schamphelaere, K. (2025). Development of a bioavailability-based acute effects assessment method for nickel. Environmental Toxicology and Chemistry, 44(3), 841–855. https://doi.org/10.1093/etojnl/vgae071
  69. Ohga, H., Ito, K., Kakino, K., Mon, H., Kusakabe, T., Lee, J. M., & Matsuyama, M. (2021). Leptin is an important endocrine player that directly activates gonadotropic cells in teleost fish, chub mackerel. Cells, 10(12), 3505. https://doi.org/10.3390/cells10123505
  70. Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358. https://doi.org/10.1016/0003-2697(79)90738-3
  71. Oladimeji, T. E., Oyedemi, M. O., Odunfa, M. K., Agboola, O., Adeoye, J. B., Oke, M. A., & Akindele, O. O. (2025). From origin to oversight: properties, impacts and management of heavy metals. Discovery Applied Sciences, 7, 1353. https://doi.org/10.1007/s42452-025-07880-8
  72. Onyango, C., Nyairo, W., Tchieta, G. P., & Shikuku, V. O. (2025). Watermelon rind based adsorbents for the removal of water pollutants: a critical review. Frontiers in Environmental Chemistry, 6, 1568695. https://doi.org/10.3389/fenvc.2025.1568695
  73. Orozco, Z. G., Soma, S., Kaneko, T., & Watanabe, S. (2017). Effects of fasting and refeeding on gene expression of slc15a1a, a gene encoding an oligopeptide transporter (PepT1), in the intestine of Mozambique tilapia. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 203, 76–83. https://doi.org/10.1016/j.cbpb.2016.09.006
  74. Paglia, D. E., & Valentine, W. N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Medicine, 70(1), 158–169.
  75. Pavione, P. M., & Val, A. L. (2025). Interactive effect of copper and nickel on juveniles of tambaqui (Colossoma macropomum) exposed to pH 4 and pH 7. Journal of Trace Elements and Minerals, 13, 100257. https://doi.org/10.1016/j.jtemin.2025.100257
  76. Picó, C., Palou, M., Pomar, C., Rodríguez, A., & Palou, A. (2022). Leptin as a key regulator of the adipose organ. Reviews in Endocrine and Metabolic Disorders, 23(1), 13–30. https://doi.org/10.1007/s11154-021-09687-5
  77. Priastomo, M., Adlia, A., Rohayati, Lumbantobing, V., Widayat, W., Bahri, S., & Adnyana, K. (2025). Citrulline and arginine quantification in watermelon rind and anti-inflammatory potential using in silico analysis. Research Journal of Pharmacy and Technology, 18(10), 4849–4846. https://doi.org/10.52711/0974-360X.2025.00699
  78. Rahman, H., Priyanka, P., Lavanya, T., Srilakshmi, N., & Kumar, P. R. (2013). A review on ethnobotany, phytochemistry and pharmacology of Citrullus lanatus L. International Research Journal of Pharmacy and Applied Sciences, 3(3), 77–81.
  79. Reddy, N. A., Lakshmipathy, R., & Sarada, N. C. (2014). Application of Citrullus lanatus rind as biosorbent for removal of trivalent chromium from aqueous solution. Alexandria Engineering Journal, 53(4), 969–975. https://doi.org/10.1016/j.aej.2014.07.006
  80. Rezagholizade-Shirvan, A., Shokri, S., Dadpour, S. M., & Amiryousefi, M. R. (2023). Evaluation of physicochemical, antioxidant, antibacterial activity, and sensory properties of watermelon rind candy. Heliyon, 9(6), e17300. https://doi.org/10.1016/j.heliyon.2023.e17300
  81. Rico, X., Gullón, B., Alonso, J. L., & Yáñez, R. (2020). Recovery of high value-added compounds from pineapple, melon, watermelon and pumpkin processing by-products: an overview. Food Research International, 132, 109086. https://doi.org/10.1016/j.foodres.2020.109086
  82. Salnikow, K., Gao, M., Voitkun, V., Huang, X., & Costa, M. (1994). Altered oxidative stress responses in nickel-resistant mammalian cells. Cancer Research, 54, 6407–6412.
  83. Shahjahan, M., Taslima, K., Rahman, M., Al-Emran, M., Alam, S., & Faggio, C. (2022). Effects of heavy metals on fish physiology – a review. Chemosphere, 300, 134519. https://doi.org/10.1016/j.chemosphere.2022.134519
  84. Sheethal, K. U., Nadoor, P., Somashekara, S. R., Suryawanshi, U. A., Amogha, K. R., Telvekar, P. A., Shelke, S. T., & Pathan, J. G. K. (2024). Physiological changes in nickel-exposed Nile tilapia Oreochromis niloticus during exposure and recovery periods. Journal of Science Research and Reports, 30, 333–340. https://doi.org/10.9734/jsrr/2024/v30i62048
  85. Shokr, E. A. M. (2020). Effect of copper on hematological, biochemical changes and reproductive hormones of the Nile tilapia Oreochromis niloticus. Egyptian Journal of Aquatic Biology and Fisheries, 24(2), 1–18. https://doi.org/10.21608/ejabf.2020.76626
  86. Smii, H., Leite, C., Pereira, E., Soares, A. M. V. M., Beyrem, H., Dellali, M., & Freitas, R. (2025). Interactive effects of titanium-based compounds with gadolinium and mercury in Mytilus galloprovincialis. Aquatic Toxicology, 267, 106803. https://doi.org/10.1016/j.aquatox.2025.107494
  87. Sreedevi, P., Sivaramakrishna, B., Suresh, A., & Radhakrishnaiah, K. (1992). Effect of nickel on some aspects of protein metabolism in the gill and kidney of the freshwater fish, Cyprinus carpio L. Environmental Pollution, 77(1), 59–63. https://doi.org/10.1016/0269-7491(92)90158-7
  88. Suvarna, S. K., Layton, C., & Bancroft, J. D. (2018). Bancroft’s Theory and Practice of Histological Techniques (8th ed.). Churchill Livingstone, Elsevier.
  89. Tarazona-Díaz, M. P., Viegas, J., Moldao-Martins, M., & Aguayo, E. (2011). Bioactive compounds from flesh and by-product of fresh-cut watermelon cultivars. Journal of the Science of Food and Agriculture, 91(5), 805–812. https://doi.org/10.1002/jsfa.4250.
  90. Taslima, K., Al-Emran, M., Rahman, M. S., Hasan, J., Ferdous, Z., Rohani, M. F., & Shahjahan, M. (2022). Impacts of heavy metals on early development, growth and reproduction of fish – A review. Toxicology Reports, 9, 858–868. https://doi.org/10.1016/j.toxrep.2022.04.013
  91. Timpano, A. J., Jones, J. W., Beaty, B., Hull, M., Soucek, D. J., & Zipper, C. E. (2022). Combined effects of copper, nickel, and zinc on growth of a freshwater mussel (Villosa iris) in an environmentally relevant context. Aquatic Toxicology, 242, 106038. https://doi.org/10.1016/j.aquatox.2021.106038
  92. Vacca, F., Gomes, A. S., Murashita, K., Cinquetti, R., Roseti, C., Barca, A., Rønnestad, I., Verri, T., & Bossi, E. (2022). Functional characterization of Atlantic salmon (Salmo salar L.) PepT2 transporters. The Journal of Physiology, 600(10), 2377–2400. https://doi.org/10.1113/JP282781
  93. Vahdat, S., Noori, F., Van Stappen, G., & Agh, N. (2026). Effects of agricultural products, algae, and probiotics in a dry feed on growth performance, survival, immune response, biochemical indices, and reproductive traits of Artemia parthenogenetica. Aquaculture Reports, 46, 103342. https://doi.org/10.1016/j.aqrep.2025.103342
  94. Vijayan, L., Arumugam, M., Palaniyappan, S., Jayaraman, S., Brown, P. B., Kari, Z. A., Abdel-Warith, A.-W. A., Younis, E. M., & Ramasamy, T. (2024). Utilization of sustainable agri-waste watermelon rind for fishmeal in Labeo rohita diets: Effects on nutritional indices, hemato-biochemical properties, histoarchitechtural traits, amino acid and fatty acid profiles. Aquaculture Reports, 36, 102045. https://doi.org/10.1016/j.aqrep.2024.102045
  95. Wang, L., Hu, C., Wang, B., Wang, H., Wang, C., Shu, Y., Gao, C., & Yan, Y. (2023). Chronic environmentally relevant concentration of copper exposure induces intestinal oxidative stress, inflammation, and microbiota disturbance in freshwater grouper (Acrossocheilus fasciatus). Aquatic Toxicology, 263, 106702. https://doi.org/10.1016/j.aquatox.2023.106702.
  96. Wang, Z., Yeung, K. W. Y., Zhou, G.-J., Yung, M. M. N., Schlekat, C. E., Garman, E. R., Gissi, F., Stauber, J. L., Middleton, E. T., Lin Wang, Y. Y., & Leung, K. M. Y. (2020). Acute and chronic toxicity of nickel on freshwater and marine tropical aquatic organisms. Ecotoxicology and Environmental Safety, 206, 111373. https://doi.org/10.1016/j.ecoenv.2020.111373
  97. Wei, Y., Liu, X., Huang, J., Chen, H., He, Y., Chen, Y., & Lin, S. (2025). Effect of dietary quercetin supplementation on high-starch diet-induced growth impairment, metabolic dysregulation, and oxidative stress in largemouth bass (Micropterus salmoides). Aquaculture Reports, 41, 102704. https://doi.org/10.1016/j.aqrep.2025.102704
  98. Wilson, F., Cummings, T., Barbosa, T., Williams, C., Gerard, P., & Peebles, E. (2018). Comparison of two methods for determination of intestinal villus to crypt ratios and documentation of early age-associated ratio changes in broiler chickens. Poultry Science, 97(5), 1757–1761. https://doi.org/10.3382/ps/pex349
  99. Worthington, V. (1993). Worthington Enzyme Manual: Enzymes and Related Biochemicals. Worthington Biochemical Corporation, Freehold, NJ, USA.
  100. Wu, P., Xu, X., & Yu, T. (2021). Dietary watermelon residue influencing the nonspecific immunity of juvenile Pseudorasbora parva. Fish and Shellfish Immunology, 118, 421–425. https://doi.org/10.1016/j.fsi.2021.08.007
  101. Wu, X.-q., Li, M.-z., Lu, L., Chen, X.-m., Niu, X.-t., Kong, Y.-d., Wang, G.-q., Xia, C.-g., & Li, M. (2026). Copper mediates oxidative stress and immune response in snakehead (Channa argus) through Nrf2 and NF-κB pathway. Fish and Shellfish Immunology, 168, 110928. https://doi.org/10.1016/j.fsi.2025.110928
  102. Xie, D., Li, Y., Liu, Z., & Chen, Q. (2019). Inhibitory effect of cadmium exposure on digestive activity, antioxidant capacity and immune defense in the intestine of yellow catfish (Pelteobagrus fulvidraco). Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 222, 65–73. https://doi.org/10.1016/j.cbpc.2019.04.012
  103. Yin, B., Wang, X., Liu, Y., Fang, J., & Wang, W.-X. (2025). How fish intestinal cells responded to dietary methylmercury exposure? A single-cell transcriptomic analysis. Environmental Pollution, 371, 125967. https://doi.org/10.1016/j.envpol.2025.125967
  104. Zebral, Y. D., Anni, I. S. A., Afonso, S. B., Abril, S. I. M., Klein, R. D., & Bianchini, A. (2018). Effects of life-time exposure to waterborne copper on the somatotropic axis of the viviparous fish Poecilia vivipara. Chemosphere, 203, 410–417. https://doi.org/10.1016/j.chemosphere.2018.03.202
  105. Zhang, Z., Li, X., Zou, G., & Liang, H. (2023). Molecular characterization and response of silver carp (Hypophthalmichthys molitrix) GLUT1 under hypoxia stress. Fishes, 8(8), 425. https://doi.org/10.3390/fishes8080425
  106. Zhou, X., Liao, J., Lei, Z., Yao, H., Zhao, L., Yang, C., Zu, Y., & Zhao, Y. (2025). Nickel-based nanomaterials: a comprehensive analysis of risk assessment, toxicity mechanisms, and future strategies for health risk prevention. Journal of Nanobiotechnology, 23, 211. https://doi.org/10.1186/s12951-025-03248-7
DOI: https://doi.org/10.2478/aoas-2027-0023 | Journal eISSN: 2300-8733 (formerly 1642-3402) | Journal ISSN: 1642-3402
Language: English
Submitted on: Mar 3, 2026
Accepted on: Aug 25, 2026
Published on: Nov 3, 2026
Published by: National Research Institute of Animal Production
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Related subjects:

© 2026 Afaf N. Abdel Rahman, Asmaa Yaseen, Abdallah Tageldein Mansour, Mohamed Ashour, Roshmon Thomas Mathew, Hesham A. Hassanien, Ahmed Abbas, Tarek Khamis, Rowida E. Ibrahim, Sara T. Elazab, published by National Research Institute of Animal Production
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.