Effect of pomegranate peel extract on cadmium-induced brain toxicity in common carp (Cyprinus carpio); Histopathological evaluation

Document Type : Original Article

Authors
Hossein Jafarzadeh 1
Soodeh Alidadi 2
Davar Shahsavani 3
1 Graduated of Veterinary Medicine, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
2 Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad
3 Department of Food Hygiene and Aquaculture, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
10.22034/ijvcs.2026.14894.1091
Abstract
This research was conducted to investigate the protective effects of pomegranate peel extract on brain tissue in experimental cadmium poisoning in common carp. 150 common carp were randomly divided into 5 groups in triplicate and evaluated for four weeks. The control group did not receive cadmium, the cadmium group received 0.5 mg/L of cadmium chloride; the cadmium+1% extract group received 0.35 g of pomegranate peel extract (1% of food weight) in addition to 0.5 mg/L of cadmium chloride in water; the cadmium+2% extract group received 0.7 g of pomegranate peel extract (2% of food weight) in addition to cadmium; and the cadmium+4% extract group received 1.4 g of pomegranate peel extract (4% of food weight) in addition to cadmium equally in four meals. After the four-week treatment period, six fish from each group were randomly selected and tissue samples were taken from their brains, fixed in 10% neutral buffered formalin, and stained with hematoxylin and eosin. Histopathological changes observed in the brain tissue of the cadmium group included hyperemia, hemorrhage, degeneration and necrosis of neurons, edema and vacuolation, and gliosis. Different amounts of pomegranate peel extract, especially 2% and 4%, reduced changes, but only the cadmium+4% extract was significant compared to the cadmium group (p<0.05). In general, it can be concluded that 4% pomegranate peel extract has significant protective effects on brain tissue in experimental cadmium poisoning in common carp.
Keywords
Cadmium chloride
Pomegranate peel extract
Histopathology
Brain
Common carp
Subjects
1.  Afshan, S; Ali, S; Ameen, U.S; Farid, M; Bharwana, S.A; Hannan, F. and Ahmad, R; Effect of different heavy metal pollution on fish. Res. J. Chem. Environ. Sci; 2014; 2(1):74-79.
2.  Ahmadniaye Motlagh, H; Rokhnareh, Z; Safari, O. and Selahvarzi, Y; Growth performance and intestinal microbial changes of Carassius auratus in response to pomegranate (Punica granatum) peel extract‐supplemented diets. J. World Aquac. Soc; 2021; 52(4):820-828.
3.  Almeida, J; Diniz, Y; Marques, S; Faine, L; Ribas, B. and Burneiko, R; The use of the oxidative stress responses as biomarkers in Nile tilapia (Oreochromis niloticus) exposed to in vivo cadmium contamination. Environ. Int; 2002; 27(8):673-679.
4.  Al-Onazi, W.A; Ali, M.H.H. and Al-Garni, T; Using pomegranate peel and date pit activated carbon for the removal of cadmium and lead ions from aqueous solution. J. Chem; 2021; 2021:5514118.
5.  Al-Rawahi, A.S; Rahman, M.S; Guizani, N. and Essa, M.M; Chemical composition, water sorption isotherm, and phenolic contents in fresh and dried pomegranate peels. Dry. Technol; 2013; 31(3):257-263.
6.  Al-Sawafi, A.G.A; Wang, L. and Yan, Y; Cadmium accumulation and its histological effect on brain and skeletal muscle of zebrafish. J. Heavy Met. Toxicity Dis; 2017; 2:1.
7.  Amri, Z; Ghorbel, A; Turki, M; Akrout, F.M; Ayadi, F; Elfeki, A. and Hammami, M; Effect of pomegranate extracts on brain antioxidant markers and cholinesterase activity in high fat-high fructose diet induced obesity in rat model. BMC Complement. Altern. Med; 2017; 17(1):339.
8. Azeem, A.A; El Shahat, A. and Mounir, A.M; Studying the effect of gamma-irradiated pomegranate peels aqueous extract against lead toxicity in Wistar rats. Pak. J. Zool; 2019; 51(1):347-353.
9.  Banc, R; Rusu, M.E; Filip, L. and Popa, D.S; The impact of ellagitannins and their metabolites through gut microbiome on the gut health and brain wellness within the gut-brain axis. Foods; 2023; 12(2):270.
10. Bassiri-Jahromi, S; Punica granatum (Pomegranate) activity in health promotion and cancer prevention. Oncol. Rev; 2018; 12(1):345.
11. Chang, X; Li, H; Feng, J; Chen, Y; Nie, G. and Zhang, J; Effects of cadmium exposure on the composition and diversity of the intestinal microbial community of common carp (Cyprinus carpio L.). Ecotoxicol. Environ. Saf; 2019; 171:92-98.
12. Fadzil, N.I; Ahmad, S.A; Yasid, N.A; Sabullah, M.K; Daud, H.M; Khalid, A; Padrilah, S.N. and Shukor, M.Y; Characterisation of cholinesterase and histopathological features of brain of Clarias gariepinus following exposure to cadmium. J. Environ. Biol; 2019; 40:133-142.
13. Favorito, R; Chiarelli, G; Grimaldi, M.C; De Bonis, S. and Lancieri, M; Bioaccumulation of cadmium and its cytotoxic effect on zebrafish brain. Chem. Ecol; 2011; 27:39-46.
14. Ghazizadeh, A.A; Imani, M; Babaei, H. and Kheirandish R; The effect of homologous platelet rich plasma on histopathology of testicular tissue in rats affected by acute toxemia induced by cadmium chloride. Iran. J. Vet. Clin. Sci; 2024; 18(2):77-88.
15. Hamed, H.S. and Abdel-Tawwab, M; Dietary pomegranate (Punica granatum) peel mitigated the adverse effects of silver nanoparticles on the performance, haemato-biochemical, antioxidant, and immune responses of nile tilapia fingerlings. Aquaculture; 2021; 540:736742.
16. Jafari, S; Rahbarian, R. and Noghreie, M; Protective effect of pomegranate peel (Punica granatum) ethanolic extract on common carp (Cyprinus carpio) exposed to cadmium. Iran. Sci. Fish. J; 2023; 31(6):95-105.
17. Jafarzadeh, H; Shahsavani, D. and Alidadi, S; Protective effects of pomegranate peel extract on the gill, liver, and kidney in experimental cadmium poisoning in common carp (Cyprinus carpio). Iran. J. Vet. Sci. Technol; 2024; 16(2):35-43.
18. Kumar, P. and Singh, A; Cadmium toxicity in fish: an overview. GERF Bull. Biosci; 2010; 1(1):41-47.
19. Leiva, K.P; Rubio, J; Peralta, F. and Gonzales, G.F; Effect of Punica granatum (Pomegranate) on sperm production in male rats treated with lead acetate. Toxicol. Mech. Methods; 2011; 21(6):495-502.
20. Liu, J; Lu, W; Guo, Z.Y; Li Y.H. and Lv, W.F; Cadmium activated oxidative stress and endoplasmic reticulum stress pathway promote apoptosis in the common carp (Cyprinus carpio L.) brain. Fish Shellfish Immunol; 2025; 165:110538.
21. Magangana, T.P; Makunga, N.P; Fawole, O.A. and Opara, U.L.; Processing factors affecting the phytochemical and nutritional properties of pomegranate (Punica granatum L.) peel waste: a review. Molecules; 2020; 25(20):4690.
22. Nayeem, N; Asdaq, S.M.B; Salem, H. and AHEl-Alfqy, S; Gallic acid: A promising lead molecule for drug development. J. Appl. Pharm; 2016; 8(2):213-218.
23. Ojo, O.A; Rotimi, D.E; Ojo, A.B; Ogunlakin, A.D. and Ajiboye, B.O; Gallic acid abates cadmium chloride toxicity via alteration of neurotransmitters and modulation of inflammatory markers in Wistar rats. Sci. Rep; 2023; 13(1):1577.
24. Patnaik, B.B; Howrelia, H; Mathews, T. and Selvanayagam, M; Histopathology of gill, liver, muscle and brain of Cyprinus carpio communis L. exposed to sublethal concentration of lead and cadmium. Afr. J. Biotechnol; 2011; 10(57):12218-12223.
25. Rahbarian, R; Rajabiian, M; Ramshini, H. and Jafari, S.A; Investigation of the protective effect of pomegranate peel extract in inhibiting the oxidative damage caused by experimental cadmium poisoning in common carp. J. Fish; 2022; 75(1):99-109.
26. Romeo, F.V; Ballistreri, G; Fabroni, S; Pangallo, S; Nicosia, M.G; Schena, L. and Rapisarda, P; Chemical characterization of different sumac and pomegranate extracts effective against Botrytis cinerea rots. Molecules; 2015; 20(7):11941-11958.
27. Shafiei, F; Soofiani, N.M; Ebrahimi, E; Nematollahi, A. and Mohebbi, A; Effect of alcoholic extract of pomegranate peel (Punica granatum L.) on blood parameters of common carp (Cyprinus carpio) fingerling. J. Fish. Sci. Technol. (JFST); 2016; 5(2):59-72.
28. Singha, B; Singhb, J; Pal Kaurb, A. and Singh, N; Phenolic compounds as beneficial phytochemicals in pomegranate (Punica granatum L.) peel: a review. Food Chem; 2018; 261:75-86.
29. Soyer Sarıca, Z; Karabacak, M; Kanbur, M; Eraslan, G; Liman, B.C. and Tekeli, M.Y; Antioxidant effects of pomegranate seed oil against pentachlorophenol toxicity in rat tissues. Erciyes Üniv. Vet. Fak. Derg; 2018; 15(3):230-237.
30. Tian, J; Hu, J; Liu, D; Yin, J; Chen, M; Zhou, L. and Yin, H; Cadmium chloride-induced transgenerational neurotoxicity in zebrafish development. Environ. Toxicol. Pharmacol; 2021; 81:103545.
31. Topal, A; Atamanalp, M; Alak, G; Oruc, E; Kocaman, E.M. and Saglam, Y.S; Effect of humic acid on the brain tissue of brown trout treated with cadmium. Int. J. Fish. Aquat. Stud; 2014; 1(5):18-21.
32. Unsal, V; Dalkıran, T; Çiçek, M. and Kolukçu, E; The role of natural antioxidants against reactive oxygen species produced by cadmium toxicity: a review. Adv. Pharm. Bull; 2020; 10(2):184-202.
33. Valavanidis, A; Vlahogianni, T; Dassenakis, M. and Scoullos, M; Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutants. Ecotoxicol. Environ. Saf; 2006; 64(2):178-189.
34. Vanella, L; Di Giacomo, C; Acquaviva, R; Barbagallo, I; Cardile, V; Kim, D.H; Abraham, N.G. and Sorrenti, V; Apoptotic markers in a prostate cancer cell line: effect of ellagic acid. Oncol. Rep; 2013; 30(6):2804-2810.
35. Vivek, K.G; Abhishek, K; Nikhat, J.S. and Bechan, S; Rat brain acetyl cholinesterase as a biomarker of cadmium induced neurotoxicity. J. Toxicol; 2016; 1(1):555553.
36. Winiarska-Mieczan, A; Krusiński, R. and Kwiecień, M; Tannic acid influence on lead and cadmium accumulation in the hearts and lungs of rats. Adv. Clin. Exp. Med; 2013; 22(5):615-620.
37. Wolfe, K.L; Kang, X; He, X; Dong, M; Zhang, Q. and Liu, R.H; Cellular antioxidant activity of common fruits. J. Agric. Food Chem; 2008; 56:8418-8426.
38. Xing, H; Li, S; Wang, Z; Gao, X; Xu, S. and Wang, X; Histopathological changes and antioxidant response in brain and kidney of common carp exposed to atrazine and chlorpyrifos. Chemosphere; 2012; 88:377-383.
39. Zarezadeh Mehrizi, R.A; Emam-Djomeh, Z; Shahedi Bagh Khandan, M; Loni, E; Akhavan, H.R. and Biabani, J; Identification and quantification of anthocyanins in pomegranate peel extract. Iran. J. Food Sci. Technol; 2016; 12(49):31-40.
40. Zheng, J.L; Yuan, S.S; Wu, C.W. and Lv, Z.M; Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio). Aquat. Toxicol; 2016; 180:36-44.
Iranian Journal of Veterinary Clinical Sciences
Volume 19, Issue 2 - Serial Number 33
Fall and Winter 2025/2026
March 2026
Pages 37-46