Ameliorative Effect of 80% Methanolic Cannabis sativa Leaf Extract on Copper (II) Oxide-Induced Alterations in Serum Electrolytes in Wistar Rats
Authors
Department of Veterinary Physiology and Biochemistry, Usmanu Danfodio University Sokoto (Nigeria)
Department of Veterinary Physiology and Biochemistry, Abubakar Tafawa Balewa University Bauchi (Nigeria)
Department of Veterinary Physiology and Biochemistry, Federal University of Agriculture Zuru (Nigeria)
Department of Veterinary Physiology and Biochemistry, Abubakar Tafawa Balewa University Bauchi (Nigeria)
Department of Veterinary Physiology and Biochemistry, Usmanu Danfodio University Sokoto (Nigeria)
Department of Veterinary Physiology and Biochemistry, Usmanu Danfodio University Sokoto (Nigeria)
Department of Veterinary Physiology and Biochemistry, Abubakar Tafawa Balewa University Bauchi (Nigeria)
Department of Veterinary Physiology and Biochemistry, Abubakar Tafawa Balewa University Bauchi (Nigeria)
Department of Veterinary Physiology and Biochemistry, Usmanu Danfodio University Sokoto (Nigeria)
Department of Veterinary Physiology and Biochemistry, Usmanu Danfodio University Sokoto (Nigeria)
Article Information
DOI: 10.51244/IJRSI.2026.1308000074
Subject Category: Biochemistry
Volume/Issue: 13/8 | Page No: 898-906
Publication Timeline
Submitted: 2026-08-22
Accepted: 2026-08-27
Published: 2026-09-04
Abstract
This study investigated the protective effect of 80% methanolic Cannabis sativa leaf extract against copper(II) oxide (CuO)-induced alterations in serum electrolyte balance in Wistar rats. Acute toxicity studies were conducted to determine the median lethal dose (LD₅₀) of the crude C. sativa leaf extract and CuO. The ameliorative effect of the extract on CuO-induced electrolyte disturbances was subsequently evaluated in vivo. The crude C. sativa leaf extract exhibited an LD₅₀ of 676.08 mg/kg, whereas CuO exhibited a markedly lower LD₅₀ of 45.71 mg/kg, indicating greater acute toxicity. Wistar rats were assigned to control and treatment groups and administered CuO followed by the crude C. sativa leaf extract. Serum samples were analyzed for sodium (Na⁺), potassium (K⁺), chloride (Cl⁻), and bicarbonate (HCO₃⁻), as well as selected biochemical parameters. CuO exposure produced significant alterations in serum electrolyte concentrations compared with the control group. Administration of the 80% methanolic C. sativa leaf extract following CuO exposure modulated these electrolyte alterations, with significant differences observed among treatment groups (P < 0.05). The findings suggest that CuO exposure disrupts electrolyte homeostasis, potentially through alterations in renal function and fluid balance. The observed modulatory effects of the extract indicate its potential to mitigate CuO-induced electrolyte disturbances. Thus, C. sativa leaf extract may represent a potential source of bioactive compounds for managing heavy-metal-induced toxicity and associated disturbances in electrolyte homeostasis. Further studies are required to identify the active constituents and elucidate the mechanisms underlying these effects.
Keywords
Cannabis sativa; copper (II) oxide; crude extract; electrolyte balance; LD₅₀; toxicity
Downloads
References
1. Dahiru, A., Nawaz, I., Riaz, S. K., Chaudry, S. S., Khan, M. J., Huang, Q., Abbas, M., & Eqani, S. A. M. A. S. (2026). Molecular mechanisms underlaying fluoride-induced neurotoxicity: interplay of antioxidants and endoplasmic reticulum stress–mediated apoptotic pathways in rats. Naunyn-Schmiedeberg’s Archives of Pharmacology. https://doi.org/10.1007/s00210-026-05441-3. [Google Scholar] [Crossref]
2. Enehizena, O. O., A. E. Mathias, S. E. I. Rogue, O. O. Festus, E. T. Moses, and W. O. Ohiwerei. 2026. “AMELIORATIVE AND PROTECTIVE EFFECTS OF ACTIVATED CHARCOAL ON SERUM TOTAL PROTEIN, ALBUMIN, GLOBULIN, AND WHITE BLOOD CELL COUNT IN CADMIUM-INDUCED WISTAR RATS.” Innovative Journal of Medical Sciences (ISSN: 2714-3325) 8(8): 29–46. [Google Scholar] [Crossref]
3. Shin, Eun-Joo, Ji Hoon Jeong, Yeonggwang Hwang, Naveen Sharma, Duy-Khanh Dang, Bao-Trong Nguyen, Seung-Yeol Nah, et al. 2021. “Methamphetamine-Induced Dopaminergic Neurotoxicity as a Model of Parkinson’s Disease.” Archives of Pharmacal Research 44(7): 668–88. doi:10.1007/s12272-021-01341-7. [Google Scholar] [Crossref]
4. Liu, Wu, Yan Xue, Chenyin Cao, Liting Yang, and Lijun Zhang. 2026. “Copper Homeostasis and Cuproptosis in Neurological Disorders.” Drug Design, Development and Therapy Volume 20: 1–32. doi:10.2147/DDDT.S580005. [Google Scholar] [Crossref]
5. Fatima, Ghizal, Sadaf Khan, Jan Fedacko, Ammar Mehdi Raza, Ram B. Singh, and Jaipaul Singh. 2026. “Trace Elements as Molecular Orchestrators of Health and Disease: A Biochemical and Pathophysiological Perspectives.” In Functional Biochemistry of Metallic Elements, eds. Naranjan S. Dhalla, Paramjit S. Tappia, and Anureet K. Shah. Cham: Springer Nature Switzerland, 19–42. doi:10.1007/978-3-032-14445-4_2. [Google Scholar] [Crossref]
6. Hial, Azher, Abdulhussein Ashour, Anwar Almzaiel, and Nashwan Jabbar. 2025. “Pathochemical and Clinical Chemistry Assessment of Biochemical Determinants Associated with Hemorrhagic Fever Patients Under Surgical and Anesthetic Management in Dhi Qar Province, Iraq.” Ibn Sina Journal of Medical Science Health & Pharmacy: 8. doi:10.64440/IBNSINA/SINA008. [Google Scholar] [Crossref]
7. R.M., KavyaDeepu, and Mohnish Sekar. 2025. “A Comprehensive Review of Electrolyte Imbalances and Their Applied Aspects in Dermatology.” Cureus. doi:10.7759/cureus.81353. [Google Scholar] [Crossref]
8. Wal, Ankita, Shweta Yadav, Kamal Deka, Bhagawati Saxena, Namra Aziz, Nardev Singh, Abida Khan, and Amin Gasmi. 2026. “Pharmacological Efficacy and Traditional Uses of Cannabis Sativa: A Comprehensive Review.” Current Organic Chemistry 30. doi:10.2174/0113852728395972251207093735. [Google Scholar] [Crossref]
9. Simankowicz, Paulina, and Joanna Stępniewska. 2025. “The Role of Endocannabinoids in Physiological Processes and Disease Pathology: A Comprehensive Review.” Journal of Clinical Medicine 14(8): 2851. doi:10.3390/jcm14082851. [Google Scholar] [Crossref]
10. Hassan, Ibrahim, Wan Norhamidah Wan Ibrahim, Ferdaus Mohamat Yusuf, Siti Aqlima Ahmad, and Syahida Ahmad. 2020. “Biochemical Constituent of Ginkgo Biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias Javanicus) Model.” Journal of Toxicology. doi:10.1155/2020/8815313. [Google Scholar] [Crossref]
11. Kwon, Hee Jung, Hyomin Lee, Sunyi Lee, Woori Ko, Shin Jea Yun, Yoshihiro Uesawa, and Joohee Jung. 2025. “Comparative Analysis of OECD Guideline Data and Tox21 Assays to Improve Reproductive and Developmental Toxicity Prediction.” Scientific Reports 16(1): 3417. doi:10.1038/s41598-025-33419-3. [Google Scholar] [Crossref]
12. Clemente, M., M. D. Miguel, K. B. Felipe, C. Gribner, P. F. Moura, A. G.R. Rigoni, L. C. Fernandes, et al. 2019. “Acute and Sub-Acute Oral Toxicity Studies of Standardized Extract of Nasturtium Officinale in Wistar Rats.” Regulatory Toxicology and Pharmacology. doi:10.1016/j.yrtph.2019.104443. [Google Scholar] [Crossref]
13. Adekola, M. B., J. O. Areola, N. O. Omisore, F. T. Asaolu, S. G. Ogunleye, O. E. Apalowo, and O. O. Babalola. 2020. “Sub-Chronic Toxicity Study of Ethanol Stem-Bark Extract of Blighia Sapida (Sapindaceae) in Wistar Rats.” Heliyon. doi:10.1016/j.heliyon.2019.e02801. [Google Scholar] [Crossref]
14. Patlolla, Anita K., and Paul B. Tchounwou. 2005. “Cytogenetic Evaluation of Arsenic Trioxide Toxicity in Sprague-Dawley Rats.” Mutation Research - Genetic Toxicology and Environmental Mutagenesis. doi:10.1016/j.mrgentox.2005.08.007. [Google Scholar] [Crossref]
15. Parasuraman, S., R. Raveendran, and R. Kesavan. 2010. “Blood Sample Collection in Small Laboratory Animals.” Journal of Pharmacology and Pharmacotherapeutics. doi:10.4103/0976-500X.72350. [Google Scholar] [Crossref]
16. Namiki, Yusuke, Kenji Ida, Yoko Homma, Namino Tomimori, Ken Sato, Chihaya Kakinuma, Hidehisa Tachiki, and Takuo Ogihara. 2026. “Investigation of the Effects of Calcium Alginate on Blood Sodium Concentration and the Suppression of Blood Pressure Elevation in Rats.” Biological and Pharmaceutical Bulletin 49(3): 564–71. doi:10.1248/bpb.b25-00592. [Google Scholar] [Crossref]
17. Kuo, Yuh-Chen, Vincent F. S. Tsai, Shih-Ping Liu, Jyh-Horng Chen, Hong-Chiang Chang, and Ju-Ton Hsieh. 2026. “Chloride-Dependent Mechanisms Contribute to Urinary Bladder Smooth Muscle Contractility: Pharmacological and Molecular Evidence from Rat Bladder Tissue.” Tzu Chi Medical Journal. doi:10.4103/tcmj.TCMJ-D-26-00143. [Google Scholar] [Crossref]
18. Mahmoud, ُEman Shaaban, Asmaa Tighian, Marwa Refaie, Mostafa Asem, Azza Abdel Zaher, Sayed Shehata, and Eman Mahmoud. 2025. “Packed RBCs versus Sodium Bicarbonate in the Treatment of Aluminum Phosphide-Induced Cardiotoxicity and Metabolic Acidosis in Rats.” Ain Shams Journal of Forensic Medicine and Clinical Toxicology 44(1): 48–56. doi:10.21608/ajfm.2025.337915.1151. [Google Scholar] [Crossref]
19. Al‐Thani, Najlaa A., Gavin S. Stewart, and Derek A. Costello. 2025. “The Role of the Urea Cycle in the Alzheimer’s Disease Brain.” Journal of Neurochemistry 169(3): e70033. doi:10.1111/jnc.70033. [Google Scholar] [Crossref]
20. Akamo, Adio J., Boluwatife A. Olagunju, Iyabode A. Kehinde, Naomi M. Akamo, Adetutu O. Ojelabi, Ofem E. Eteng, Ibiyemi O. Opowoye, et al. 2025. “Chemotherapeutic Efficacy of Curcumin against Plasma and Cardio-Hepatorenal Electrolyte Disruption in Dichlorvos-Challenged Rats via Augmentation of Na+/K+-ATPase and Ca2+/Mg2+-ATPase Activities.” Journal of Trace Elements and Minerals 12: 100248. doi:10.1016/j.jtemin.2025.100248. [Google Scholar] [Crossref]
21. Rafati Rahimzadeh, Mehrdad, Mehravar Rafati Rahimzadeh, Sohrab Kazemi, and Ali Akbar Moghadamnia. 2024. “Copper Poisoning with Emphasis on Its Clinical Manifestations and Treatment of Intoxication” ed. Annisa Utami Rauf. Advances in Public Health 2024: 1–12. doi:10.1155/2024/6001014. [Google Scholar] [Crossref]
22. Sehgal, Shelly, Sachin Gupta, and Manish Kumar Mishra. 2024. “Electrolytes and Acid-Base Disorders.” In Clinical Applications of Biomolecules in Disease Diagnosis, eds. Ram Lakhan Singh, Pankaj Singh, and Neelam Pathak. Singapore: Springer Nature Singapore, 155–75. doi:10.1007/978-981-97-4723-8_7. [Google Scholar] [Crossref]
23. Adele, B.O., G.T. Ojo, A.O. Ige, A.O. Odetola, I.E. Emediong, and E.O. Adewoye. 2023. “Toxic Copper Level Increases Erythrocyte Glycolytic Rate, Glutathione Production and Alters Electrolyte Balance in Male Wistar Rats.” Journal of Trace Elements in Medicine and Biology 79: 127231. doi:10.1016/j.jtemb.2023.127231. [Google Scholar] [Crossref]
24. Ye, Y., H. Yuan, H. Wang, P. Zhang, and Y. Zhang. 2025. “Effects of Nitrogen, Phosphorus, and Potassium on the Growth Physiology and Secondary Metabolites of Hemp (Cannabis Sativa L.) under NaHCO3 Stress.” Russian Journal of Plant Physiology 72(5): 152. doi:10.1134/S1021443724610772. [Google Scholar] [Crossref]
25. Alam, Waqas, Haroon Khan, and Imad Ahmad. 2022. “Acid-Base and Electrolyte Balance Regulations with Phytonutrients.” In The Role of Phytonutrients in Metabolic Disorders, Elsevier, 291–311. doi:10.1016/B978-0-12-824356-5.00003-5. [Google Scholar] [Crossref]
26. Wittczak, Andrzej, Maciej Ślot, and Agata Bielecka-Dabrowa. 2023. “The Importance of Optimal Hydration in Patients with Heart Failure—Not Always Too Much Fluid.” Biomedicines 11(10): 2684. doi:10.3390/biomedicines11102684. [Google Scholar] [Crossref]
27. Młynarska, Ewelina, Natalia Kustosik, Maja Mejza, Zuzanna Łysoń, Dawid Delebis, Jakub Orliński, Jacek Rysz, and Beata Franczyk. 2024. “Renal Outcomes and Other Adverse Effects of Cannabinoid Supplementation.” Nutrients 17(1): 59. doi:10.3390/nu17010059. [Google Scholar] [Crossref]
28. Mansouri, Katharina, Thierry Hanh, and Andreas Hahn. 2025. “Hydration Meets Regulation: Insights into Bicarbonate Mineral Water and Acid–Base Balance.” Nutrients 17(14): 2291. doi:10.3390/nu17142291. [Google Scholar] [Crossref]
29. Tohamy, Hossam G., Osama S. El Okle, Amira A. Goma, Mohamed M. Abdel-Daim, and Mustafa Shukry. 2022. “Hepatorenal Protective Effect of Nano-Curcumin against Nano‑copper Oxide-Mediated Toxicity in Rats: Behavioral Performance, Antioxidant, Anti-Inflammatory, Apoptosis, and Histopathology.” Life Sciences 292: 120296. doi:10.1016/j.lfs.2021.120296. [Google Scholar] [Crossref]
30. Ren, Xiya, Limei Zhao, Yajie Hao, Xiu Huang, Guangna Lv, and Xiaoshuang Zhou. 2025. “Copper-Instigated Modulatory Cell Mortality Mechanisms and Progress in Kidney Diseases.” Renal Failure 47(1): 2431142. doi:10.1080/0886022X.2024.2431142. [Google Scholar] [Crossref]
Metrics
Views & Downloads
Similar Articles
- In Silico Safety Evaluation of Local Spices Tea Used Against Human Metapneumovirus (HMPV)
- Assessment of Genotoxicity and Inflammation in the Brain Hippocampus of Lead-Induced Mice Treated With Diospyros Mespiliformis
- Determination of Polycyclic Aromatic Hydrocarbons and Total Petroleum Hydrocarbons in Crude Polluted Soil from Esaba, Ughelli South, Delta Nigeria
- Lipase Derived from Bacteria Isolated from The Seawater of Muara Badak, East Kalimantan
- "The Interplay Between Nutritional Deficiencies and Susceptibility to Mycotoxicosis: Implications for Public Health and Food Safety"