IN VIVO SAFETY ASSESSMENT OF CURCUMIN-ENCAPSULATED ZIF-8 AND ZIF-67 NANOCOMPOSITES: A TOXICITY STUDY

Main Article Content

Hafiz Muhammad Asif
Sehrish Rana Rajpoot
Khalil Ahmad
Muhammad Wasim Tasleem
Khalil Ahmad

Keywords

Curcumin, ZIF-8, ZIF-67, toxicolgy, In vivo

Abstract

Background: Curcumin, derived from the dried root rhizome of Curcuma longa, exhibits a spectrum of therapeutic effects, including antifungal, antibacterial, anti-inflammatory, antispasmodic, antioxidant, and antiarthritic properties. Despite these benefits, its low absorption limits its efficacy. Enhancing bioavailability through loading onto zeolitic metallic organic frameworks such as zeolitic imidazolate framework-8 (ZIF-8) and zeolitic imidazolate framework-67 (ZIF-67) presents a promising solution.


 


Objective: This study aimed to evaluate the acute toxicity of curcumin and its composites in male albino wistar rats.


 


Methods: Curcumin composites were synthesized using a solvothermal method. Male albino wistar rats were divided into seven groups (n=6/group) and administered curcumin, curcumin zeolitic imidazolate 8 (CZ8), and curcumin zeolitic imidazolate 67 (CZ67) at varying oral doses (30mg/kg, 60mg/kg) to experimental groups, and normal control group was treated with distilled water for 14 days. Throughout the study, body weight, behavior, and mortality were monitored. Blood and tissue samples were collected for analysis on the final day, with histopathological examination of vital organs (liver, kidney, spleen, brain, and heart) performed. Liver and kidney function tests, along with hematological parameters, were evaluated.


 


Results: No adverse effects or mortality were observed at the maximum dose of 60 mg/kg for either curcumin composite. Histopathological analysis revealed normal morphology in most organs at both doses. Slight alterations in liver tissue morphology were observed only at the 60mg/kg dose for CZ8 and CZ67. Liver and kidney function tests, and hematological parameters remained within normal ranges in all treatment groups.


Conclusion: Curcumin composites CZ8 and CZ67 demonstrated good biocompatibility and safety at doses up to 60mg/kg in this acute toxicity study.

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References

1. Abbas, M. W., Hussain, M., Qamar, M., Ali, S., Shafiq, Z., Wilairatana, P., & Mubarak, M. S. (2021). Antioxidant and anti-inflammatory effects of Peganum harmala extracts: An in vitro and in vivo study. Molecules, 26(19), 6084.
2. Benameur, T., Soleti, R., Panaro, M. A., La Torre, M. E., Monda, V., Messina, G., & Porro, C. (2021). Curcumin as prospective anti-aging natural compound: focus on brain. Molecules, 26(16), 4794.
3. Bieniek, A., Terzyk, A. P., Wiśniewski, M., Roszek, K., Kowalczyk, P., Sarkisov, L., . . . Kaneko, K. (2021). MOF materials as therapeutic agents, drug carriers, imaging agents and biosensors in cancer biomedicine: Recent advances and perspectives. Progress in Materials Science, 117, 100743.
4. Darvesh, A. S., Carroll, R. T., Bishayee, A., Novotny, N. A., Geldenhuys, W. J., & Van der Schyf, C. J. (2012). Curcumin and neurodegenerative diseases: a perspective. Expert opinion on investigational drugs, 21(8), 1123-1140.
5. Dehzad, M. J., Ghalandari, H., Nouri, M., & Askarpour, M. (2023). Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials. Cytokine, 164, 156144.
6. Deng, S., Yan, X., Xiong, P., Li, G., Ku, T., Liu, N., . . . Jiang, G. (2021). Nanoscale cobalt-based metal-organic framework impairs learning and memory ability without noticeable general toxicity: First in vivo evidence. Science of The Total Environment, 771, 145063.
7. Khezri, K., Saeedi, M., Mohammadamini, H., & Zakaryaei, A. S. (2021). A comprehensive review of the therapeutic potential of curcumin nanoformulations. Phytotherapy Research, 35(10), 5527-5563.
8. Kumari, S., Howlett, T. S., Ehrman, R. N., Koirala, S., Trashi, O., Trashi, I., . . . Gassensmith, J. J. (2023). In vivo biocompatibility of ZIF-8 for slow release via intranasal administration. Chemical Science, 14(21), 5774-5782.
9. Küpeli Akkol, E., Bardakcı, H., Yücel, Ç., Şeker Karatoprak, G., Karpuz, B., & Khan, H. (2022). A New Perspective on the Treatment of Alzheimer’s Disease and Sleep Deprivation-Related Consequences: Can Curcumin Help? Oxidative Medicine and Cellular Longevity, 2022.
10. Lan, S., Zhang, J., Li, X., Pan, L., Li, J., Wu, X., & Yang, S.-T. (2022). Low toxicity of metal-organic framework MOF-74 (Co) nano-particles in vitro and in vivo. Nanomaterials, 12(19), 3398.
11. Ma, Z., Wang, N., He, H., & Tang, X. (2019). Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application. Journal of Controlled Release, 316, 359-380.
12. Ng’uni, T., Klaasen, J. A., & Fielding, B. C. (2018). Acute toxicity studies of the South African medicinal plant Galenia africana. Toxicology reports, 5, 813-818.
13. Oghenejobo, M., & Bethel, O. (2017). Antibacterial evaluation, phytochemical screening and ascorbic acid assay of turmeric (Curcuma longa). MOJ Bioequiv Availab, 4(2), 00063.
14. Oghenejobo, M., Opajobi, O., Bethel, U. O., & Uzuegbu, U. (2022). Determination of Antibacterial Evaluation, Phytochemical Screening and Ascorbic Acid Assay of Turmeric (Curcuma longa). Challenges and Advances in Pharmaceutical Research, 1, 146-161.
15. Park, J.-S., Cho, E.-Y., Kim, Y.-S., Kwon, E., Han, K.-M., Ku, S.-Y., . . . Kang, B.-C. (2020). In vivo and in vitro safety evaluation of fermented Citrus sunki peel extract: acute and 90-day repeated oral toxicity studies with genotoxicity assessment. BMC complementary medicine and therapies, 20, 1-13.
16. Peng, Y., Ao, M., Dong, B., Jiang, Y., Yu, L., Chen, Z., . . . Xu, R. (2021). Anti-inflammatory effects of curcumin in the inflammatory diseases: Status, limitations and countermeasures. Drug design, development and therapy, 4503-4525.
17. Pillai, N. G., Archana, K., Rhee, K. Y., Park, S.-J., & Asif, A. (2019). In vitro antiproliferative study of curcumin loaded nano zeolitic imidazolate framework hybrid biomaterials on HeLa cells. Journal of Industrial and Engineering Chemistry, 79, 288-294.
18. Ravindran, F., Mhatre, A., Koroth, J., Narayan, S., & Choudhary, B. (2023). Curcumin modulates cell type-specific miRNA networks to induce cytotoxicity in ovarian cancer cells. Life Sciences, 334, 122224.
19. Sharifi-Rad, J., Rayess, Y. E., Rizk, A. A., Sadaka, C., Zgheib, R., Zam, W., . . . Zielińska, D. (2020). Turmeric and its major compound curcumin on health: bioactive effects and safety profiles for food, pharmaceutical, biotechnological and medicinal applications. Frontiers in pharmacology, 11, 1021.
20. Sun, Y., Zheng, L., Yang, Y., Qian, X., Fu, T., Li, X., . . . Tan, W. (2020). Metal–organic framework nanocarriers for drug delivery in biomedical applications. Nano-Micro Letters, 12, 1-29.

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