Introduction:

Hepatotoxicity induced by cisplatin (CP), a widely-used chemotherapeutic agent, significantly hampers its therapeutic efficacy. Oxidative stress due to reactive oxygen and nitrogen species plays a critical role in CP-induced liver injury. Crocus sativus (saffron), known for its phenolic compounds and antioxidative properties, has shown potential hepatoprotective effects. To enhance bioavailability and therapeutic efficiency, the present study evaluates the efficacy of nanofiber-based delivery systems encapsulating phenolic compounds extracted from C. sativus petals.

Methods:

Phenolic-rich fractions (CPEF) were extracted from dried C. sativus petals using ethyl acetate solvent. These fractions were encapsulated within zein-based electrospun nanofibers (CPN) exhibiting optimal morphology, stability, and encapsulation efficiency (89.6%). Male Balb/c mice were administered CP intraperitoneally to induce hepatotoxicity, followed by dietary supplementation with either CPEF or CPN (100 mg GAE/kg mice body weight). Treatment continued for 30 days post-induction, and mice were evaluated for changes in weight, food intake, biochemical markers, antioxidant enzyme activities, lipid peroxidation, gene expression, and histopathological alterations.

Results:

Both CPEF and CPN treatments significantly improved mice weight gain and food intake compared to untreated, CP-exposed controls (p ≤ 0.05). CPN notably reduced liver enzyme levels (ALT, AST, ALP) and total bilirubin, while elevating antioxidant enzyme activities (GPx, SOD, CAT) more effectively than CPEF alone. Additionally, lipid peroxidation, assessed through MDA levels, decreased significantly following CPN treatment. Gene expression analysis indicated significant downregulation of inflammatory markers (iNOS, INF-γ) and upregulation of SOD expression with CPN administration. Histopathological examination confirmed that CPN markedly improved liver and kidney tissue integrity compared to controls and CPEF treatment.

Discussion:

The nanofiber-based encapsulation markedly enhanced the hepatoprotective potential of C. sativus phenolic compounds, likely due to improved bioavailability, controlled release, and heightened antioxidative activity. These findings underscore the therapeutic promise of nanofiber formulations in mitigating cisplatin-induced hepatotoxicity through oxidative stress modulation, inflammation reduction, and enhancement of antioxidant defense systems.

References:

Abd Rashid, N., Abd Halim, S. A. S., Teoh, S. L., Budin, S. B., Hussan, F., & Ridzuan, N. R. A. (2021). Alhumaydhi, F. A., Khan, I., Rauf, A., Qureshi, M. N., Aljohani, A. S., & Khan, S. A. (2021). Del Campo, A., Valenzuela, R., Videla, L. A., & Zúniga-Hernandez, ˜ J. (2023). Mykhailenko, O., Ivanauskas, L., Bezruk, I., Sidorenko, L., Lesyk, R., & Georgiyants, V. (2021). Schulte-Werning, L. V., Murugaiah, A., Singh, B., Johannessen, M., Engstad, R. E., Skalko-Basnet, ˇ N., & Holsæter, A. M. (2021). Shamansoori, M. T., Karimi, E., & Oskoueian, E. (2022). Singh, G., Haileselassie, Y., Ji, A. R., Maecker, H. T., Sinha, S. R., & Brim, H. (2022). Tajaddini, A., Roshanravan, N., Mobasseri, M., Aeinehchi, A., Sefid-Mooye Azar, P., Hadi, A., & Ostadrahimi, A. (2021). Videla, L. A., & Valenzuela, R. (2022).

Acknowledgments:

The authors are grateful to the Islamic Azad University of Mashhad and Arka Industrial Cluster, Mashhad, Iran.

Disclosure Information:

The authors declare no conflicts of interest.

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2025 International Conference on Biofabrication

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