Research Article

Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats

Volume: 42 Number: 2 June 30, 2025

Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats

Abstract

Ketoconazole (KZ) is a broad-spectrum antifungal drug that can cause hepatotoxicity. Curcumin (CM), an isolate of Curcuma longa L. is used in folk medicine to treat various ailments. This study assessed whether CM can protect against a rat model of KZ-induced hepatotoxicity. Thirty healthy adult Wistar rats (220-240g) were randomly grouped (n=5/group) and supplemented orally with CM (50, 100 and 200 mg/kg/day) prior to the oral administration of KZ (200 mg/kg/day) for 14 days. On day 15, the rats were weighed and anesthetized. Blood samples were collected, and sera were extracted for biochemical analyses. Liver samples were excised, weighed and processed for oxidative stress markers and histology. KZ significantly (p < 0.01) decreased body weight and significantly (p< 0.001) decreased liver glutathione, superoxide dismutase, catalase, and glutathione peroxidase levels when compared to control. KZ significantly (p < 0.01) increased liver weight and significantly (p < 0.001) increased serum gamma-glutamyl transferase, alkaline phosphatase, amino transferases, lactate dehydrogenase, total bilirubin and liver malondialdehyde levels when compared to control. KZ caused hepatocyte necrosis. However, CM supplementation significantly restored body and liver weights at 50 mg/kg (p < 0.05), 100 mg/kg (p < 0.01) and 200 mg/kg (p < 0.01) when compared to KZ. CM supplementation restored serum biochemical and liver oxidative stress markers at 50 mg/kg (p < 0.05), 100 mg/kg (p < 0.01) and 200 mg/kg (p < 0.001) when compared to KZ. CM restored liver histology. CM was effective against KZ-induced hepatotoxicity in a dose-related fashion.

Keywords

Ethical Statement

The European Communities Council Directive of 24 November 1986 (86/609/EEC) was carefully and vividly followed during the course of this study as stated in the methodology section.

Thanks

Thanks for the privilege give to us to submit our research work.

References

  1. Zhou ZX, Yin XD, Zhang Y, Shao QH, Mao XY, Hu WJ, S.et al. Antifungal Drugs and Drug-Induced Liver Injury: A Real-World Study Leveraging the FDA Adverse Event Reporting System Database. Front. Pharmacol. 2022; 13:891336.
  2. Khoza S, Moyo I, Ncube D. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats. J Toxicol. 2017;2017:6746989.
  3. Ying YJ, Xiao Lu N, Mei TQ, Yan ZS, Yan De Z. Ketoconazole Associated Hepatotoxicity: A Systematic Review and Meta-analysis. Biomed Environ Sci, 2013; 26(7): 605-610
  4. Greenblatt HK, Greenblatt DJ. Liver Injury Associated with Ketoconazole: Review of the Published Evidence. The J Clin Pharmacol 2014; 54(12) 1321–1329
  5. Mahmoud Bothina L, Ahmad El-roghy, Eman S, Kefafy, Maisa A et al. Light and electron microscopic study on the effect of ketoconazole on the liver of adult male albino rats. Menoufia Med J, 2016; 29 (4), 21. 929-35.
  6. Farzaei MH, Zobeiri M, Parvizi F, El-Senduny FF, Marmouzi L, Coy-Barrera E et al. Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective. Nutrients. 2018; 10(7): 855. 1-28
  7. Liu S, Liu J, He L, Liu L, Cheng B, Zhou F, Cao D, He Y. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. Mole. 2022; 27(14):4400.
  8. Monfared AL, Yousefizadeh Y. Curcumin ameliorates sertraline-mediated testicular toxicity in rats via inhibition of oxidative stress Iranian J Toxiciol, 2023; 17 (1)25-34.

Details

Primary Language

English

Subjects

Gastroenterology and Hepatology

Journal Section

Research Article

Publication Date

June 30, 2025

Submission Date

August 28, 2024

Acceptance Date

April 16, 2025

Published in Issue

Year 2025 Volume: 42 Number: 2

APA
Similoluwa, B., Ebong, N., & Similoluwa, B. (2025). Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats. Deneysel Ve Klinik Tıp Dergisi, 42(2), 133-138. https://izlik.org/JA95UH85KC
AMA
1.Similoluwa B, Ebong N, Similoluwa B. Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats. J. Exp. Clin. Med. 2025;42(2):133-138. https://izlik.org/JA95UH85KC
Chicago
Similoluwa, Bamiwuye, Nwakaego Ebong, and Bamiwuye Similoluwa. 2025. “Curcumin Protects Against Ketoconazole-Induced Hepatotoxicity in Wistar Rats”. Deneysel Ve Klinik Tıp Dergisi 42 (2): 133-38. https://izlik.org/JA95UH85KC.
EndNote
Similoluwa B, Ebong N, Similoluwa B (June 1, 2025) Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats. Deneysel ve Klinik Tıp Dergisi 42 2 133–138.
IEEE
[1]B. Similoluwa, N. Ebong, and B. Similoluwa, “Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats”, J. Exp. Clin. Med., vol. 42, no. 2, pp. 133–138, June 2025, [Online]. Available: https://izlik.org/JA95UH85KC
ISNAD
Similoluwa, Bamiwuye - Ebong, Nwakaego - Similoluwa, Bamiwuye. “Curcumin Protects Against Ketoconazole-Induced Hepatotoxicity in Wistar Rats”. Deneysel ve Klinik Tıp Dergisi 42/2 (June 1, 2025): 133-138. https://izlik.org/JA95UH85KC.
JAMA
1.Similoluwa B, Ebong N, Similoluwa B. Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats. J. Exp. Clin. Med. 2025;42:133–138.
MLA
Similoluwa, Bamiwuye, et al. “Curcumin Protects Against Ketoconazole-Induced Hepatotoxicity in Wistar Rats”. Deneysel Ve Klinik Tıp Dergisi, vol. 42, no. 2, June 2025, pp. 133-8, https://izlik.org/JA95UH85KC.
Vancouver
1.Bamiwuye Similoluwa, Nwakaego Ebong, Bamiwuye Similoluwa. Curcumin protects against ketoconazole-induced hepatotoxicity in Wistar rats. J. Exp. Clin. Med. [Internet]. 2025 Jun. 1;42(2):133-8. Available from: https://izlik.org/JA95UH85KC