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Research Article


Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats

Yos Adi Prakoso, Krestel Joy Viernes Isla, Agustina Dwi Wijayanti.


Abstract
Background:
Fermented Crescentia cujete L (SFC) is a potential alternative therapy for ischemic stroke. However, the effects of SFC on various organs, the immune system, antioxidant levels, and MDA still need to be better understood.

Aim:
This study aimed to analyze the effects of SFC in rat models through a 14-day repeated-dose oral toxicity study, focusing on histopathology, granulocyte-macrophage colony-stimulating factor (GM-CSF) levels, COX-2, antioxidants, and MDA.

Methods:
This study used 20 male Sprague Dawley rat models. Rats were divided into four groups: 0 mg/kg BW SFC, 50 mg/kg BW SFC, 500 mg/kg BW SFC, and 2000 mg/kg BW SFC. The therapy was administered orally and repeated once daily for 14 days. On day 15, the rats were euthanized, and samples were collected. The samples were tested against histopathology, enzyme-linked immunosorbent assay, antioxidant level, and MDA. The data were statistically analyzed.

Results:
The results indicated that SFC did not affect histopathology (p≥0.05), except for an increase in BALT activity in lung tissue and congestion in the stomach mucosa (p≤0.05). SFC did not influence the rats’ serum protein levels (p≥0.05), but it did increase the level of GM-CSF and decrease the level of COX-2 in the serum and various organs (p≤0.05). Additionally, SFC increased the activity of catalase, glutathione peroxidase, glutathione, superoxide dismutase, and total antioxidants while decreasing the MDA level at a dosage of 2000 mg/kg BW (p≤0.05).

Conclusion:
The 14-day repeated-dose oral toxicity study of SFC did not show severe histopathological changes; however, it increased GM-CSF and antioxidant levels, which suppressed COX-2 and MDA levels.

Key words: Antioxidant; COX-2; Fermented Crescentia cujete L; GM-CSF; Histopathology.


 
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How to Cite this Article
Pubmed Style

Prakoso YA, Isla KJV, Wijayanti AD. Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats. Open Vet. J.. 2025; 15(12): 6527-6540. doi:10.5455/OVJ.2025.v15.i12.37

Web Style

Prakoso YA, Isla KJV, Wijayanti AD. Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats. https://www.openveterinaryjournal.com/?mno=233334 [Access: December 31, 2025]. doi:10.5455/OVJ.2025.v15.i12.37

AMA (American Medical Association) Style

Prakoso YA, Isla KJV, Wijayanti AD. Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats. Open Vet. J.. 2025; 15(12): 6527-6540. doi:10.5455/OVJ.2025.v15.i12.37


Vancouver/ICMJE Style

Prakoso YA, Isla KJV, Wijayanti AD. Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats. Open Vet. J.. (2025), [cited December 31, 2025]; 15(12): 6527-6540. doi:10.5455/OVJ.2025.v15.i12.37


Harvard Style

Prakoso, Y. A., Isla, . K. J. V. & Wijayanti, . A. D. (2025) Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats. Open Vet. J., 15 (12), 6527-6540. doi:10.5455/OVJ.2025.v15.i12.37


Turabian Style

Prakoso, Yos Adi, Krestel Joy Viernes Isla, and Agustina Dwi Wijayanti. 2025. Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats. Open Veterinary Journal, 15 (12), 6527-6540. doi:10.5455/OVJ.2025.v15.i12.37


Chicago Style

Prakoso, Yos Adi, Krestel Joy Viernes Isla, and Agustina Dwi Wijayanti. "Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats." Open Veterinary Journal 15 (2025), 6527-6540. doi:10.5455/OVJ.2025.v15.i12.37


MLA (The Modern Language Association) Style

Prakoso, Yos Adi, Krestel Joy Viernes Isla, and Agustina Dwi Wijayanti. "Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats." Open Veterinary Journal 15.12 (2025), 6527-6540. Print. doi:10.5455/OVJ.2025.v15.i12.37


APA (American Psychological Association) Style

Prakoso, Y. A., Isla, . K. J. V. & Wijayanti, . A. D. (2025) Effects of repeated 14-day oral toxicity of fermented Crescentia cujete (L.) on histopathology, GM-CSF, COX-2, antioxidants, and MDA levels in male Sprague Dawley rats. Open Veterinary Journal, 15 (12), 6527-6540. doi:10.5455/OVJ.2025.v15.i12.37


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