Melatonin alleviates cisplatin induced liver toxicity in rats by up-regulation of Nrf2/HO-1 signaling pathway

Mohamed, Soha M.Y.; Khodir, Suzan A; Abd El-aziz, Noha; Zaki, Nader G; Abdel-Fattah, Heba G; Abdelmalak, Marian F. L.; Slima, Shireen Ragab; Elkhouli, Ekbal; Adawi, Mai; A.Abdellatif, Hidi A.; Bayomi, Asmaa I; abdel wahab, Safaa Mohamed

doi:10.21608/muj.2025.410105.1250

	Melatonin alleviates cisplatin induced liver toxicity in rats by up-regulation of Nrf2/HO-1 signaling pathway
Medicine Updates
Articles in Press, Accepted Manuscript, Available Online from 30 August 2025
Document Type: Original Article
DOI: 10.21608/muj.2025.410105.1250
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Authors
Soha M.Y. Mohamed¹; Suzan A Khodir ²; Noha Abd El-aziz³; Nader G Zaki³; Heba G Abdel-Fattah⁴; Marian F. L. Abdelmalak⁵; Shireen Ragab Slima⁶; Ekbal Elkhouli⁷; Mai Adawi⁸; Hidi A. A.Abdellatif⁹; Asmaa I Bayomi¹⁰; Safaa Mohamed abdel wahab¹¹
¹Medical Physiology Department, Faculty of Medicine Ain Shams University, Cairo, Egypt. Medical Physiology Department, Faculty of Dentistry, Misr International University, Cairo, Egypt
²Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
³Anatomy and Embryology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
⁴Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
⁵Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
⁶Forensic medicine and Clinical Toxicology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
⁷Pathology Department, Faculty of medicine Mansoura University, Egypt
⁸Medical Physiology Department Department, Faculty of Medicine, Suez Canal University (SCU), Ismailia, Egypt
⁹Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University (SCU), Ismailia 41522, Egypt; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, King Salman International University,
¹⁰Zoology department, Faculty of Science, Menoufia University.
¹¹Medical Physiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Abstract
Background: One of the most well-known chemotherapy drugs is cisplatin (Cis). Hepatotoxicity is among the most significant adverse effects of cisplatin. The pineal gland hormone melatonin (Mel) is primarily reliant on the light/dark cycle for its cyclic release. This neurohormone can preserve tissue redox equilibrium and functions as an antioxidant. Aim: The purpose of the study was to assess hepatoprotective impact of Mel in rats exposed to Cis, as well as any possible underlying processes. Methods: Three groups of thirty adult male albino rats were created: control, Cis, and Cis+Mel. Hepatic MDA, hepatic SOD, hepatic TNF-α, hepatic IL-6, hepatic IL-10, liver-expressed Nrf2 and HO-1 genes and serum liver enzymes were measured. Additional assessments of the liver's caspase-3 and NF-kB immunoreaction were conducted. Results: Hepatic SOD, IL-10, and Nrf2 and HO-1 gene expression all significantly decline in response to cis-induced damage. Nevertheless, as compared to control, there was a notable rise in serum liver enzymes along with hepatic MDA, TNF-α, and IL-6, along with an upregulation of caspase-3 and NF-kB immunoreaction in the liver. Mel significantly improved the liver abnormalities brought on by Cis. Conclusion: Mel employed anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms in addition to up-regulating the Nrf2/HO-1 signaling cascade to reduce the hepatotoxicity brought on by Cis.
Keywords
Caspase-3. Cisplatin; Hepatotoxicity. HO-1; Melatonin. NF-kB; Nrf2


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