Evaluation of the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine

Hamideh Khakshour 1, Behnam Ahmadnezhad 2, *, Mostafa Shalikar 3, Pejman Mortazavi 4 and Mitra Aghazadeh 5

1 Faculty of Pharmacy, Mazandaran University of Medical Sciences, Ramsar Campus.
2 Department of Pharmacology, Faculty of Veterinary Sciences, Islamic Azad University, Research Sciences Branch, Tehran, Iran.
3 Department of basic sciences, Faculty of Veterinary Sciences, Islamic Azad University, Research Sciences Branch, Tehran, Iran.
4 Department of Pathology, Faculty of Veterinary Sciences, Islamic Azad University, Research Sciences Branch, Tehran, Iran.
5 Faculty of histological Veterinary Sciences, Islamic Azad University, Research Sciences Branch, Tehran, Iran.
 
Research Article
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 297–303.
Article DOI: 10.30574/gscbps.2022.19.1.0157
Publication history: 
Received on 17 March 2022; revised on 23 April 2022; accepted on 25 April 2022
 
Abstract: 
Melatonin is an endocrine hormone, produced by the pineal gland from the amino acid tryptophan. Melatonin level in the body according to a predetermined cycle and are affected by light received. Gemcitabine is an anti-cancer drug. The mechanism of action of gemcitabine affects the properties of the cellular phase and mainly destroys the cells that are making DNA (phase-s). Nephrotoxic side effects of gemcitabine have been reported in patients receiving this drug medication. Melatonin is a potent free radical scavenger and antioxidant and has protective effects against ischemic damage. The aim of the present study was to investigate the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine and to evaluate the effects of different doses of melatonin on the protection of adult liver cells treated with gemcitabine. This experimental study was performed on male Wistar rats weighing approximately 250±20g and aged 8 weeks. Mice were randomly divided into 3 main groups. The first group (G1); the control group, received only normal saline. The second group (G2); the treated groups, divided into 2 subgroups T1 and T2, This group received melatonin at doses of 10 and 20 mg/kg and intraperitoneal (IP) with gemcitabine at a dose of 50 mg/kg, respectively. The third group (G3); negative control group, divided into 3 subgroups T3, T4 and T5. Subgroup T3, gemcitabine at 50 mg/kg, and T4 and T5, they received melatonin at doses of 10 and 20 mg/kg, intraperitoneally (IP) respectively. The number of mice in each group was 6 mice.
The results obtained from the injection of gemcitabine in groups clearly showed the side and cytotoxic effects in the liver tissue that the most lesions were observed in the subgroup (T3). In the groups receiving melatonin, the amount of these lesions was significantly reduced and the reduction of injuries was directly related to the dose of melatonin. The results of this study show that melatonin is effective in reducing the side effects of gemcitabine.
 
Keywords: 
Gemcitabine; Melatonin; Fat Degeneration; Chemotherapy; Inflammation
 
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