Melatonin enhanced the restoration of biochemical profile in chlorambucil treated-rats: examination of after-withdrawal effects of the drug

Abstract

Background: In the wake of global prevalence of different types of cancer, the widespread use of chemotherapy poses threat to the integrity of the reproductive system. Although chlorambucil (Chrm) has anti-calcinogenic action, its administration has been associated with reproductive damage. Similar to chlorambucil, melatonin has anti-cancerous effect. Moreover, the hormone is claimed to protect the reproductive tissues from the insult of different disruptors of their functionality and histoarchitecture. Therefore, the present study investigated the effects of post-administration of melatonin in Chrm treated rats, with an interest in examining the after-withdrawal effects of the drug.

Methods: Forty rats of ten animals per group were used for the study which lasted for six weeks. The control group received normal saline (vehicle; 0.1 ml/day, p.o.) for six weeks, while group 2 was administered saline for three weeks and then Chrm during the subsequent three weeks. However, in groups 3 and 4, Chrm was administered during the first three weeks; thereafter, they were administered saline and melatonin respectively during the subsequent three weeks. Chrm and melatonin were administered at 0.2 and 10 mg/kg b.w./day (p.o.) respectively.

Results: The administration of Chrm significantly decreased gonadotrophin releasing hormone, follicle stimulating hormone, luteinising hormone, testosterone and antioxidant enzymes, but significantly elevated pro-oxidant and pro-inflammatory markers compared to the control group. Moreover, it was accompanied with selected significant alterations of semen parameters and lipid indices. However, restoration of baseline status of testosterone, catalase, total antioxidant capacity, malondialdehyde, lactate dehydrogenase, uric acid, sperm count, and free fatty acid was simply enhanced by the withdrawal of the drug, while that of gonadotrophin releasing hormone, testosterone, semen parameters, superoxide dismutase, catalase, c-reactive protein, lactate dehydrogenase, and high density lipoprotein cholesterol was facilitated by the administration of melatonin.

Conclusion: The restoration of biochemical profile after chlorambucil treatment could be enhanced by the administration of melatonin.

Keywords: chlorambucil; melatonin; reproduction; toxicity