Melatonin Prevents Cisplatin-Induced Cyto-Histopathological Damage in the Bone Marrow and Inner Ear.

Abstract

Introduction: Cisplatin is an effective chemotherapeutic drug. Its side effects, ototoxicity and genotoxicity, limit widespread application. Melatonin could reduce these toxic effects due to its antioxidant activity.

Objective: To determine the effect of melatonin against cisplatin-induced ototoxicity and genotoxicity in rats.

Methods: To assess ototoxicity, 33 rats were randomly divided into: group 1 (saline), group 2 (melatonin), group 3 (cisplatin + saline), and group 4 (cisplatin + melatonin). Groups 3 and 4 received a single dose of 10 mg/kg of cisplatin. Groups 2 and 4 received daily doses of 1 mg/kg of melatonin. The number of viable neurons and their average diameter in the spiral and vestibular ganglia were analyzed. In the stria vascularis and spiral ligament, the number of viable cells was evaluated. To assess genotoxicity, 12 animals were randomly divided into: group A (saline), group B (cisplatin + saline), and group C (cisplatin + melatonin). The rats in groups B and C received a single dose of 10 mg/kg of cisplatin. Group C received a single dose of 1 mg/kg of melatonin.

Results: The micronucleus count and percentage of polychromatic erythrocytes in the bone marrow of rat femurs were analyzed. The animals in group 3 presented a greater loss of cells than the animals in other groups regarding all cochlear structures evaluated. Furthermore, the diameters of neurons were smaller in the animals in group 3. Melatonin-treated rats presented a lower micronucleus count and a higher number of polychromatic erythrocytes than animals treated with cisplatin alone.

Conclusion: Melatonin reduces cisplatin-induced cyto-histopathological damage in the bone marrow and inner ear; therefore, it could be used as a tumor adjuvant treatment.