The Effects of Agomelatine on The Biochemical and Pathological Features of Cisplatin-Induced Peripheral Neuropathy: The First Experimental Study in Rats

Abstract

AIM: To evaluate the effects of agomelatine on the biochemical and pathological features of cisplatin-induced peripheral neuropathy.

MATERIAL and METHODS: This study included a total of 30 male Wistar albino rats that weighed 285-300 grams and were divided into three groups: healthy controls (HC, n=10); cisplatin group (CIS, n=10) and agomelatine plus cisplatin group (AC, n=10). The CIS group received only cisplatin (EbeweLiba, Turkey) at a dose of 2.5 mg/kg, whereas the AC group received both agomelatine (25 mg/kg, Les Laboratoires Servier, France) and cisplatin (2.5 mg/kg). The animals were sacrificed by thiopental anaesthesia (50 mg/kg, IE Ulagay, Turkey) and sciatic nerves were dissected. The sciatic nerve tissue was analysed for the levels of malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH) and superoxide dismutase (SOD) and was examined histopathologically.

RESULTS: The mean levels of MDA, MPO, tGSH and SOD were 34.90 +/- 13.83, 41.30 +/- 18.03, 15.40 +/- 6.06 and 48.60 +/- 18.19, respectively. MDA and MPO were significantly lower in the AC group than in the CIS group (p<0.001 for both). However, the anti-oxidative parameters tGSH and SOD were significantly higher in the AC group than in the CIS group (p<0.001 for both). Pathological examinations revealed swollen myelinated nerve fibres and evident myelin sheath degeneration in the CIS group; in the AC group, the myelin sheath degeneration was less and the blood vessels were normal.

CONCLUSION: Agomelatine decreased the oxidative status in an experimental rat model of cisplatin-induced peripheral neuropathy. Myelin sheath degeneration was less in the AC group than in the CIS group. To our knowledge, this was the first study that showed the positive effects of agomelatine on cisplatin-induced neuropathy in rats.