Investıgatıon of protectıon of resveratrol agaınst cytosıne arabınosıde ınduced ocular and cerebellar toxıc effects ın experımental anımal models

Objectives: To evaluate the protective effect of resveratrol on Ara-C induced cerebellar and ocular toxicity.Methods: Twenty-eight female rats (Wistar) each weighing 250 gr, 10-12 weeks old were used and rats were divided into the four equal groups. Group 1: the control group, Group 2: 400 mg/ kg Ara-C, Group 3: 3 mg/ kg resveratrol, and Group 4 :400 mg/ kg Ara-C +3 mg/ kg resveratrol for 5 days. The right eyes of all the rats were treated with artificial tear drops 4 times daily, and the left eyes were tested as the control. All rats were sacrificed at day 5. To investigate the cerebellar toxicity of Ara-C and protection of resveratrol, immunohistochemical and biochemical examinations were performed at cerebellar tissue. In addition, to investigate the functions of cerebellum, Morris water maze test was performed during this study. To investigate the corneal toxicity due to Ara-C and protection of resverarol, corneal light microscopy were examined. In addition in order to investigate the oxidative damage associated with Ara-C, the serum levels of systemic oxidative stress markers and antioxidant enzymes were studied.Results In cerebellums of rats that Ara-C was given heavy and light chain isoforms of neurofilaments (NF) were significantly decreased. This reduction in isoforms of NF was prevented by resveratrol. In corneal examinations classic histopathologic findings due to Ara-C has not been demonstrated. The only finding detected in all groups ,except the control eyes of the control group, was the basement membrane irregularity. In rats treated with Ara-C, spatial learning and swimming rates did not affected; but spatial memory was found to be impaired. This effect was prevented by resveratrol significantly. In rats treated with Ara-C, among antioxidant enzymes the serum levels of catalase and cerebellum levels of gluthation peroxidase were reduced significantly. Resveratrol used in this dose did not effect the reduction of these two enzymes.Conclusion: In this in vivo model, we showed that Ara-C induced cerebellar neurofilament light and heavy chain reduction and changes in spatial memory can be significantly prevented by resveratrol. In this study the reason that we could not demonstrate the classic ocular toxicity of Ara-C may be the swimming of rats. Except the serum catalase and cerebellum GPx reduction oxidant injury at biochemical level has nat been shown. These findings suggest that resveratrol can be a good candidate to work as an antioxidant agent in order to avoid the toxicity of high dose Ara-C.Key words: Ara-C, cerebellar toxicity, corneal toxicity, neurofilament isoforms, resveratrol.