Ameliorative role of rolipram, PDE-4 inhibitor, against sodium arsenite-induced vascular dementia in rats.

Arsenic exposure to the population leads to serious health problems like neurotoxicity, nephrotoxicity, and cardiovascular abnormality. In the present study, the work has been commenced to discover the prospect of rolipram a phosphodiestrase-4 (PDE-4) inhibitor against sodium arsenite (SA)-induced vascular endothelial dysfunction (EnDF) leading to dementia in rats. Wistar rats were treated with SA (5 mg/kg body weight/day orally) for 44 days for induction of vascular EnDF and dementia. Learning and memory were evaluated using Morris water maze (MWM) test. Vascular EnDF was evaluated using aortic ring preparation. Various biochemical parameters were also evaluated like brain oxidative stress (viz. reduced glutathione and thiobarbituric acid reactive substances level), serum nitrite/nitrate activity, acetylcholinesterase activity, and inflammatory markers (viz. neutrophil infiltration in brain and myeloperoxidase). SA-treated rats showed poor performance in water maze trials indicating attenuated memory and ability to learn with significant rise (p < 0.05) in brain acetylcholinesterase activity, brain oxidative stress, neutrophil count, and significant decrease (p < 0.05) in serum nitrite/nitrate levels and vascular endothelial functions. Rolipram (PDE-4 inhibitor) treatment (0.03 mg/kg and 0.06 mg/kg body weight, intraperitoneally daily for 14 days) significantly improved memory and learning abilities, and restored various biochemical parameters and EnDF. It is concluded that PDE-4 modulator may be considered the prospective target for the treatment of SA-induced vascular EnDF and related dementia.