16-Substituted steroids alleviate LPS-induced neurodegenerative disorders in rats

The neuroprotective effects of some 16-substituted steroidal derivatives against the locomotive impairment and cognitive deficits in the lipopolysaccharide (LPS)-induced neuroinflammation model of rats have been investigated. The in vivo and in vitro evaluations include behavioural tests (actophotometer, block tests, Morris water maize and elevated plus maize), estimation of the biochemical parameters such as acetylcholinesterase, lipid peroxide, reactive oxygen, and nitric oxide species and molecular assays for the key proinflammatory mediators like Tumour Necrosis Factor alpha (TNF-α) and Interleukin 1 beta (IL- 1β) after 21 days of the treatment with the steroids. Behavioural and biochemical studies indicated impairment in the locomotor activity and cognitive dysfunction in rats after LPS treatment. In addition, higher levels of TNF-α and IL-1β in the blood serum of the rats were also noticed. However, significant alleviation of LPS-induced movement and memory disorders was observed in LPS-injected rats after treatment with 16-substituted steroidal derivatives 1-11. Furthermore the biochemical and molecular studies revealed suppression of oxidative and nitrosative stress, decreased acetylcholinesterase activity, and reduction of TNF-α and IL-1β levels after treatment with compounds 1-11. Among all the 16-substituted steroidal derivatives, the compounds 8 and 11 were found to be the most active neuroprotective agents and produced effects marginally better than standard drug dexamethasone.