engleski

Alleviation of irinotecan toxicity by HI-6 oxime: in vivo study focused on ChE/AChE activity

Acetylcholinesterase (AChE) is an extremely active enzyme necessary for terminating the action of acetylcholine (ACh) in cholinergic synapses. There are many natural and synthetic compounds that inhibit the AChE followed by accumulation of acetylcholine and a generalised cholinergic crisis. Irinotecan is one of frequently used antineoplastic drugs, which has shown remarkable antitumor activity. In spite of beneficial outcomes, the majority of this drug also exhibit side effects that imply the use of special supportive care. The mechanism of action of HI-6 oxime as a therapeutic component with protection/ reactivation of the inhibited AChE is clear at this time. In the present study, we investigated its effect in vivo on the rats when given as pre-treatment and therapy in combination with the same drug. Both HI-6 and irinotecan act as inhibitors of ChE/AChE activity, but show different level of inhibition of ChE in plasma and AChE in liver and brain tissue. Our results indicate that the sequence of administration of HI-6 significantly affected the measured enzyme activity. In rats given HI-6 as therapy the enzyme activity was lower that in those that received HI-6 as pre-treatment. It is possible that when HI-6 given 15 minutes before irinotecan, it had enough time to reach the target and temporarily occupy the enzyme making it unavailable for irinotecan. Hi-6 relieves the cholinergic side effects and possesses acceptable toxicity profile, which might significantly improve the response to therapy. However, further studies are essential.

irinotecan; HI-6; ChE; AChE

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