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The effects of avermectins on radiation-and dexamethasone-induced apoptosis of rat thymocytes have been studied. In particular, the properties of abamectin (avermectin B 1 ), ivermectin (22,23-dihydroavermectin B 1 , H 2 B 1 ) and aversectin C were examined. Aversectin C is a mixture of eight naturally occurring avermectins of the following composition: B 1 (42%), B 2 (22%), A 1 (13%) and A 2 (23%). This mixture is currently widely used as active ingredient in veterinary antiparasitic formulations produced by Pharmbiomed Co. Apoptosis was estimated by membrane damage, nuclear pycnosis (or chromatin condensation), DNA fragmentation and percentage of cells with subdiploid DNA. It was shown that aversectin C inhibits thymocyte apoptosis induced by both agents. The IC 50 dose was in the range of 0.1-0.3 µg/ml for aversectin C, whereas abamectin and ivermectin produced no effect up to 1 µg/ml. It is suggested that avermectins of the A series are responsible for the high anti-apoptotic activity exhibited by aversectin C. Thus, aversectin C is not only an effective antiparasitic drug but is also capable of exhibiting some other useful activities, e.g. a cytoprotective effect exerted on the mammalian immune cells. Avermectins, antiparasitic drugs, apoptosis, thymocytes, dexamethasone, gamma raysThe avermectins are a family of closely related 16-membered macrocyclic lactones produced by the fungus Streptomyces avermitilis. Nearly all the avermectins exhibit a broad spectrum of activity against nematode and arthropode parasites, with the B 1a compound being the most potent (Campbell 1989). Accordingly, it was used as active ingredient in commercial antiparasitic formulations. Until recently, there were basically two types of such avermectin-based active ingredients, i.e. ivermectin (consisting mainly of avermectin H 2 B 1a ) and abamectin (predominantly containing avermectin B 1a ). However, several years ago the Pharmbiomed Co. started manufacturing the veterinary and plant protection formulations based on a new active ingredient -aversectin C which is an intrinsic mixture of eight naturally occurring avermectins. Preliminary experiments demonstrated that aversectin C (presumably due to the presence of avermectins of both the A-and B-series) possesses some new useful features compared to ivermectin and abamectin, e.g. with the same high efficacy, the spectrum of activity is broader, level of residues is lower and, hence, the shorter withdrawal periods could be recommended (Simetsky et al. 1994;Berezkina et al. 1996). Furthermore, degradation of aversectin C in soil and water was found to be more effective compared to abamectin and ivermectin ( M o sin et al. 1998) and, hence, ecologically aversectin C is safer.

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.

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