[Ca++ ion transport blockers as reversants of the drug resistance of malarial parasites. 2. The effect of praziquantel on the resistance to chloroquine and compound R-70-Zh of Plasmodium berghei]. / Blokatory transporta ionov Ca++ kak reversanty lekarstvennoi ustoichivosti maliariinykh parazitov. Soobshchenie 2. Vliianie prazikvantelia na ustoichivost' k khlorokhinu i soedineniiu R-70-Zh u Plasmodium berghei.

The reversing action of anthelminthic praziquantel (P) on the effect of chloroquine (C) and compound R-70-Zh (styrylquinazoline) was revealed on a Plasmodium berghei model (white inbred mice), using a LNK65 isolate with naturally reduced sensitivity to chloroquine and its polyresistant line LNK65CHLFR with acquired resistance to chloroquine/fansidar (selected in our laboratory). P (125 mg/kg) in combination with C showed a potentiating effect not only on the LNK65 isolate, but also on the LNK65CHLFR line, while investigated separately on this line, both drugs were not effective in tested doses. Moreover, the similar effect of C on the LNK65CHLFR line was achieved in the dose that was 4 times higher than that of P/C combination. P in a standard dose on the LNK65 isolate showed a more marked activation of compound R-70-Zh that on C. The potentiating effect was manifested in combination with R-70-Zh in the dose half as high as that of C; this phenomenon was also reflected by the efficiency index (5.0 against the 4.0) accepted in our laboratory and may be associated with the higher sensitivity of the LNK65 isolate to R-70-Zh. P showed some antimalarial action which manifested itself only by morphological changes on P. berghei parasites similar to those observed under the action of some dihydropholate reductase inhibitors, such as pyrimethamine.

The role of glutathione in the toxicity of styrene.

The role of glutathione in the toxicity of styrene has been proposed based on the observations that glutathione inhibits the covalent binding of styrene and styrene oxide in vitro and that the administration of these compounds to animals decreases the glutathione content in the liver in vivo. In this study methionine (a precursor of reduced glutathione) or diethylmaleate (a depletor or reduced glutathione) was administered to hamsters concomitantly with styrene. Methionine protected the liver against the hepatotoxicity of styrene as indicated by the serum alanine aminotransferase activity. Diethylmaleate potentiated the hepatotoxic effect of styrene. A threshold value for hepatic glutathione of about 1 mmol/l was found for styrene toxicity. Cell damage occurred when the concentration of reduced glutathione in the liver has a central role in the development of cell damage caused by styrene.