Combined effects of carbon tetrachloride and chlordecone on calmodulin activity in gerbil brain

Abstract

The potentiation of carbon tetrachloride (CCl4) toxicity by chlordecone (CD) pretreatment in different animal models is well established. However, these studies have only dealt with hepatotoxicity. The present study was initiated to determine whether CD preexposure potentiates CCl4 neurotoxicity in gerbils. Gerbils were chosen for the reason that the metabolism of CD in gerbil is similar to that of humans. Gerbils (50-80 g), fed on diet without or with CD (10 ppm) for 15 d, were challenged with a single dose of CCl4 (15 microliters, ip). Ca(2+)-ATPase and calmodulin (CaM) activities were determined in gerbil brain P2 fraction and cytosol, respectively, at intervals of 0.5, 2, 6, 12, and 24 h after CCl4 administration. Ca(2+)-ATPase and CaM activities were decreased at 0.5 and 2 h in both CD-preexposed and CCl4-treated gerbils. However, CaM activity returned to normal levels after 6 h and Ca(2+)-ATPase activity showed 80% recovery after 2 h. In vitro experiments showed that CCl4 alone at 5 microM concentration inhibited Ca(2+)-ATPase activity up to 50%. Combination of CD (0.5 microM) and CCl4 (1 and 5 microM) on Ca(2+)-ATPase activity showed no additive effect in vitro. Interaction between CCl4 and CaM was studied in the presence and absence of CD by monitoring NPN fluorescence. The decrease in NPN fluorescence observed with CCl4 was not potentiated by CD preincubation. These data suggest that CD does not enhance CCl4-induced alterations of Ca(2+)-ATPase and CaM activities in gerbil brain.