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

Abstract

The potentiation of carbon tetrachloride (CCI₄) toxicity by chlordecone (CD) pretreat‐ment 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 CCI₄ neurotoxicity in gerbils. Cerbils 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 CCI₄ (15 μl, ip). Ca²⁺‐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 CCI₄ administration. Ca²⁺‐ATPase and CaM activities were decreased at 0.5 and 2 h in both CD‐preexposed and CCI₄‐treated gerbils. However, CaM activity returned to normal levels after 6 h and Ca²⁺‐ATPase activity showed 80% recovery after 2 h. In vitro experiments showed that CCI₄ alone at 5 μM concentration inhibited Ca²⁺‐ATPase activity up to 50%. Combination of CD (0.5 μM) and CCI₄ (1 and 5 μM) on Ca²⁺‐ATPase activity showed no additive effect in vitro. Interaction between CCI₄ and CaM was studied in the presence and absence of CD by monitoring NPN fluorescence. The decrease in NPN fluorescence observed with CCI₄ was not potentiated by CD preincu‐bation. These data suggest that CD does not enhance CCI₄‐induced alterations of Ca²⁺‐ATPase and CaM activities in gerbil brain.