Free radicals as reactive intermediates in tissue injury.

TLDR: This article will concentrate mainly on specific experiments involving Promethazine to make some general points about the hepatotoxicity of CCl4.

Abstract: My interest in free radicals as reactive intermediates, which are capable of initiating tissue injury, developed from studies with CCl4 in 1963. Whilst attempting to understand the mechanism of action of various substances that protect against certain aspects of the liver injury produced by CCl4 I was impressed by the fact that several of these ‘protective agents’ were free radical scavengers. One such ‘protective agent’ and free radical scavenger is the phenothiazine derivative Promethazine (or Phenergan) which had been reportedl in 1961 to decrease the liver necrosis resulting from CCl4 administration to rats. That observation by Rees and Spector was the stimulus for me to start a long-term investigation on liver protective substances; we have now accumulated data on the effectiveness (or not) of more than 60 free radical scavengers in relation to the liver disturbances caused by CCl4 in vivo and in vitro. In this article, however, I will concentrate mainly on specific experiments involving Promethazine to make some general points about the hepatotoxicity of CCl4.