EFFECT OF LONG-TERM IRON-DEFICIENCY ON THE ACTIVITIES OF HEPATIC AND EXTRAHEPATIC DRUG-METABOLIZING-ENZYMES IN FISCHER RATS

Male Fischer rats were maintained for a period of 17 weeks on an iron- deficient diet along with suitable controls. The effect of long term d eprivation of iron on xenobiotic metabolism was studied by the activit ies of various drug metabolising enzymes in both liver as well as extr a-hepatic tissues like lungs, kidneys and intestinal mucosa (I.M.). Th e results show that among the Phase I (activating) enzymes, the hepati c activities of benzo(a)pyrene hydroxylase (AHH) and microsomal epoxid e hydrolase (mEH) are significantly reduced in iron deficiency. The ot her parameters of the activating system, namely cytochrome P450, amino pyrene demethylase (ADM) and aniline hydroxylase (AH), are not altered . Of the two Phase II (conjugating) enzymes studied, only uridine diph ospho glucuronyl transferase (UDPGT) is found to be depressed, but not glutathione S-transferase (GST) in liver in iron deficiency. Activiti es of Phase I enzymes are markedly lowered in extra-hepatic tissues co mpared to liver; such depression is not observed in conjugating enzyme s. Iron deficiency does not seem to make much impact on the enzyme act ivities of extra-hepatic tissues. Overall, the hepatic results suggest a defect in detoxification mechanisms in iron deficiency. Such impair ment may very well predispose an iron-deficient host to an increased r isk of carcinogenesis.