AN OXIDATIVE MECHANISM FOR THE INHIBITION OF IODOTHYRONINE 5 0 -MONODEIODINASE ACTIVITY BY LEAD NITRATE IN THE FISH, HETEROPNEUSTES FOSSILIS SHYAM SUNDER CHAURASIA and ANAND KAR Thyroid Research Unit, School of Life Sciences, D.A. University, Khandwa Road, Indore 452 001, India (Received 26 November 1996; accepted 5 May 1998) Abstract. An oxidative mechanism in the lead-induced inhibition of thyroid function with special reference to iodothyronine 5 0 -monodeiodinase (5 0 -ID) activity has been identified in the fish, Het- eropneustes fossilis. Lead treatment (2.5, 5.0 and 10.0 ppm of lead nitrate/day for 30 days) enhanced tissue lipid peroxidation (LPO) and decreased the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT). In addition, serum triiodothyronine (T 3 ) concentration and hepatic 5 0 -ID activity were markedly decreased by 10 ppm of lead nitrate. These findings support the view that higher concentrations of lead nitrate inhibit the extrathyroidal conversion of thyroxine (T 4 ) to T 3 . Moreover, oxidative stress from lead intoxication could be responsible for inhibiting 5 0 -ID activity. Keywords: antioxidant enzymes, fish, iodothyronine 5 0 -monodeiodinase, lead, lipid peroxidation, thyroid hormones 1. Introduction Lead is recognized as an ubiquitous environmental contaminant (Lockitch, 1993). In fishes, lead reduces both 131 I uptake by the thyroid (Katti and Sathyanesan, 1987) and the circulating thyroid hormone concentration (Spieler and Weber, 1991). Re- cently, we showed that hepatic 5 0 -monodeiodination of thyroxine (T 4 ) to triiodothy- ronine (T 3 ) is inhibited by lead (Chaurasia et al., 1996a). However, the mechanism for lead-induced inhibition of 5 0 -monodeiodination was not determined. Iodothyronine 5 0 -monodeiodinase (5 0 -ID) is an integral membrane-bound en- zyme (Toyoda et al., 1995). The most metabolically active thyroid hormone, T 3 , is predominantly produced in the extrathyroidal tissues by conversion from T 4 in the presence of 5 0 -ID enzyme (MacLatchy and Eales, 1992). Eales (1985) suggested that 5 0 -ID activity was an important control point for regulating thyroid hormone levels. Lipid peroxidation (LPO) occurs in biological membranes with potentially in- jurious consequences (Comporti, 1985) and, very often, heavy metal toxicity has been associated with this process (Skoczynska et al., 1993; Chaurasia et al., 1996b). Antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) usually help in maintaining cellular integrity by protecting against the deleterious Water, Air, and Soil Pollution 111: 417–423, 1999. © 1999 Kluwer Academic Publishers. Printed in the Netherlands.