6β-hydroxycortisol:a marker for hepatic enzyme inhibition by lead

Abstract

Lead(Pb) ion is known to inhibit cytochrome P-450 dependent hepatic microsomal activity.To measure inhibitory effects of Pb on hepatic enzyme activity 6βOHF excretion was determined in 11 children(age 2-9 yrs)with mild to moderate Pb intoxication(n1 renal function) prior to chelation therapy.6βOHF is formed by the hepatic cytochrome P-450 dependent mixed function oxidase system. Correlations were examined between 6βOHF and blood Pb, erythrocyte protoporphyrin (EP) and urinary Pb excretion after a CaNa2 EDTA provocative test.The CaNa2EDTA provocative test provides an accurate “chemical biopsy” of chelatable lead stores.6βOHF excretion in normal controls was 0.28±.03 mg/m2/24h.Excretion in Pb burdened children was reduced to 0.17±.02 mg/m2/24h;(p<.01).There was a highly significant correlation between 6βOHF and EP,(r=-0.7, p<.01) and 6βOHF and urinary Pb(r= -0.74,p<.01) but none between blood Pb and 6βOHF.17OH corticosteroid and free cortisol excretion were not different from normal controls and correlations between these cortisol metabolites and EP or urinary Pb were not significant.Conclusions:Children with undue Pb absorption may have decreased 6βOHF excretion.Since adrenal function is not impaired,reduced 6βOHF excretion may be secondary to inhibitory action of Pb ion on microsomal enzyme systems.6βOHF measurements provide a sensitive probe when evaluating inhibitory effects of foreign compounds on hepatic enzyme activity.