FIG. 4.

In vitro inhibition of rat liver β-naphthoflavone-induced microsomal metabolism by a series of manganoporphyrins. β-Naphthoflavone-induced rat liver microsomes are incubated with increasing concentrations of manganoporphyrins and inhibition of methoxyresorufin O-dealkylase (MROD) activity is measured spectrofluorometrically. Data is presented as percent of MROD activity in the absence of manganoporphyrins. Control MROD activity is 55 ± 6 pmol/min/mg. Each value is performed in triplicate and data are presented as their mean ± SEM. The inhibitory concentrations of manganoporphyrins that decreased xenobiotic metabolism by 50% (IC₅₀) are determined by fitting a sigmoidal curve with variable slope to the data. The MnTEPyP⁵⁺ and MnTDMIP⁵⁺ cationic manganoporphyrins are potent inhibitors of rat liver β-naphthoflavone-induced microsomal metabolism while the cationic MnTDEIP⁵⁺ and the non-cationic MnTBAP manganoporphyrins are much less potent inhibitors.