Showing papers by "Martin J. J. Ronis published in 1995"

Phenethyl isothiocyanate, a new dietary liver aldehyde dehydrogenase inhibitor.

Abstract: Phenethyl isothiocyanate (PEITC) is found in cabbages and other commonly ingested cruciferous vegetables. Isothiocyanates have anticarcinogenic properties, proposed to be mediated in part by their inhibition of several cytochrome P450 (CYP) forms. We administered PEITC to rats treated chronically with ethanol for 38 days by means of total enteral nutrition model to inhibit CYP2E1. We observed that PEITC not only efficiently prevented the ethanol-induced elevation of CYP2E1 apoprotein and mRNA, but also significantly elevated blood acetaldehyde levels. An elevation also was observed in naive animals acutely administered PEITC and ethanol, an effect found to be associated with marked inhibition of liver aldehyde dehydrogenase (ALDH). PEITC (1 mmol/kg) inhibited total liver ALDH activity by more than 70% and inhibition persisted for at least 24 hr. The inhibition was similar to that caused by an equimolar dose of disulfiram. Experiments using subcellular rat liver fractions revealed that both low- and high-Km ALDH forms were inhibited by low concentrations of PEITC (IC50 = 0.8-6.0 microM). Importantly, the mitochondrial low-Km ALDH activity, which is mainly responsible for detoxification of low aldehyde levels, was strongly inhibited (IC50 = 1.4 microM). In contrast, neither alcohol dehydrogenase nor lactate dehydrogenase activity was inhibited by PEITC. Thus, PEITC inhibits liver ALDH with a potency similar to that of disulfiram, suggesting that, in susceptible individuals, ingestion of large amounts of cruciferous vegetables in combination with alcohol could give rise to antabus-like symptoms. This property of PEITC must be taken into account in experimental alcohol research and in evaluating its proposed anticarcinogenic actions on chemical procarcinogens that are activated into potentially carcinogenic aldehydes.

Effects of 2‐methylisoborneol (MIB), and ethanol on the expression and activity of cytochrome P450s from the channel catfish

Abstract: Injection of 1 mg kg−1 of 2-methylisoborneol (MIB) caused an increase in a CYP1A-like protein of approximately 56 kDa from the kidneys of juvenile channel catfish as determined by western blot analysis using antibodies raised against trout CYP1A1 Ethoxyresorufin O-deethylase activity from kidneys of MIB-injected fish was significantly elevated as compared to ethanol-injected controls Static exposure of juvenile channel catfish to 10 ppm MIB caused a statistically significant induction of a CYP2K-like protein of approximately 53 kDa from the livers of treated catfish as determined by western blot analysis using antibodies raised against trout CYP2K1 Treatment of juvenile channel catfish with ethanol (1 ml kg−1) reduced the expression of one kidney and two constitutive liver P450s, while increasing another kidney form There was no difference in carbon tetrachloride-induced lipid peroxidation in livers after ethanol treatment Thus, MIB and ethanol affect the expression of at least three P450 isoforms in channel catfish tissues