Effect of environmental contaminants on Beta cell function.

There is an increasing concern that chemicals in the environment are contributing to the global rise in the prevalence of type 2 diabetes (T2D). However, there is limited evidence for direct effects of these chemicals on beta cell function. Therefore, the goals of this study were (1) to test the hypothesis that environmental contaminants can directly affect beta cell function and (2) examine mechanistic pathways by which these contaminants could affect beta cell function.

Effects in rats of maternal exposure to raspberry leaf and its constituents on the activity of cytochrome p450 enzymes in the offspring.

The goal of our study was to determine whether maternal exposure to red raspberry leaf (RRL) and its constituents can permanently alter biotransformation of fluorogenic substrates by cytochrome P450 (CYP) in the livers of male and female offspring. Nulliparous female rats received vehicle, raspberry leaf, kaempferol, quercetin, or ellagic acid orally once breeding had been confirmed until parturition. Hepatic microsomes were prepared from animals at birth (postnatal day 1 [PND1]), weaning (PND21), PND65, and PND120 to determine the biotransformation of 8 fluorogenic substrates.

Human cytochrome P450 liability studies of trans-dihydronarciclasine: a readily available, potent, and selective cancer cell growth inhibitor.

The cytochrome P45O activities of the naturally occurring Amaryllidaceae alkaloid narciclasine (3), isolated from Narcissus pseudonarcissus, and synthetic derivative trans-dihydronarciclasine (5) are reported. While narciclasine was found to possess potent inhibitory activity to human CYP3A4, its dihydro analogue was inactive. This study revealed that the C1-C10b double bond is required for inhibition of this crucial metabolizing enzyme.

Effects of cytochrome P450 inhibitors on the biotransformation of fluorogenic substrates by adult male rat liver microsomes and cDNA-expressed rat cytochrome P450 isoforms.

We have evaluated the use of a panel of six fluorogenic cytochrome P450 (CYP) substrates as a potential tool for rapid screening for global changes in CYP activity in rats under different physiological conditions. The biotransformation of 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC), 7-benzyloxy-4-(trifluoromethyl)-coumarin, 7-benzyloxyquinoline, 3-cyano-7-ethoxycoumarin, 7-methoxy-4-(trifluoromethyl)-coumarin, and 7-ethoxy-4-trifluoromethyl-coumarin by microsomes from adult male rat liver were characterized, their sensitivities to 15 putative inhibitors were determined and compared to similar experiments using nine different complementary DNA (cDNA)-expressed rat CYPs. Inhibitory profiles of the substrates in microsomes were different from each other, with some overlap, suggesting that each substrate is to some extent biotransformed by a different CYP isoform.

Effect of maternal raspberry leaf consumption in rats on pregnancy outcome and the fertility of the female offspring.

Background: The use of herbal medicines by pregnant women is on the rise. However, there is limited information regarding the safety of these compounds during pregnancy. Therefore, the goal of this study was to explore the consequences of raspberry leaf use during gestation in Wistar rats.