Hepatic effects of repeated oral administration of diclofenac to hepatic cytochrome P450 reductase null (HRN™) and wild-type mice

Hepatic NADPH-cytochrome P450 oxidoreductase null (HRN?) mice exhibit normal hepatic and extrahepatic biotransformation enzyme activities when compared to wild-type (WT) mice, but express no functional hepatic cytochrome P450 activities. When incubated in vitro with [¹⁴C]-diclofenac, liver microsomes from WT mice exhibited extensive biotransformation to oxidative and glucuronide metabolites and covalent binding to proteins was also observed. In contrast, whereas glucuronide conjugates and a quinone-imine metabolite were formed when [¹⁴C]-diclofenac was incubated with HRN? mouse liver, only small quantities of P450-derived oxidative metabolites were produced in these samples and covalent binding to proteins was not observed. Livers from vehicle-treated HRN? mice exhibited enhanced lipid accumulation, bile duct proliferation, hepatocellular degeneration and necrosis and inflammatory cell infiltration, which were not present in livers from WT mice. Elevated liver-derived alanine aminotransferase, glutamate dehydrogenase and alkaline phosphatase activities were also observed in plasma from HRN? mice. When treated orally with diclofenac for 7 days, at 30 mg/kg/day, the severities of the abnormal liver histopathology and plasma liver enzyme findings in HRN? mice were reduced markedly. Oral diclofenac administration did not alter the liver histopathology or elevate plasma enzyme activities of WT mice. These findings indicate that HRN? mice are valuable for exploration of the role played by hepatic P450s in drug biotransformation, but poorly suited to investigations of drug-induced liver toxicity. Nevertheless, studies in HRN? mice could provide novel insights into the role played by inflammation in liver injury and may aid the evaluation of new strategies for its treatment.     

Prejudice and the Plate: Effects of Weight Bias in Nutrition Judgments

As millions of people turn to social media for health information, better understanding the factors that guide health-related judgments and perceptions in this context is imperative. We report on two Web experiments (n > 400 total) examining the power of society’s widespread weight bias and related stereotypes to influence nutrition judgments in social media spaces. In Experiment 1, meals were judged as lower in nutritional quality when the person who recommended them (the source) was depicted as obese rather than of normal weight, an effect mediated by stereotypic beliefs about the source as a generally unhealthy person. Experiment 2 replicated this effect, which—notably—remained significant when controlling for objective nutritional information (calories and fat content). Results highlight spillover effects of weight bias that extend beyond person perception to color impressions of objects (here, food) that are associated with stigmatized attributes. Implications for everyday nutrition judgments and public health are considered.