Metabolomic profiling for juvenile Chinook salmon exposed to contaminants of emerging concern.

Both targeted and non-targeted metabolomic analyses were conducted on juvenile ocean-type fall Chinook salmon (Oncorhynchus tshawytscha) residing in two estuaries receiving wastewater treatment plant (WWTP) effluent and one reference estuary. The data show that the metabolome patterns for fish from the two WWTP-receiving estuaries were more similar to each other compared to that for the reference site fish. Also, a comparison of the metabolome for fish from the reference site and fish from a hatchery upstream of one of the effluent-receiving estuaries indicated no differences, implying that residency for fish in the contaminated estuary resulted in major changes to the metabolome. Based on general health parameters including whole-body lipid content and condition factor, plus the availability of prey for these fish, we conclude that juvenile Chinook salmon in these contaminated estuaries may have been experiencing metabolic disruption without any overt signs of impairment. Additionally, a non-targeted analysis was performed on hatchery summer Chinook salmon from a laboratory study where fish were dosed for 32 days with feed containing 16 of the most common contaminants of emerging concern (CECs) detected in wild fish. In the laboratory experiment a relationship was observed between dose and the number of liver metabolites that were different between control and treatment fish. Laboratory fish were exposed to only 16 CECs, but are generally exposed to hundreds of these compounds in contaminated aquatic environments. These results have implications for the health of juvenile Chinook salmon and the likelihood of a successful life cycle when exposed to effluent-related chemicals.

The Impact of Proximal Roux-en-Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism.

BACKGROUND: Roux-en-Y gastric bypass (RYGBS), a surgery that creates a smaller stomach pouch and reduces the length of small intestine, is one of the most common medical interventions for the treatment of obesity. AIM: The aim of this study was to determine how RYGBS affects the absorption and metabolism of acetaminophen. MATERIALS AND METHODS: Ten morbidly obese patients received 1.5 g of liquid acetaminophen (APAP) orally on three separate pharmacokinetic study days (i.e., pre-RYGBS baseline and 3 and 12 months post-RYGBS). Plasma was collected at pre-specified timepoints over 24 hours, and the samples were analyzed using liquid chromatography-mass spectrometry for APAP, APAPglucuronide (APAP-gluc), APAP-sulfate (APAP-sulf), APAP-cysteine (APAP-cys), and APAP-Nacetylcysteine (APAP-nac). RESULT: Following RYGBS, peak APAP concentrations at the 3-month and 12-month visits increased by 2.0-fold compared to baseline (p=0.0039 and p=0.0078, respectively) and the median time to peak concentration decreased from 35 to 10 minutes. In contrast, peak concentrations of APAP-gluc, APAP-sulf, APAP-cys, and APAP-nac were unchanged following RYGBS. The apparent oral clearance of APAP and the ratios of metabolite area under the curve (AUC)-to-APAP AUC for all four metabolites decreased at 3 and 12 months post-RYGBS compared to the presurgical baseline. In a simulation of expected steady-state plasma concentrations following multiple dosing of 650 mg APAP every 4 hours, post-RYGBS patients had higher steady-state peak APAP concentrations compared to healthy individuals and obese pre-RYGBS patients, though APAP exposure was unchanged compared to healthy individuals. CONCLUSION: Following RYGBS, the rate and extent of APAP absorption increased and decreased formation of APAP metabolites was observed, possibly due to downregulation of Phase II and cytochrome P450 2E1 enzymes.