Key Points: oxLDL binds platelet CD36 to stimulate tyrosine kinase– and PKC-dependent activation of NOX2 and generation of ROS. oxLDL- and hyperlipidemia-induced ROS mediate platelet desensitization to inhibitory cGMP signaling to facilitate platelet activation and thrombus formation.

As zebrafish larvae are being increasingly applied to toxicity testing, there is a need to understand the potential for xenobiotic metabolism by these early life-stage organisms. The expression of genes similar to mammalian cytochromes P450 (CYP) 2B6, CYP3A5, and UDP-glucuronosyl transferase (UGT) 1A1, as well as the zebrafish CYP1A was assessed across embryonic development. Activities toward 7-ethoxyresorufin O-deethylase (EROD assay), 7-ethoxycoumarin O-deethylase (ECOD assay), and octyloxymethylresorufin (OOMR assay) were detected at 96 h postfertilization, as was significant phenolic conjugation in the EROD assay (p < 0.001). The induction of CYP1A, the CYP gene zgc:153269, and UGT1A1 after exposure to Aroclor 1254 (100 μg/L, 24 h) was observed, with significant CYP1A induction (p < 0.01). Aroclor exposure also significantly induced EROD activity (p < 0.005), as did coexposure of α-naphthoflavone in a dose-dependent manner (p < 0.05; 5 and 10 μM exposures). Inhibition of CYP activity by SKF525A (5 μM) could not be demonstrated because of significant CYP induction as evidenced by OOMR activity (p < 0.05). This study demonstrates that zebrafish larvae express genes similar to mammalian CYP and UGT isoforms throughout early development and have activities toward model CYP substrates. The modulation of these genes and activities by CYP inducers is also reported. The continued use of these model organisms in toxicity testing is supported by this study.

Organic solvents, such as dimethylsulfoxide (DMSO) and methanol are widely used as vehicles to solubilise lipophilic test compounds in toxicity testing. However, the effects of such solvents upon innate detoxification processes in aquatic organisms are poorly understood. This study assessed the effect of solvent exposure upon cytochrome P450 (CYP)-mediated xenobiotic metabolism in Daphnia magna and zebrafish larvae (4d post fertilisation). Adult D. magna were demonstrated to have a low, but detectable, metabolism of ethoxyresorufin in vivo and this activity was not modulated by pre-exposure to DMSO or methanol (24 h, up to 0.1% and 0.05% v/v, respectively). In contrast, the metabolism of ethoxyresorufin in zebrafish larvae was significantly reduced by both solvents (0.1% and 0.05% v/v, respectively) after 24 h of exposure. In zebrafish, these observed decreases in activity towards ethoxyresorufin were accompanied by decreased expression of a variety of genes coding for drug metabolising enzymes (corresponding to CYP1, CYP2, CYP3 and UDP-glucuronyl transferase [UGT] family enzymes), measured by quantitative PCR. Reduction of gene expression and CYP1 enzyme activities by methanol (0.05% v/v) in zebrafish larvae was partially reversed by co-exposure with Aroclor 1254 (100 μg L(-1)). Overall this study suggests that relatively low concentrations of organic solvents can impact upon the biotransformation of certain xenobiotics in zebrafish larvae, and that this warrants consideration when assessing compounds for metabolism and toxicity in this species.

The application of zebrafish (Danio rerio) larvae to drug discovery assays and toxicity testing, and the occurrence of pharmaceuticals in the environment, has resulted in a need to understand the e...

Raised postprandial triglycerides (TAG) and related oxidative stresses are strongly associated with increased cardiovascular disease risk. Acute exercise and strawberry ingestion independently ameliorate postprandial lipid excursions and oxidative stress. However, the combined effects of these lifestyle interventions are unknown. We investigated whether acute exercise and strawberry consumption improved postprandial responses to an oral fat tolerance test (OFTT) in overweight/obese males. Overweight/obese adult males underwent four separate OFTT (73 g fat, 33 g carbohydrate) with blood sampled at baseline and hourly for 4 h after OFTT. Two OFTT contained 25 g freeze-dried strawberries and two contained strawberry flavoring (placebo). Participants performed 40 min of submaximal high-intensity interval cycling exercise 16 h before one strawberry and one placebo OFTT and rested before the remaining two OFTT. Serum TAG was analyzed, and TAG area under the curve (AUC) and incremental AUC (iAUC) were calculated. Oxidative stress markers were measured at baseline and 4 h. Differences between conditions (strawberry/placebo and exercise/rest) were assessed using repeated-measures ANOVA. Ten males (age = 31.5, interquartile range = 17.8 yr, body mass index = 29.9 ± 1.8 kg·m−2) completed the study. TAG AUC was 1.5 mmol per 4 h−1·L−1 lower for the exercise conditions compared with the rest conditions (95% confidence interval [CI] = −2.3 to −0.8 mmol per 4 h−1·L−1, P = 0.001). TAG AUC was not different between strawberry and placebo conditions (95% CI = −1.3 to 0.6 mmol per 4 h−1·L−1, P = 0.475). TAG iAUC was 0.5 mmol per 4 h−1·L−1 greater for the strawberry compared with the placebo conditions (95% CI = 0.1 to 1.0 mmol per 4 h−1·L−1, P = 0.021). There were no changes in markers of lipid related oxidative stress (P > 0.05). Acute submaximal high-intensity interval cycling exercise appears effective in reducing postprandial lipemia in overweight/obese adult males. However, strawberry ingestion did not improve postprandial TAG.