RESUMEN
To date, the presence of pharmaceuticals has been extensively documented across a wide range of aquatic systems and biota. Further, substantial progress has been made in transitioning from laboratory assessments of pharmaceutical fate and effects in fish to in situ assessments of exposure and effects; however, certain research areas remain understudied. Among these is investigation of differential accumulation across multiple internal tissues in wild marine fish beyond the species commonly sampled in laboratory and freshwater field settings. This study examined the presence of pharmaceuticals across four tissues (plasma, muscle, brain, and liver) in a wild marine fish, bonefish (Albula vulpes), throughout coastal South Florida, USA. Differential accumulation across tissues was assessed for the number and concentration, identity, and composition of accumulated pharmaceuticals by sampling 25 bonefish and analyzing them for 91 pharmaceuticals. The concentration of pharmaceuticals was highest in plasma > liver > brain > muscle, while the number of pharmaceuticals was highest in liver > brain > plasma > muscle. The identity of detected pharmaceuticals was tissue specific, and there was an inverse relationship between the number of detections for each pharmaceutical and its log Kow. The composition of pharmaceuticals was tissue specific for both pharmaceutical presence/absence and concentration. Across all tissues, the greatest similarity was between brain and liver, which were more similar to plasma than to muscle, and muscle was the most distinct tissue. For tissue compositional variability, muscle was the most diverse in accumulated pharmaceuticals, while plasma, brain, and liver were similarly variable. With the highest concentrations in plasma and highest number in liver, and documented variability in accumulated pharmaceuticals across tissues, our results highlight the importance of tissue selection when surveying exposure in wild fish, suggesting that multi-tissue analysis would allow for a more comprehensive assessment of exposure diversity and risk of adverse effects.
Asunto(s)
Peces , Hígado , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/análisis , Distribución Tisular , Preparaciones Farmacéuticas/análisis , Preparaciones Farmacéuticas/metabolismo , Hígado/química , Hígado/metabolismo , Peces/metabolismo , Músculos/química , Músculos/metabolismo , Florida , Monitoreo del Ambiente , Encéfalo/metabolismoRESUMEN
Pharmaceutical uptake involves processes that vary across aquatic systems and biota. However, single studies examining multiple environmental compartments, microhabitats, biota, and exposure pathways in mesoconsumer fish are sparse. We investigated the pharmaceutical burden in bonefish (Albula vulpes), pathways of exposure, and estimated exposure to a human daily dose. To evaluate exposure pathways, the number and composition of pharmaceuticals across compartments and the bioconcentration in prey and bonefish were assessed. To evaluate bioaccumulation, we proposed the use of a field-derived bioaccumulation factor (fBAF), due to variability inherent to natural systems. Exposure to a human daily dose was based on bonefish daily energetic requirements and consumption rates using pharmaceutical concentrations in prey. Pharmaceutical number and concentration were highest in prey, followed by bonefish, water and sediment. Fifteen pharmaceuticals were detected in common among bonefish, prey, and water; all of which bioconcentrated in prey and bonefish, and four bioaccumulated in bonefish. The composition of detected pharmaceuticals was compartment specific, and prey were most similar to bonefish. Bonefish were exposed to a maximum of 1.2 % of a human daily dose via prey consumption. Results highlight the need for multicompartment assessments of exposure and consideration of prey along with water as a pathway of exposure.
Asunto(s)
Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/farmacocinética , Preparaciones Farmacéuticas/metabolismo , Preparaciones Farmacéuticas/análisis , Peces/metabolismo , Bioacumulación , Cadena Alimentaria , Monitoreo del Ambiente , HumanosRESUMEN
Most research on pharmaceutical presence in the environment to date has focused on smaller scale assessments of freshwater and riverine systems, relying mainly on assays of water samples, while studies in marine ecosystems and of exposed biota are sparse. This study investigated the pharmaceutical burden in bonefish (Albula vulpes), an important recreational and artisanal fishery, to quantify pharmaceutical exposure throughout the Caribbean Basin. We sampled 74 bonefish from five regions, and analyzed them for 102 pharmaceuticals. We assessed the influence of sampling region on the number of pharmaceuticals, pharmaceutical assemblage, and risk of pharmacological effects. To evaluate the risk of pharmacological effects at the scale of the individual, we proposed a metric based on the human therapeutic plasma concentration (HTPC), comparing measured concentrations to a threshold of 1/3 the HTPC for each pharmaceutical. Every bonefish had at least one pharmaceutical, with an average of 4.9 and a maximum of 16 pharmaceuticals in one individual. At least one pharmaceutical was detected in exceedance of the 1/3 HTPC threshold in 39% of bonefish, with an average of 0.6 and a maximum of 11 pharmaceuticals exceeding in a Key West individual. The number of pharmaceuticals (49 detected in total) differed across regions, but the risk of pharmacological effects did not (23 pharmaceuticals exceeded the 1/3 HTPC threshold). The most common pharmaceuticals were venlafaxine (43 bonefish), atenolol (36), naloxone (27), codeine (27), and trimethoprim (24). Findings suggest that pharmaceutical detections and concentration may be independent, emphasizing the need to monitor risk to biota regardless of exposure diversity, and to focus on risk quantified at the individual level. This study supports the widespread presence of pharmaceuticals in marine systems and shows the utility of applying the HTPC to assess the potential for pharmacological effects, and thus quantify impact of exposure at large spatial scales.
Asunto(s)
Ecosistema , Contaminantes Químicos del Agua , Humanos , Animales , Peces , Región del Caribe , Biota , Preparaciones Farmacéuticas , Contaminantes Químicos del Agua/toxicidad , Monitoreo del AmbienteRESUMEN
Intrathecal (IT) gene transfer using adeno-associated virus (AAV) may be clinically promising as a treatment for chronic pain if it can produce sufficiently high levels of a transgene product in the cerebrospinal fluid (CSF). Although this strategy was developed in rodents, no studies investigating CSF levels of an analgesic or antiallodynic protein delivered by IT AAV have been performed in large animals. Interleukin-10 (IL-10) is an antiallodynic cytokine for which target therapeutic levels have been established in rats. The present study tested IT AAV8 encoding either human IL-10 (hIL-10) or enhanced green fluorescent protein (EGFP) in a dog model of IT drug delivery. AAV8/hIL-10 at a dose of 3.5 × 10(12) genome copies induced high hIL-10 levels in the CSF, exceeding the target concentration previously found to be antiallodynic in rodents by >1000-fold. AAV8/EGFP targeted the primary sensory and motor neurons and the meninges. hIL-10, a xenogeneic protein in dogs, induced anti-hIL-10 antibodies detectable in the CSF and serum of dogs. The high hIL-10 levels demonstrate the efficacy of AAV for delivery of secreted transgenes into the IT space of large animals, suggesting a strong case for further development toward clinical testing.