Interactions of Environmental Chemicals and Natural Products With ABC and SLC Transporters in the Digestive System of Aquatic Organisms

An organism’s diet is a major route of exposure to both beneficial nutrients and toxic environmental chemicals and natural products. The uptake of dietary xenobiotics in the intestine is prevented by transporters of the Solute Carrier (SLC) and ATP Binding Cassette (ABC) family. Several environmental chemicals and natural toxins have been identified to induce expression of these defense transporters in fish and aquatic invertebrates, indicating that they are substrates and can be eliminated. However, certain environmental chemicals, termed Transporter-Interfering Chemicals or TICs, have recently been shown to bind to and inhibit fish and mammalian P-glycoprotein (ABCB1), thereby sensitizing cells to toxic chemical accumulation. If and to what extent other xenobiotic defense or nutrient uptake transporters can also be inhibited by dietary TICs is still unknown. To date, most chemical-transporter interaction studies in aquatic organisms have focused on ABC-type transporters, while molecular interactions of xenobiotics with SLC-type transporters are poorly understood. In this perspective, we summarize current advances in the identification, localization, and functional analysis of protective MXR transporters and nutrient uptake systems in the digestive system of fish and aquatic invertebrates. We collate the existing literature data on chemically induced transporter gene expression and summarize the molecular interactions of xenobiotics with these transport systems. Our review emphasizes the need for standardized assays in a broader panel of commercially important fish and seafood species to better evaluate the effects of TIC and other xenobiotic interactions with physiological substrates and MXR transporters across the aquatic ecosystem and predict possible transfer to humans through consumption.

Contamination of hay and haylage with enteric bacteria and selected antibiotic resistance genes following fertilization with dairy manure or biosolids.

The present study evaluated if enteric bacteria or antibiotic resistance genes carried in fecal amendments contaminate the hay at harvest, representing a potential route of exposure to ruminants that consume the hay. In field experiments, dairy manure was applied to a hay field for three successive growing seasons, and biosolids applied to a hay field for one growing season. Various enteric bacteria in the amendments were enumerated by viable plate count, and selected gene targets were quantified by qPCR. Key findings include the following: At harvest, hay receiving dairy manure or biosolids did not carry more viable enteric bacteria than did hay from unamended control plots. Fermentation of hay did not result in a detectable increase in viable enteric bacteria. The application of dairy manure or biosolids did result in a few gene targets being more abundant on hay at the first harvest. Fermentation of hay did result in an increase in the abundance of gene targets, but this occurred both with hay from amended and control plots. Overall, application of fecal amendments will result in an increase in the abundance of some gene targets associated with antibiotic resistance on first cut hay.

Prevalence and Characteristics of Cannabis-induced Toxicoses in Pets: Results from a Survey of Veterinarians in North America

Cannabis legalization in North America has coincided with an increase in reports of cannabis-induced toxicosis in pets, but the magnitude of this problem, as well as outcomes of these incidents remain unknown. Therefore, we examined the frequency, diagnostic criteria, clinical signs, and prognoses of cannabis toxicoses in pets in North America. We conducted an online survey between January, 2021 and April, 2021 targeting veterinarians practicing in Canada and the United States (US). Out of the 251 study participants, 191 practiced in Canada. Cannabis toxicosis was most commonly reported in dogs (n=226 veterinarians), and the number of toxicosis cases increased significantly in Canada (p<0.0001) and the US (p=0.002) after October, 2018. Frequently reported clinical signs of cannabis toxicosis included: urinary incontinence (n=195), disorientation (n=182), ataxia (n=178), lethargy (n=150), hyperesthesia (n=134), and bradycardia (n=112). Edibles were most commonly suspected to be the cause of toxicosis (n=116). The most common route of exposure was ingestion (n=135), while the most cited reason was ingestion while unattended (n=135). Cannabis toxicosis was mostly diagnosed using supportive clinical signs (n=229), the most common treatment was outpatient monitoring (n=182), and pets were most often treated as out-patients (n=103). The legalization of cannabis use in Canada and the US is likely an important factor associated with the increased cannabis toxicosis cases in pets; however, the legal status may also increase reporting. The medicinal use of cannabis by pet-owners for pets may also contribute to a portion of the reported toxicoses. Most pets that experienced cannabis toxicosis recovered completely, suggesting that most cannabis toxicoses do not result in long-term ill effects. Even though some deaths (n=16) were reported in association with cannabis toxicosis, the presence of confounders such as toxins, and underlying conditions cannot be ruled out, emphasizing the need for rigorous controlled laboratory studies to investigate this important issue.

Impact of COVID-19 lockdown on the incidence and patterns of toxic exposures and poisoning in Jordan: a retrospective descriptive study

ObjectivesTo describe the effect of the COVID-19 lockdown in Jordan (21 March 2020–21 May 2020) on the incidence and patterns of toxic exposures and poisoning as compared with the same period from the previous year (21 March 2019–21 May 2019).DesignA retrospective descriptive study.MethodsCall data sourced from Pharmacy One Poison Center from the lockdown period (21 March 2020–21 May 2020) and the same period during 2019 (21 March 2019–21 May 2019) were revised. In addition, a database was established and analysed.ResultsWe noticed that not only did calls increased, but there was also a noticeable change in call patterns. Calls increased by 91% (544 vs 285 calls) during the lockdown period. Drugs were the most common among types of exposure, and the most prevalent route of exposure was ingestion. There was a notable increase in ocular exposure by 550% (13 vs 2 cases). The majority of exposures were at home and there were no occupational exposures. We found an increase in household cleaner exposure among males and an increase in alcohol exposure in females. Children aged below 5 years are the most affected. Even though there is an increase in the total number of cases, severe cases decreased.ConclusionThe lockdown effect on rates of toxic exposures was prominent, whether through the increase in calls or the change in patterns. As people spent more time at home, their exposure to toxic agents increased. Furthermore, cleaning recommendations led to the misuse of cleaning and disinfectant products, increasing exposures related to abating the COVID-19 infection.

A nucleic acid-based orthopoxvirus vaccine targeting the vaccinia virus L1, A27, B5 and A33 proteins protects rabbits against lethal rabbitpox virus aerosol challenge

In the age of COVID, nucleic acid vaccines have garnered much attention, at least in part, because of the simplicity of construction, production, and flexibility to adjust and adapt to an evolving outbreak. Orthopoxviruses remain a threat on multiple fronts, especially as emerging zoonosis. In response, we developed a DNA vaccine, termed 4pox, that protected nonhuman primates against monkeypox virus (MPXV) induced severe disease. Here, we examined the protective efficacy of the 4pox DNA vaccine delivered by intramuscular (i.m.) electroporation (EP) in rabbits challenged with aerosolized rabbitpox virus (RPXV), a model that recapitulates the respiratory route of exposure and low dose associated with natural smallpox exposure in humans. We found that 4pox vaccinated rabbits developed immunogen-specific antibodies, including neutralizing antibodies and did not develop any clinical disease, indicating protection against aerosolized RPXV. In contrast, unvaccinated animals developed significant signs of disease, including lesions, and were euthanized. These findings demonstrate that an unformulated, non-adjuvanted DNA vaccine delivered (i.m.) can protect against an aerosol exposure. Importance The eradication of smallpox and subsequent cessation of vaccination has left a majority of the population susceptible to variola virus or other emerging poxvirus. This is exemplified by human monkeypox, as evidenced by the increase in reported endemic and imported cases over the past decades. Therefore, a malleable vaccine technology that can be mass produced, and doesn’t require complex conditions for distribution and storage is sought. Herein, we show that a DNA vaccine, in the absence of a specialized formulation or adjuvant, can protect against a lethal aerosol insult of rabbitpox virus.

Temporal Baseline of Essesntial and Non-essential Elements Recorded in Baleen of Western Arctic Bowhead Whale (Balaena mysticetus)

This study established the first baseline of changing elemental concentrations in bowhead whale baleen over time (1958–1999). From previously published stable isotope data, year, season (summer or winter), and location (Beaufort or Bering/Chukchi seas) were attributed to each sample. Thirteen elements (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, V, Zn) in baleen from nine subsistence-harvested bowhead whales (n = 138) were detected. Al, Cu, and Fe were the highest concentrations while Cd and V were among the lowest. Our data supports absorption as the main route of exposure to environmental elements rather than biomagnification due to bowhead whales’ low trophic position. A linear mixed-effects model confirmed most elements’ concentrations increased with time, while location and sex were insignificant explanatory factors. These temporal fluctuations were most likely a product of environmental changes due to a warming climate and human activities.

Prognostic factors of acetaminophen exposure in the United States: An analysis of 39,000 patients

Acetaminophen is a frequently used over-the-counter or prescribed medication in the United States. Exposure to acetaminophen can lead to acute liver cytolysis, acute liver failure, acute kidney injury, encephalopathy, and coagulopathy. This retrospective cohort study (1/1/2012 to 12/31/2017) investigated the clinical outcomes of intentional and unintentional acetaminophen exposure using the National Poison Data System data. The frequency of outcomes, chronicity, gender, route of exposure, the reasons for exposure, and treatments as described. Binary logistic regression was used to estimate the prognostic factors and odds ratios (OR) with 95% confidence intervals (CI) for outcomes. This study included 39,022 patients with acetaminophen exposure. Our study demonstrated that the likelihood of developing severe outcomes increased by aging (OR = 1.12, 95% CI: 1.08–1.015) and was lower in females (OR = 0.88, 95% CI: 0.78–0.99). Drowsiness/lethargy (OR = 1.48, 95% CI: 1.22–1.82), agitation (OR = 1.66, 95% CI: 1.11–2.50), coma (OR = 23.95, 95% CI: 17.05–33.64), bradycardia (OR = 2.29, 95% CI: 1.22–4.32), rhabdomyolysis (OR = 8.84, 95% CI: 3.71–21.03), hypothermia (OR = 4.1, 95% CI: 1.77–9.51), and hyperthermia 2.10 (OR = 2.10, 95% CI: 1.04–4.22) were likely associated with major outcomes or death. Treatments included intravenous N-acetylcysteine (61%), oral N-acetylcysteine (10%), vasopressor (1%), hemodialysis (0.7%), fomepizole (0.1%), hemoperfusion (0.03%), and liver transplant (0.1%). In conclusion, it is important to consider clinical presentations of patients with acetaminophen toxicity that result in major outcomes and mortality to treat them effectively.

Microplastic Abundance in Blood Cockles and Shrimps from Fishery Market, Songkhla Province, Southern Thailand

Microplastics have been one of the major pollutants in the marine environment throughout the recent decade. At present, microplastic contamination in marine ecosystems of Thailand region has become an increasing environmental concern because the ingestion of microplastics in marine organisms may adversely influence the safety of seafood. Cockles and shrimps widely distribute among marine organisms in Thailand since they are one of the commercial sources of seafood, which may be a route of exposure to microplastics towards human. This study documents a market survey in order to understand the extension of microplastic presence in blood cockles (Anadara granosa), fine shrimp (Metapenaeus elegans) and Indian white shrimp (Fenneropenaeus indicus) sold in the fishery market in Singhanakorn district, Songkhla province. These selected species are widely consumed and economically important, especially in the southern Thailand region. The total microplastic concentration in blood cockles is 4.71±0.06 n/g (wet weight) and 2.64±0.01 n/individual; in fine shrimp is 0.50±0.19 n/g (wet weight) and 3.70±1.12 n/individual; in Indian white shrimp is 0.69±0.48 n/g (wet weight) and 3.45±0.04n/individual. Discovered microplastics in all the species samples were mainly composed of microplastic fibres and black colour was found to be more predominant. Our results indicate that microplastic contamination is present in Thailand’s commercial seafood species. As microplastic able to be transferred to human through food web, we suggest further market-based survey studies on other seafood sources.

Surveillance of laboratory exposures to human pathogens and toxins, Canada 2020

Background: The Laboratory Incident Notification Canada surveillance system monitors laboratory incidents reported under the Human Pathogens and Toxins Act and the Human Pathogens and Toxins Regulations. The objective of this report is to describe laboratory exposures that were reported in Canada in 2020 and the individuals who were affected. Methods: Laboratory incident exposures occurring in licensed Canadian laboratories in 2020 were analyzed. The exposure incident rate was calculated and the descriptive statistics were performed. Exposure incidents were analyzed by sector, activity type, occurrence type, root cause and pathogen/toxin. Affected persons were analyzed by education, route of exposure sector, role and laboratory experience. The time between the incident and the reporting date was also analyzed. Results: Forty-two incidents involving 57 individuals were reported to Laboratory Incident Notification Canada in 2020. There were no suspected or confirmed laboratory acquired infections. The annual incident exposure rate was 4.2 incidents per 100 active licenses. Most exposure incidents occurred during microbiology activities (n=22, 52.4%) and/or were reported by the hospital sector (n=19, 45.2%). Procedural issues (n=16, 27.1%) and sharps-related incidents (n=13, 22.0%) were the most common occurrences. Most affected individuals were exposed via inhalation (n=28, 49.1%) and worked as technicians or technologists (n=36, 63.2%). Issues with standard operating procedures was the most common root cause (n=24, 27.0%), followed by human interactions (n=21, 23.6%). The median number of days between the incident and the reporting date was six days. Conclusion: The rate of laboratory incidents were lower in 2020 than 2019, although the ongoing pandemic may have contributed to this decrease because of the closure of non-essential workplaces, including laboratories, for a portion of the year. The most common occurrence type was procedural while issues with not complying to standard operating procedures and human interactions as the most cited root causes.

Enigmatic mechanism of the N-vinylpyrrolidone hepatocarcinogenicity in the rat

N-vinyl pyrrolidone (NVP) is produced up to several thousand tons per year as starting material for the production of polymers to be used in pharmaceutics, cosmetics and food technology. Upon inhalation NVP was carcinogenic in the rat, liver tumor formation is starting already at the rather low concentration of 5 ppm. Hence, differentiation whether NVP is a genotoxic carcinogen (presumed to generally have no dose threshold for the carcinogenic activity) or a non-genotoxic carcinogen (with a potentially definable threshold) is highly important. In the present study, therefore, the existing genotoxicity investigations on NVP (all showing consistently negative results) were extended and complemented with investigations on possible alternative mechanisms, which also all proved negative. All tests were performed in the same species (rat) using the same route of exposure (inhalation) and the same doses of NVP (5, 10 and 20 ppm) as had been used in the positive carcinogenicity test. Specifically, the tests included an ex vivo Comet assay (so far not available) and an ex vivo micronucleus test (in contrast to the already available micronucleus test in mice here in the same species and by the same route of application as in the bioassay which had shown the carcinogenicity), tests on oxidative stress (non-protein-bound sulfhydryls and glutathione recycling test), mechanisms mediated by hepatic receptors, the activation of which had been shown earlier to lead to carcinogenicity in some instances (Ah receptor, CAR, PXR, PPARα). No indications were obtained for any of the investigated mechanisms to be responsible for or to contribute to the observed carcinogenicity of NVP. The most important of these exclusions is genotoxicity. Thus, NVP can rightfully be regarded and treated as a non-genotoxic carcinogen and threshold approaches to the assessment of this chemical are supported. However, the mechanism underlying the carcinogenicity of NVP in rats remains unclear.