Uremic Toxins and Protein-Bound Therapeutics in AKI and CKD: Up-to-Date Evidence

Uremic toxins are defined as harmful metabolites that accumulate in the human body of patients whose renal function declines, especially chronic kidney disease (CKD) patients. Growing evidence demonstrates the deteriorating effect of uremic toxins on CKD progression and CKD-related complications, and removing uremic toxins in CKD has become the conventional treatment in the clinic. However, studies rarely pay attention to uremic toxin clearance in the early stage of acute kidney injury (AKI) to prevent progression to CKD despite increasing reports demonstrating that uremic toxins are correlated with the severity of injury or mortality. This review highlights the current evidence of uremic toxin accumulation in AKI and the therapeutic value to prevent CKD progression specific to protein-bound uremic toxins (PBUTs).

Effects of Atmospheric CO2 and Temperature on Wheat and Corn Susceptibility to Fusarium graminearum and Deoxynivalenol Contamination

This work details the impact of atmospheric CO2 and temperature conditions on two strains of Fusarium graminearum, their disease damage, pathogen growth, mycotoxin accumulation, and production per unit fungal biomass in wheat and corn. An elevated atmospheric CO2 concentration, 1000 ppm CO2, significantly increased the accumulation of deoxynivalenol in infected plants. Furthermore, growth in cool growing conditions, 20 °C/18 °C, day and night, respectively, resulted in the highest amounts of pathogen biomass and toxin accumulation in both inoculated wheat and corn. Warm temperatures, 25 °C/23 °C, day and night, respectively, suppressed pathogen growth and toxin accumulation, with reductions as great as 99% in corn. In wheat, despite reduced pathogen biomass and toxin accumulation at warm temperatures, the fungal pathogen was more aggressive with greater disease damage and toxin production per unit biomass. Disease outcomes were also pathogen strain specific, with complex interactions between host, strain, and growth conditions. However, we found that atmospheric CO2 and temperature had essentially no significant interactions, except for greatly increased deoxynivalenol accumulation in corn at cool temperatures and elevated CO2. Plants were most susceptible to disease damage at warm and cold temperatures for wheat and corn, respectively. This work helps elucidate the complex interaction between the abiotic stresses and biotic susceptibility of wheat and corn to Fusarium graminearum infection to better understand the potential impact global climate change poses to future food security.

High Levels of Tetrodotoxin in the Flesh, Usually an Edible Part of the Pufferfish Takifugu flavipterus, Caused by Migration from the Skin and the Regional Characteristics of Toxin Accumulation

The consumption of a pufferfish, Takifugu flavipterus or komonfugu in Japanese, formerly known as Takifugu poecilonotus, is popular in Japan. However, T. flavipterus is frequently involved in cases of tetrodotoxin (TTX) poisoning in Japan. Although victims have usually consumed inedible parts, some cases are related to consumption of flesh. To improve the risk management of pufferfish poisoning, we studied TTX level in the flesh and skin of T. flavipterus. Ninety-seven specimens obtained from the Seto Inland Sea and landed in Fukuoka Prefecture were analyzed by liquid chromatography-tandem mass spectrometry. The flesh from six specimens was toxic (>10 MU/g = 2.2 mg/kg): one was in poor condition (not freeze–thawed); three were freeze–thawed before sample preparation; and two freshly prepared and in good condition (not freeze–thawed). The fillets were divided into outer and inner portions; the TTX levels in the outer portions were notably higher. The skin of the six specimens was moderately to extremely toxic: 165 MU/g (36.3 mg/kg) in the fresh specimen not in good condition, 600–950 MU/g (132–200 mg/kg) in freeze–thawed specimens, and 4500 and 6000 MU/g (990 and 1320 mg/kg) in the two fresh specimens. We concluded that TTX in the flesh migrated from the highly toxic skin. In addition, TTX levels in the skin appeared to be regionally specific. We recommend that toxic portions of T. flavipterus are removed as soon as possible after individuals are caught, and that fish from known highly toxic areas are not consumed.

Toxin breakdown does not preclude the potential for defensive toxin use in a fruit fly

Animals that ingest toxins can themselves become toxic or unpalatable to predators and parasites. However, most animals rapidly eliminate toxins to survive toxin ingestion. It is therefore unclear how species transition from susceptibility and toxin elimination to tolerance and accumulation as chemical defense emerges. Studies of chemical defense have generally focused on species that display active toxin sequestration and target-site insensitivity mutations that permit survival without necessitating toxin metabolism. Here we investigate whether animals that presumably rely on toxin elimination for survival can also utilize ingested toxins for defense. We use the A4 and A3 Drosophila melanogaster fly strains from the Drosophila Synthetic Population Resource (DSPR), which respectively possess elevated and reduced metabolic toxin resistance. We find that ingesting nicotine increased the survival of A4 but not of A3 flies against Leptopilina heterotoma wasp parasitism. Further, we find that despite possessing enhanced toxin clearance mechanisms, A4 flies accrued more nicotine than A3 individuals. Our results suggest that enhanced metabolic detoxification can allow for greater toxin intake by offsetting the cost of toxin ingestion. Passive toxin accumulation that accompanies increased toxin intake may underlie the early origins of chemical defense.

Expansion of C1Q Genes in Zhikong Scallop and Their Expression Profiling After Exposure to the Toxic Dinoflagellates

C1Q (Complement 1Q) is an important recognition molecule in the immunological complement system, which could also be putatively involved in the stress responses induced by endotoxins or exotoxins, potentially through detoxification processes. Marine bivalves are well adapted to highly complex aquatic environments with various stressors. As filter feeders, they have to cope with highly potent microalgae-derived neurotoxins, such as paralytic shellfish toxin (PSTs). Zhikong scallops, Chlamys farreri, are commercially important bivalve with the remarkable ability to accumulate PSTs. Exploring the C1Qs related to PST accumulation in C. farreri could benefit our understanding of the adaptations of bivalve species. In the present study, we systematically analyzed C1Q genes in C. farreri. In total, 97 CfC1Q genes mainly from the expanded C1Q-B subfamily were identified, from which the C1QL, C1QTNF, and C1QDC1 members in C. farreri were revealed to be under positive selection. Spatiotemporal expression analysis revealed that most CfC1QLs and CfC1QDC1s were highly expressed during the post-umbo stage and in hepatopancreas, while most CfC1QTNF members were highly expressed after the creeping larva stage and in mantle. The hepatopancreas and kidney in C. farreri are two toxin-rich organs with the highest concentrations of PSTs, acting as major “centers” for toxin accumulation and transformation, respectively. Therefore, after feeding the scallops with PST-producing dinoflagellates Alexandrium minutum and Alexandrium catenella, we determined the expression patterns of CfC1Qs in these two organs. In kidney, more than 85% of CfC1QLs and CfC1QDC1s showed drastic up-regulation with both diets. However, among these members with significant induction, a different response manner was detected after feeding with A. minutum and A. catenella, respectively as acute and chronic response patterns. In comparison, far fewer CfC1Qs showing significant up-regulation in hepatopancreas with both toxic diets and only mild regulation pattern could be found. This organ-, toxin-, and time-dependent genetic regulation of CfC1Qs may contribute to the virulence difference on account of the tissue-specific or dinoflagellate-specific different toxin analogs composition, implying the possible involvement of CfC1Qs in PST transport and homeostasis. Our findings imply the functional diversity of scallop C1Q genes in coping with PST accumulation, which might be developed as potential molecular indicators for monitoring toxin accumulation in edible mollusks or provide insight into the lineage-specific adaptation of scallops for dealing with microalgal toxin challenges.

Lobster Supply Chains Are Not at Risk from Paralytic Shellfish Toxin Accumulation during Wet Storage

Lobster species can accumulate paralytic shellfish toxins (PST) in their hepatopancreas following the consumption of toxic prey. The Southern Rock Lobster (SRL), Jasus edwardsii, industry in Tasmania, Australia, and New Zealand, collectively valued at AUD 365 M, actively manages PST risk based on toxin monitoring of lobsters in coastal waters. The SRL supply chain predominantly provides live lobsters, which includes wet holding in fishing vessels, sea-cages, or processing facilities for periods of up to several months. Survival, quality, and safety of this largely exported high-value product is a major consideration for the industry. In a controlled experiment, SRL were exposed to highly toxic cultures of Alexandrium catenella at field relevant concentrations (2 × 105 cells L−1) in an experimental aquaculture facility over a period of 21 days. While significant PST accumulation in the lobster hepatopancreas has been reported in parallel experiments feeding lobsters with toxic mussels, no PST toxin accumulated in this experiment from exposure to toxic algal cells, and no negative impact on lobster health was observed as assessed via a wide range of behavioural, immunological, and physiological measures. We conclude that there is no risk of PST accumulation, nor risk to survival or quality at the point of consumption through exposure to toxic algal cells.

Cinnamaldehyde Could Reduce the Accumulation of Diarrhetic Shellfish Toxins in the Digestive Gland of the Mussel Perna viridis under Laboratory Conditions

Diarrhetic shellfish toxins (DSTs), some of the most important phycotoxins, are distributed almost all over the world, posing a great threat to human health through the food chain. Therefore, it is of great significance to find effective methods to reduce toxin accumulation in shellfish. In this paper, we observed the effects of four phytochemicals including cinnamaldehyde (CA), quercetin, oridonin and allicin on the accumulation of DSTs in the digestive gland of Perna viridis after exposure to the DSTs-producing Prorocentrum lima. We found that, among the four phytochemicals, CA could effectively decrease the accumulation of DSTs (okadaic acid-eq) in the digestive gland of P. viridis. Further evidence demonstrated that CA could reduce the histological alterations of the digestive gland of a mussel caused by DSTs. RT-qPCR showed that CA could suppress the CYP3A4 induction by DSTs, suggesting that the DSTs’ decrease induced by CA might be related to the inhibition of CYP3A4 transcription induction. However, further studies on the underlying mechanism, optimal treatment time, ecological safety and cost should be addressed before cinnamaldehyde is used to decrease the accumulation of DSTs in field.

A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy—quasi-paired cohort—and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD.

The Effects of Selenium on Wheat Fusarium Head Blight and DON Accumulation Were Selenium Compound-Dependent

Fusarium head blight (FHB) caused by Fusarium graminearum not only results in severe yield losses, but also contaminates wheat grains with deoxynivalenol (DON) toxins. Prevention and control of FHB and DON contamination rely mainly on resistant varieties and fungicides. Selenium (Se) is an essential element for humans and animals, and also a beneficial element for plants. In this work, four Se compounds, i.e., sodium selenite (Na2SeO3), sodium selenate (Na2SeO4), selenomethionine (SeMet) and selenocysteine (SeCys2), were supplemented in a trichothecene biosynthesis induction (TBI) solid medium at different dosages in in vitro experiments. The four Se compounds at the dosage of 20 mg∙L−1 were sprayed onto wheat spikes immediately after inoculation at anthesis. All four of the Se compounds significantly inhibited the mycelial growth and DON production in the in vitro experiment; however, in planta, their effects on FHB severity and toxin accumulation in grains were compound-dependent. SeMet consistently negatively regulated fungal growth and DON accumulation both in vitro and in planta, which could be a novel and proconsumer strategy for reducing the detriment of wheat FHB disease and DON accumulation.