Hepatotoxicity Comparison of Crude and Licorice-Processed Euodiae Fructus in Rats With Stomach Excess-Cold Syndrome

In recent years, drug-induced liver injury (DILI) has become an important issue of public health. Euodiae Fructus (EF) is a commonly used herb with mild toxicity in clinic, and large doses of EF can cause significant liver damage. Licorice processing might reduce the hepatotoxicity of CEF (crude EF), but up to now, studies on the hepatotoxicity of EF have been hardly reported, let alone its material basis and mechanism of detoxification by licorice processing. This work firstly established a stomach excess-cold syndrome animal model induced by intragastric administration of cold Zhimu (Anemarrhena asphodeloides Bge). Secondly, multiple approaches and indexes were used to evaluate the hepatotoxicity of the drugs in the rats including general behavior, biochemical analysis, protein expressions, and histopathological examination. Thirdly, the hepatotoxicity of three doses of three CEF and LPEF (licorice-processed EF) extracts was systematically investigated, and the hepatotoxicity differences were analyzed and compared comprehensively among the three extracts, three doses, and CEF and LPEF. Finally, the connotation of detoxification of EF by licorice processing was preliminarily discussed according to the changes in toxic components after processing, toxicological characteristics, and TCM (traditional Chinese medicine) theory. All extracts of EF were found to have dose-dependent hepatotoxicity, and the toxicity was in the descending order of water extract, ethanol extract, and volatile oil. The hepatotoxic mechanism of EF may be related to peroxidation damage, inflammatory factor, and mitochondrial injury. The CEF hepatotoxicity can be significantly reduced by licorice processing. EF should be safe for short-term use at pharmacopeial dose under the guidance of the TCM theory. The detoxification mechanism is probably related to the reduction of toxic components and antagonistic action of licorice.

Anthrahydroquinone-2-6-disulfonate is a novel, powerful antidote for paraquat poisoning

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2’s expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.

Pharmaceutical Compounds in Aquatic Environments—Occurrence, Fate and Bioremediation Prospective

Various contaminants of emerging concern (CECs) have been detected in different ecosystems, posing a threat to living organisms and the environment. Pharmaceuticals are among the many CECs that enter the environment through different pathways, with wastewater treatment plants being the main input of these pollutants. Several technologies for the removal of these pollutants have been developed through the years, but there is still a lack of sustainable technologies suitable for being applied in natural environments. In this regard, solutions based on natural biological processes are attractive for the recovery of contaminated environments. Bioremediation is one of these natural-based solutions and takes advantage of the capacity of microorganisms to degrade different organic pollutants. Degradation of pollutants by native microorganisms is already known to be an important detoxification mechanism that is involved in natural attenuation processes that occur in the environment. Thus, bioremediation technologies based on the selection of natural degrading bacteria seem to be a promising clean-up technology suitable for application in natural environments. In this review, an overview of the occurrence and fate of pharmaceuticals is carried out, in which bioremediation tools are explored for the removal of these pollutants from impacted environments.

UPLC-MS/MS-Based Rat Serum Metabolomics Reveals the Detoxification Mechanism of Psoraleae Fructus during Salt Processing

Psoraleae Fructus (PF) is a botanical medicine widely used in Asian countries, of which salt products have higher safety and efficacy. However, the biological mechanism of the detoxification of salt-processing Psoraleae Fructus (SPF) has not yet been revealed. In this study, UPLC-MS/MS technology was used to explore the metabolic differences between SPF and PF in normal rats and reveal the mechanism of salt processing. The histopathological results of rat liver and kidney showed that the degree of liver and kidney injure in the SPF group was less than that in the PF group. The results of metabolomics showed that the detoxification mechanism of PF by salt processing might be related to glycerophospholipid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, arginine and proline metabolism, phenylalanine metabolism, and linoleic acid metabolism. PF-induced inflammation could be reduced by regulating the expression of metabolites to achieve the purpose of salt processing and detoxification. It included reducing the production of metabolites such as 1-acyl-sn-glycero-3-phosphocholine, sn-glycero-3-phosphocholine, tyrosine, arginine, linoleic acid, arachidonic acid, and phenylacetylglycine/hippuric acid ratio and upregulating the expression of metabolites such as creatine.

Evolution and enrichment of CYP5035 in Polyporales: functionality of an understudied P450 family

Bioprospecting for innovative basidiomycete cytochrome P450 enzymes (P450s) is highly desirable due to the fungi’s enormous enzymatic repertoire and outstanding ability to degrade lignin and detoxify various xenobiotics. While fungal metagenomics is progressing rapidly, the biocatalytic potential of the majority of these annotated P450 sequences usually remains concealed, although functional profiling identified several P450 families with versatile substrate scopes towards various natural products. Functional knowledge about the CYP5035 family, for example, is largely insufficient. In this study, the families of the putative P450 sequences of the four white-rot fungi Polyporus arcularius, Polyporus brumalis, Polyporus squamosus and Lentinus tigrinus were assigned, and the CYPomes revealed an unusual enrichment of CYP5035, CYP5136 and CYP5150. By computational analysis of the phylogeny of the former two P450 families, the evolution of their enrichment could be traced back to the Ganoderma macrofungus, indicating their evolutionary benefit. In order to address the knowledge gap on CYP5035 functionality, a representative subgroup of this P450 family of P. arcularius was expressed and screened against a test set of substrates. Thereby, the multifunctional enzyme CYP5035S7 converting several plant natural product classes was discovered. Aligning CYP5035S7 to 102,000 putative P450 sequences of 36 fungal species from Joint Genome Institute-provided genomes located hundreds of further CYP5035 family members, which subfamilies were classified if possible. Exemplified by these specific enzyme analyses, this study gives valuable hints for future bioprospecting of such xenobiotic-detoxifying P450s and for the identification of their biocatalytic potential. Graphical abstract Key points • The P450 families CYP5035 and CYP5136 are unusually enriched in P. arcularius. • Functional screening shows CYP5035 assisting in the fungal detoxification mechanism. • Some Polyporales encompass an unusually large repertoire of detoxification P450s.

Eco-friendly intracellular biosynthesis of CdS quantum dots using Pseudomonas aeruginosa: Evaluation of antimicrobial effects and DNA cleavage activities

Background: Intracellular biosynthesis of quantum dots (QDs) based on microorganisms offers a green alternative and eco-friendly for the production of nanocrystals with superior properties. This study focused on the production of intracellular CdS QDs by stimulating the detoxification metabolism of Pseudomonas aeruginosa. Methods: For this aim, Pseudomonas aeruginosa ATCC 27853 strain was incubated in a solution of 1mM cadmium sulphate (CdSO4) to manipulate the detoxification mechanism. The intracellularly formed Cd-based material was extracted, and its characterization was carried out by transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray (EDX) and dynamic light scattering (DLS) analyses and absorption-emission spectra. Results: The obtained material showed absorption peaks at 385 nm and a luminescence peak at 411 nm, and the particle sizes were measured in the range 4.63-17.54 nm. It was determined that the material was sphere-shaped, with a cubic crystalline structure, including Cd and S elements. The agar disk diffusion method investigated the antibacterial and antifungal activities of CdS QDs against eleven bacterial (four Gram-positive and seven Gram-negative) and one fungal strain. It was revealed that the obtained material has antibacterial effects on both Gram-positive and Gram-negative bacteria. However, cleavage activity of CdS QDs on pBR322 DNA was not detected. Conclusion: As a result, it has been proposed that the stimulation of the detoxification mechanism can be an easy and effective way of producing green and cheap luminescent QDs or nanomaterial.