Metabonomics analysis of microalga Scenedesmus obliquus under ciprofloxacin stress.

The wide use of antibiotics in aquaculture has triggered global ecological security issue. Microalgal bioremediation is a promising strategy for antibiotics elimination due to carbon recovery, detoxification and various ecological advantages. However, a lack of understanding with respect to the corresponding regulation mechanism towards antibiotic stress may limit its practical applicability. The microalga Scenedesmus obliquus was shown to be capable of effectively eliminating ciprofloxacin (CIP), which is a common antibiotic used in aquaculture. However, the corresponding transcriptional alterations require further investigation and verification at the metabolomic level. Thus, this study uncovered the metabolomic profiles and detailed toxic and defense mechanisms towards CIP in S. obliquus using untargeted metabolomics. The enhanced oligosaccharide/polyol/lipid transport, up-regulation of carbohydrate and arachidonic acid metabolic pathways and increased energy production via EMP metabolism were observed as defense mechanisms of microalgal cells to xenobiotic CIP. The toxic metabolic responses included: (1) down-regulation of parts of mineral and organic transporters; (2) electrons competition between antibiotic and NAD during intracellular CIP degradation; and (3) suppressed expression of the hem gene in chlorophyll biosynthesis. This study describes the metabolic profile of microalgae during CIP elimination and reveals the key pathways from the perspective of metabolism, thereby providing information on the precise regulation of antibiotic bioremediation via microalgae.

Plumbagin can potently enhance the activity of xanthine oxidase: in vitro, in vivo and in silico studies.

BACKGROUND: Abnormally elevated xanthine oxidase (XO) activity has been verified to cause various pathological processes, such as gout, oxidative stress injury and metabolic syndrome. Thus, XO activators may exhibit above potential toxicological properties. Plumbagin (PLB) is an important active compound in traditional Chinese medicine (TCM), while its obvious toxic effects have been reported, including diarrhea, skin rashes and hepatic toxicity. However, the potential toxicity associated with enhancement of XO activity has not been fully illuminated so far. METHODS: The present study investigated the effect of PLB on XO activity by culturing mouse liver S9 (MLS9), human liver S9 (HLS9), XO monoenzyme system with PLB and xanthine. Then, the molecular docking and biolayer interferometry analysis were adopted to study the binding properties between PLB and XO. Finally, the in vivo acceleration effect also investigated by injected intraperitoneally PLB to KM mice for 3 days. RESULTS: PLB could obviously accelerate xanthine oxidation in the above three incubation systems. Both the Vmax values and intrinsic clearance values (CLint, Vmax/Km) of XO in the three incubation systems increased along with elevated PLB concentration. In addition, the molecular docking study and label-free biolayer interferometry assay displayed that PLB was well bound to XO. In addition, the in vivo results showed that PLB (2 and 10 mg/kg) significantly increased serum uric acid levels and enhanced serum XO activity in mice. CONCLUSION: In summary, this study outlines a potential source of toxicity for PLB due to the powerful enhancement of XO activity, which may provide the crucial reminding for the PLB-containing preparation development and clinical application.

How Can Xenosensors Act in Chemical Detoxification Metabolism?

There are some disparities between pharmacological and toxicological xenobiotic receptor (xenosensors) pathways. These variations include receptor models that indicate several toxic patterns. Such models have demanded some update from traditional medical receptor relations studied by pharmacologists. These may include the response time, the molecular level, and unclear directions of toxicological metabolism. Xenosensors activities were affected by many factors that include genetic elements, physiological status, xenobiotic complication, and species-specific variations. Thus, this review aims to highlight the most advanced features of xenosensors related to toxicant biotransformations and other patterns such as characteristics, recognition, and the relations between different xenosensors.

The discrimination of excess toxicity from baseline effect: effect of bioconcentration.

Toxic ratio TR is a valuable tool in the discrimination of excess toxicity from baseline effect. Although some authors realized that internal effect concentration or critical body residual (CBR) calculated from bioconcentration factor (BCF) should be used in the TR, the effect of BCF on the discrimination of excess toxicity from baseline effect has not been investigated. In this paper, 951 acute toxicity data to fish (LC50) and 1088 BCFs were used to investigate the relationship between TR and BCF. The results showed that some compounds identified as reactive compounds exhibit excess toxicity, but some do not. BCF is closely related to TR and can significantly affect the TR value. The real excess toxicity which is used to identify reactive chemicals from baseline should be based on the toxic ratio of internal effect concentrations, rather than on the ratio of external effect concentrations, TR. The use of LC50 alone to determine TR can result in errors in TR because toxicokinetics (as estimated by the BCF) are ignored. The foundation in the discrimination of excess toxicity from baseline effect is based on the linear relationship between log BCF and hydrophobicity expressed as log KOW. However, log BCF is not linearly related with log KOW for all the compounds. The BCFs with log KOW >7 or <0 are either overestimated or underestimated by the linear baseline BCF model. Parallel lines are observed from calculated log CBR values for baseline and less inert compounds. The log BCF values overestimated or underestimated by log KOW from the baseline BCF model can result in mis-prediction and mis-classification among baseline, less inert and reactive compounds.