Response of Aerobic Granular Sludge to the Long-Term Presence of CuO NPs in A/O/A SBRs: Nitrogen and Phosphorus Removal, Enzymatic Activity, and the Microbial Community.

The increasing use of cupric oxide nanoparticles (CuO NPs) has raised concerns about their potential environmental toxicity. Aerobic granular sludge (AGS) is a special form of microbial aggregates. In this study, the removal efficiencies of nitrogen and phosphorus, enzyme activities and microbial community of AGS under long-term exposure to CuO NPs (at concentrations of 5, 20, 50 mg/L) in aerobic/oxic/anoxic (A/O/A) sequencing batch reactors (SBRs) were investigated. The results showed the chronic toxicity caused by different concentrations of CuO NPs (5, 20, 50 mg/L) resulted in increases in the production of ROS of 110.37%, 178.64%, and 188.93% and in the release of lactate dehydrogenase (LDH) of 108.33%, 297.05%, 335.94%, respectively, compared to the control. Besides, CuO NPs decreased the activities of polyphosphate kinase (PPK) and exophosphatase (PPX), leading to lower phosphorus removal efficiency. However, the NH4+-N removal rates remained stable, and the removal efficiencies of TN increased due to the synthesis of nitrite and nitrous oxide (N2O) reductases. In addition, CuO NPs at concentrations of 0, 5, 20 mg/L increased the secretion of protein (PN) to 90, 91, 105 mg/gVSS, respectively, which could alleviate the toxicity of CuO NPs. High-throughput sequencing showed that CuO NPs increased the abundance of nitrogen-removal bacteria and reduced the abundance of phosphorus-removal bacteria, which is consistent with the results of pollutant removal upon long-term exposure to CuO NPs.

Targeted metabolomic study indicating glycyrrhizin's protection against acetaminophen-induced liver damage through reversing fatty acid metabolism.

The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen-induced liver toxicity. Seven-day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2- to 3-month-old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen-induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra-fast liquid chromatography coupled to triple time-of-flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin-treated, acetaminophen-treated, and glycyrrhizin+acetaminophen-treated groups. Long-chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long-chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen-induced liver damage through reversing fatty acid metabolism.

Biotransformation of glucoaurantio-obtusin towards aurantio-obtusin increases the toxicity of irinotecan through increased inhibition towards SN-38 glucuronidation.

The present study aims to investigate the influence of irinotecan's toxicity by the biotransformation of glucoaurantio-obtusin to aurantio-obtusin. Intraperitoneal administration (i.p.) of 100 mg/kg aurantio-obtusin significantly increased the toxicity of irinotecan, but the i.p. administration of 100 mg/kg glucoaurantio-obtusin showed negligible influence towards irinotecan's toxicity. Furthermore, the mechanism was explained through determining the inhibition potential of glucoaurantio-obtusin and aurantio-obtusin towards the glucuronidation metabolism of SN-38 that has been regarded to be the major active product responsible for the toxicity of irinotecan. The results showed that aurantio-obtusin exhibited strong competitive inhibition towards the glucuronidation of SN-38, but negligible inhibition potential of glucoaurantio-obtusin towards SN-38 glucuronidation was observed. These results showed that biotransformation of glucoaurantio-obtusin towards aurantio-obtusin increased the toxicity of irinotecan through increased inhibition of SN-38 glucuronidation.

In vitro characterization of glucuronidation of vanillin: identification of human UDP-glucuronosyltransferases and species differences.

Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP-glucuronosyltransferase conjugation pathway of vanillin was investigated in this study. Vanillin glucuronide was identified by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a hydrolysis reaction catalyzed by ß-glucuronidase. The kinetic study showed that vanillin glucuronidation by HLMs and HIMs followed Michaelis-Menten kinetics and the kinetic parameters were as follows: 134.9 ± 13.5 µM and 81.3 ± 11.3 µM for K(m) of HLMs and HIMs, 63.8 ± 2.0 nmol/min/mg pro and 13.4 ±2.0 nmol/min/mg pro for Vmax of HLMs and HIMs. All UDP-glucuronosyltransferase (UGT) isoforms except UGT1A4, 1A9, and 2B7 showed the capability to glucuronidate vanillin, and UGT1A6 exerted the higher V(max)/K(m) values than other UGT isoforms for the glucuronidation of vanillin when assuming expression of isoforms is similar in recombinant UGTs. Kinetic analysis using liver microsomes from six studied speices indicated that vanillin had highest affinity for the monkey liver microsomes enzyme (K(m) = 25.6 ± 3.2 µM) and the lowest affinity for the mice liver microsomes enzyme (K(m) = 149.1 ± 18.4 µM), and intrinsic clearance was in the following order: monkey > dog > minipig > mice > rat ~ human. These data collectively provided important information for understanding glucuronidation of vanillin.