Carbendazim (CBZ), a broad-spectrum pesticide frequently detected in fruits and vegetables, could trigger potential toxic risks to mammals. To facilitate the assessment of health risks, this study aimed to characterize the cytochrome P450 (CYPs)-mediated metabolism profiles of CBZ by a combined experimental and computational study. Our results demonstrated that CYPs-mediated region-selective hydroxylation was a major metabolism pathway for CBZ in liver microsomes from various species including rat, mouse, minipig, dog, rabbit, guinea pig, monkey, cow and human, and the metabolite was biosynthesized and well-characterized as 6-OH-CBZ. CYP1A displayed a predominant role in the region-selective hydroxylation of CBZ that could attenuate its toxicity through converting it into a less toxic metabolite. Meanwhile, five other common pesticides including chlorpyrifos-methyl, prochloraz, chlorfenapyr, chlorpyrifos, and chlorothalonil could significantly inhibit the region-selective hydroxylation of CBZ, and consequently remarkably increased CBZ exposure in vivo. Furthermore, computational study clarified the important contribution of the key amino acid residues Ser122, and Asp313 in CYP1A1, as well as Asp320 in CYP1A2 to the hydroxylation of CBZ through hydrogen bonds. These results would provide some useful information for the metabolic profiles of CBZ by mammalian CYPs, and shed new insights into CYP1A-mediated metabolic detoxification of CBZ and its health risk assessment.

Chromium (Cr) is an internationally recognized carcinogenic hazard that causes serious pulmonary toxicity. However, Cr-induced pulmonary toxicity lacks effective treatment to date. Sulforaphane (SFN), a well-known organosulfur compound, has gained increasing attention because of its unique biological function. This study investigates if SFN could decrease K₂Cr₂O₇-induced pulmonary toxicity and a potential mechanism involved using a rat 35-day Cr-induced pulmonary toxicity model and the mouse alveolar type II epithelial cell line (MLE-12). The results showed that SFN prevented Cr-induced oxidative stress, histopathological lesions, inflammation, apoptosis, and changes in protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK-3β) levels in vivo and in vitro. However, SFN can not play the protective effect against K₂Cr₂O₇-induced cell injury after treating by an Akt-specific inhibitor (MK-2206 2HCl) in MLE-12 cells. Furthermore, SFN increased the expression of nuclear factor-E2-related factor-2 (Nrf2) phase II detoxification enzymes. Collectively, this study demonstrates that SFN prevents K₂Cr₂O₇-induced lung toxicity in rats through enhancing Nrf2-mediated exogenous antioxidant defenses via activation of the Akt/GSK-3β/Fyn signaling pathway. SFN may be a novel natural substance to cure Cr-induced lung toxicity.

Ochratoxin A (OTA) is a potent mycotoxin that frequently contaminates agro-products and threatens food safety. A highly efficient OTA degrading strain Lysobacter sp. CW239 was isolated, and the OTA degradation characteristics were investigated. A novel OTA degrading gene carboxypeptidase cp4 was successfully cloned and characterized from CW239. The heterologous recombinant was constructed by gene cp4 and expression vector pET-32a⁽⁺⁾ and overexpressed by E. coli BL21 CodonPlus™ (DE3). The recombinant protein rCP4 was purified, and the OTA-degrading activity was evaluated. Although OTA was efficiently degraded by CW239 (24-h degradation ratio of 86.2%), the 24-h OTA degradation ratio for rCP4 was only 36.8% at fairly high concentration (0.25 mg/mL) protein. The degraded product was obtained by immune affinity column (IAC) and determined by mass spectrometry (MS), and the degraded product was the less toxic ochratoxin α (OTα). Based on the serial investigations of this study, OTA might be simultaneously co-degraded by CP4 and another unknown degrading agent in that degrading strain.

Atrazine (ATR), one of the most widely used pesticides in agricultural production, are gradually concerned due to potential ecosystem and health risks. Further, the induction of ATR nephrotoxicity and detoxification response is still unknown. To evaluate ATR-induced nephrotoxicity, quails were treated with 0, 50, 250 or 500 mg/kg ATR by gavage administration for 45 days. Histopathology indicated that ATR exposure caused renal tubular epithelial cell swelling and endoplasmic reticulum degeneration, suggesting that ATR exposure causes renal impairment even renal diseases. Notably, ATR interfered cytochrome P450 system (CYP450s) homeostasis by enhancing contents or activities of CYP450s (total CYP450, Cyt b5, AH, APND, NCR and ERND) and the expression of CYP450 isoforms (CYP1A, CYP1B, CYP2C and CYP3A). ATR triggered phase II detoxifying reaction, reflected by the elevated GSH level, GST activity and the up-regulation of GST isoforms (GSTa, GSTa3 and GSTt1) and GSH synthetase (GCLC). Moreover, ABC transporters were activated to expel ATR from the body by increasing expression of MRP1 and P-GP gene. Accompanying these alterations, the nuclear receptors (AHR, CAR and PXR) were activated by ATR in a dose-dependent manner. Analysis results of present study demonstrated that the induction of phase II detoxifying enzyme system and ABC transporters could be modulated by nuclear receptors response and CYP450s disturbance in low-dose ATR-treated quail. In conclusion, all data suggested that nuclear receptors AHR-mediated detoxification pathway was involved in ATR-induced nephrotoxicity. These results provided new evidence about the nephrotoxic effects of ATR on the response of biotransformation and detoxification system.

Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM.

Mercury (Hg) is a global pollutant that poses a serious threat to human and the environment. Rice was found as an important source for human exposure to Hg in some areas. In this study, the transportation and transformation of IHg and MeHg in rice plants exposed to IHg or MeHg were investigated. The IHg and MeHg concentrations in rice roots and shoots collected every five days were analyzed by HPLC-ICP-MS and SR-XANES. When exposed to MeHg, the percent of IHg in rice roots and shoots increased while MeHg decreased significantly, suggesting prominent demethylation of MeHg occurred. However no notable MeHg was found in both roots and shoots of rice plant when exposed to IHg. SR-XANES analysis further confirmed the demethylation of MeHg with rice. This study provides a new finding that demethylation of MeHg could occur in growing rice, which may be a self-defense process of rice plant.

Novel magnetic microcomposites consisting of graphene oxide and iron oxide was synthesized to immobilize metabolically versatile Paracoccus sp. MKU1 and Leucobacter sp. AA7 and tested for the simultaneous adsorption and enhanced biological detoxification of hexavalent chromium (Cr(VI)) from tannery wastewater. This study reports highest chromium adsorption of 272.6 mg/g and 179.3 mg/g with complete reduction of Cr(VI) to Cr(III) by the microcomposites of AA7 and MKU1 from wastewater in a bioreactor (10 L) at large-scale for first time in ex situ. Furthermore, both the microcomposites displayed an enhanced detoxification of tannery wastewater by reducing various physicochemical conditions such as ammonia, nitrate, TDS, fluoride, CaCO₃, Ca, Mg, NO₃ and SO₂ under the permissible limits. Use of electromagnetic device for magnetic microcomposites recovery from bioreactor yielded a maximum of 88% and 80.6% recovery for AA7 and MKU1, respectively. The rate of chromium recuperation achieved following desorption from the microcomposites of AA7 and MKU1 was 90.71% and 93.97%, respectively. Thus, the multifarious benefits including adsorption, metabolic detoxification, recovery, and recuperation by single functional microcomposites seems to be an intriguing and profitable approach for practicing in real-time operations to effectively remove heavy metals from the contaminated wastewater for environmental protection.

Cadmium (Cd) is a toxic metal that contributes to human diseases such as pediatric cancer and cardiovascular dysfunction. Epigenetic modification caused by Cd exposure is the major factor in etiology of environmentally-relevant diseases. However, the underlying epigenetic mechanism for Cd uptake and accumulation in food crops, particularly those growing in Cd-contaminated environments, is largely unknown. This study investigated uncharacterized regulatory mechanisms and biological functions of global DNA hypomethylation at CG sites that are associated with gene expression for Cd detoxification and accumulation in the food crop rice. Mutation of the CG maintenance enzyme OsMET1 confers rice tolerance to Cd exposure. Genome-wide analysis of OsMET1 loss of function mutant Osmet1 and its wild type shows numerous loci differentially methylated and upregulated genes for Cd detoxification, transport and accumulation. We functionally identified a new locus for a putative cadmium tolerance factor (here termed as OsCTF) and demonstrated that Cd-induced DNA demethylation is the drive of OsCTF expression. The 3′-UTR of OsCTF is the primary site of DNA and histone (H3K9me2) demethylation, which is associated with higher levels of OsCTF transcripts detected in the Osmet1 and Ossdg714 mutant lines. Mutation of OsCTF in rice led to hypersensitivity to Cd and the Osctf line accumulated more Cd, whereas transfer of OsCTF back to the Osctf mutant completely restored the normal phenotype. Our work unveiled an important epigenetic mechanism and will help develop breeding crops that contribute to food security and better human health.

Pteris vittata is known to hyperaccumulate As but the mechanism is poorly understood. We found an increase of As concentration with increasing soil solution As concentrations, but P application had no impact, although plant P concentrations responded to different rates of P supply. As in fronds was dominantly (82-89%) present in the form of AsIII. In roots we detected 45% as AsIII which is higher than reported in previous studies and supports substantial As-reduction to take place in roots. We detected PC2/3GS-AsIII, PC2-GS-AsIII and (PC2)2-AsIII in increasing amounts with application of As. The total amount of PC was in the range reported previously and far too small to assign a significant role in As detoxification to PCs. The close correlation between S and As in fronds and the lack of data on sulphur uptake and metabolism indicates the need for a detailed investigation on sulphur nutritional status and As metabolism in P. vittata. As-PC complexes were detected in increasing amounts with increasing As availability, but total amounts were small and do not explain the close correlation between S and As in fronds.