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Regioselective hydroxylation of carbendazim by mammalian cytochrome P450: A combined experimental and computational study
2022
Lv, Xia | Li, Jing-Xin | Wang, Jia-Yue | Tian, Xiang-Ge | Feng, Lei | Sun, Cheng-Peng | Ning, Jing | Wang, Chao | Zhao, Wen-Yu | Li, Ya-Chen | Ma, Xiao-Chi
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.
显示更多 [+] 显示较少 [-]Inhalation of concentrated PM2.5 from Mexico City acts as an adjuvant in a guinea pig model of allergic asthma
2017
Falcon-Rodriguez, Carlos Iván | De Vizcaya-Ruiz, Andrea | Rosas-Pérez, Irma Aurora | Osornio-Vargas, Álvaro Román | Segura-Medina, Patricia
Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 μg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased ∼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (∼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and β-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway inflammation. Fine particles from Mexico City is a complex mix, which play a significant role as adjuvant in allergic asthma.
显示更多 [+] 显示较少 [-]Evaluation of methane production from the anaerobic co-digestion of manure of guinea pig with lignocellulosic Andean residues
2022
Meneses Quelal, Washington Orlando | Velázquez Martí, Borja | Gaibor Chávez, Juan | Niño Ruiz, Zulay | Ferrer Gisbert, Andrés
The objective of this research was to evaluate anaerobic co-digestion of guinea pig manure (GP) with Andean agricultural residues such as amaranth (AM), quinoa (QU) and wheat (TR) in batch biodigesters under mesophilic conditions (37 ⁰C) for 40 days. As microbial inoculum, sewage treatment sludge was used in two inoculum/substrate ratios (ISR of 1 and 2). In terms of methane production, the best results occurred in treatments containing AM and QU as co-substrate and an ISR of 2. Thus, the highest methane production yield in the GP:AM biodigesters (25:75) and GP:QU (25:75) with 341.86 mlCH₄/g VS added and 341.05 mlCH₄/g VS added, respectively. On the other hand, the results showed that methane production with an ISR of 2 generated higher yields for guinea pig waste and the methane fraction of the biogas generated was in a range from 57 to 69%. Methane production kinetics from these raw materials was studied using five kinetic models: modified Gompertz, logistic equation, transfer, cone and Richards. The cone model adjusted best to the experimental values with those observed with r² of 0.999 and RMSE of 1.16 mlCH₄/g VS added. Finally, the highest biodegradability (experimental yield/theoretical yield) was obtained in the GP-AM biodigesters (25:75) with 67.92%.
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