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Environmental Health Perspectives Oct 1994Acetylation by arylamine N-acetyltransferases (NATs) is a major route in the metabolism of numerous drugs and carcinogens. Recent studies suggest that the same enzymes...
Acetylation by arylamine N-acetyltransferases (NATs) is a major route in the metabolism of numerous drugs and carcinogens. Recent studies suggest that the same enzymes also catalyze N,O-transacetylation and O-acetylation. A genetic polymorphism of clinical relevance divides the human population into slow and rapid acetylators of arylamines. Two human NATs, NAT1 and NAT2, have recently been characterized by protein purification, cloning, and functional expression of the respective genes; both were localized to chromosome 8. NAT1 codes for a protein with ubiquitous tissue distribution and a high affinity for p-aminobenzoic acid and p-aminosalicylic acid, so-called monomorphic substrates. NAT2 codes for a protein predominantly expressed in liver with a high affinity for sulfamethazine and other polymorphically metabolized drugs. NAT2 was analyzed at the level of protein, RNA and DNA derived from phenotyped slow and rapid acetylators. Two common (M1, M2) and one rare (M3) mutant allele were identified and their mutations characterized. A simple polymerase chain reaction-based DNA test can identify > 95% of mutant alleles and predict the phenotype.
Topics: Acetylation; Acetyltransferases; Animals; Cloning, Molecular; Genotype; Humans; Mutation; Phenotype; Polymorphism, Genetic; Rabbits
PubMed: 7889851
DOI: 10.1289/ehp.94102s6213 -
Scientific Reports Sep 2021A new series of nucleosides, moieties, and Schiff bases were synthesized from sulfadimidine. Infrared (IR), HNMR, C NMR, and mass spectrometry techniques and elemental...
A new series of nucleosides, moieties, and Schiff bases were synthesized from sulfadimidine. Infrared (IR), HNMR, C NMR, and mass spectrometry techniques and elemental analysis were employed to elucidate the synthesized compounds. The prepared analogues were purified by different chromatographic techniques (preparative TLC and column chromatography). Molecular docking studies of synthesized compounds 3a, 4b, 6a, and 6e demonstrated the binding mode involved in the active site of DNA gyrase. Finally, all synthesized compounds were tested against selected bacterial strains. The most effective synthesized compounds against S. aureus were 3a, 4d, 4b, 3b, 3c, 4c, and 6f, which exhibited inhibition zones of inhibition of 24.33 ± 1.528, 24.67 ± 0.577, 23.67 ± 0.577, 22.33 ± 1.528, 18.67 ± 1.528 and 19.33 ± 0.577, respectively. Notably, the smallest zones were observed for 4a, 6d, 6e and 6g (6.33 ± 1.528, 11.33 ± 1.528, 11.67 ± 1.528 and 14.66 ± 1.155, respectively). Finally, 6b and 6c gave negative zone values. K. pneumoniae was treated with the same compounds and the following results were obtained. The most effective compounds were 4d, 4c, 4b and 3c, which showed inhibition zones of 29.67 ± 1.528, 24.67 ± 0.577, 23.67 ± 1.155 and 19.33 ± 1.528, respectively, followed by 4a and 3d (15.33 ± 1.528 for both), while moderate results (13.67 ± 1.155 and 11.33 ± 1.528) were obtained for 6f and 6g, respectively. Finally, 6a, 6b, 6c, 3a, and 3b did not show any inhibition. The most effective compounds observed for the treatment of E. coli were 4d, 4b, 4c, 3d, 6e and 6f (inhibition zones of 26.33 ± 0.577, 21.67 ± 1.528, 21.67 ± 1.528, 19.67 ± 1.528, 17.67 ± 1.155 and 16.67 ± 1.155, respectively). Compounds 3b, 3c, 6a, 6c, and 6g gave moderate results (13.67 ± 1.528, 12.67 ± 1.528, 11.33 ± 0.577, 15.33 ± 1.528 and 12.67 ± 1.528, respectively), while 6b showed no effect. The MIC values against S. aureus ranged from 50 to 3.125 mg, while those against E. coli and K. pneumoniae ranged from 50 to 1562 mg. In vitro, the antibacterial effects were promising. Further research is required to study the in vivo antibacterial effects of these compounds and determine therapeutic doses.
Topics: Anti-Bacterial Agents; Catalytic Domain; DNA Gyrase; Escherichia coli; Hydrogen Bonding; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Docking Simulation; Nucleosides; Schiff Bases; Staphylococcus aureus; Structure-Activity Relationship; Sulfamethazine
PubMed: 34504157
DOI: 10.1038/s41598-021-97297-1 -
Environmental Health Perspectives Feb 1997
Topics: Animals; Anti-Infective Agents; Birth Weight; Body Weight; Dose-Response Relationship, Drug; Female; Fertility; Litter Size; Liver; Male; Mice; Organ Size; Pregnancy; Reproduction; Seminal Vesicles; Sulfamethazine
PubMed: 9114356
DOI: No ID Found -
The Journal of Antimicrobial... Sep 2023Resistance genes can be genetically transmitted and exchanged between commensal and pathogenic bacterial species, and in different compartments including the...
OBJECTIVES
Resistance genes can be genetically transmitted and exchanged between commensal and pathogenic bacterial species, and in different compartments including the environment, or human and animal guts (One Health concept). The aim of our study was to evaluate whether subdosages of antibiotics administered in veterinary medicine could enhance plasmid transfer and, consequently, resistance gene exchange in gut microbiota.
METHODS
Conjugation frequencies were determined with Escherichia coli strains carrying IncL- (blaOXA-48) or IncI1-type (blaCTX-M-1) plasmids subjected to a series of subinhibitory concentrations of antibiotics used in veterinary medicine, namely amoxicillin, ceftiofur, apramycin, neomycin, enrofloxacin, colistin, erythromycin, florfenicol, lincomycin, oxytetracycline, sulfamethazine, tiamulin and the ionophore narasin. Treatments with subinhibitory dosages were performed with and without supplementation with the antioxidant edaravone, known as a mitigator of the inducibility effect of several antibiotics on plasmid conjugation frequency (PCF). Expression of SOS-response associated genes and fluorescence-based reactive oxygen species (ROS) detection assays were performed to evaluate the stress oxidative response.
RESULTS
Increased PCFs were observed for both strains when treating with florfenicol and oxytetracycline. Increased expression of the SOS-associated recA gene also occurred concomitantly, as well as increased ROS production. Addition of edaravone to the treatments reduced their PCF and also showed a decreasing effect on SOS and ROS responses for both plasmid scaffolds.
CONCLUSIONS
We showed here that some antibiotics used in veterinary medicine may induce transfer of plasmid-encoded resistance and therefore may contribute to the worldwide spread of antibiotic resistance genes.
Topics: Animals; Humans; Anti-Bacterial Agents; Oxytetracycline; Edaravone; Reactive Oxygen Species; Escherichia coli; Plasmids; Drug Resistance, Microbial; Gene Transfer, Horizontal
PubMed: 37486104
DOI: 10.1093/jac/dkad226 -
International Journal of Environmental... Mar 2022Four types of tourmalines (TMs, S1, S2, S3 and S4) for activating persulfate (PS) to degrade sulfamethazine (SMT) were compared to find the most efficient catalyst. The...
Four types of tourmalines (TMs, S1, S2, S3 and S4) for activating persulfate (PS) to degrade sulfamethazine (SMT) were compared to find the most efficient catalyst. The four TMs were mesoporous materials with abundant functional groups, but were different in terms of size, composition, specific surface area, contact angle, and zero potential point. The removal of SMT in S1, S2, S3 and S4 systems with PS at the optimum reaction conditions ([SMT] = 5 mg/L, [PS] = 4 mM, [TM] = 5 g/L, pH = 5, and T = 25 °C) were 99.0%, 25.5%, 26.0%, and 51.0%, respectively, which might be related to the metal content of TM. Although the degradation of SMT in the S1/PS/SMT system was not dominated by SO and •OH, the radicals contributed to the SMT removal in the S2, S3, and S4 systems. O and holes both contributed to the degradation of SMT in the four systems. The metal at the X position might be related to the generation of O and holes, while Fe of TM was mainly related to the generation of free radicals, such as SO. Electrochemical impedance spectroscopy tests confirmed that the separation of electrons and holes on the TM surface could be promoted by adding PS and SMT. S1 presented a higher electron-transfer rate than the other three TMs. The PS activation by TM with a high metal content at the X position provided an efficient and low-consumption treatment for antibiotic refractory wastewater.
Topics: Hydrogen Peroxide; Kinetics; Sulfamethazine; Wastewater; Water Pollutants, Chemical
PubMed: 35328932
DOI: 10.3390/ijerph19063244 -
Scientific Reports Aug 2022Photocatalysis process is a promising technology for environmental remediation. In the continuous search of new heterogeneous photocatalysts, metal-organic frameworks...
Photocatalysis process is a promising technology for environmental remediation. In the continuous search of new heterogeneous photocatalysts, metal-organic frameworks (MOFs) have recently emerged as a new type of photoactive materials for water remediation. Particularly, titanium-based MOFs (Ti-MOFs) are considered one of the most appealing subclass of MOFs due to their promising optoelectronic and photocatalytic properties, high chemical stability, and unique structural features. However, considering the limited information of the reported studies, it is a hard task to determine if real-world water treatment is attainable using Ti-MOF photocatalysts. In this paper, via a screening with several Ti-MOFs, we originally selected and described the potential of a Ti-MOF in the photodegradation of a mixture of relevant Emerging Organic Contaminants (EOCs) in real water. Initially, two challenging drugs (i.e., the β-blocker atenolol (At) and the veterinary antibiotic sulfamethazine (SMT)) and four water stable and photoactive Ti-MOF structures have been rationally selected. From this initial screening, the mesoporous Ti-trimesate MIL-100(Ti) was chosen as the most promising photocatalyst, with higher At or SMT individual photodegradation (100% of At and SMT photodegradation in 2 and 4 h, respectively). Importantly, the safety of the formed by-products from the At and SMT photodegradation was confirmed. Finally, the At and SMT photodegradation capacity of MIL-100(Ti) was confirmed under realistic conditions, by using a mixture of contaminants in tap drinking water (100% of At and SMT photodegradation in 4 h), proven in addition its potential recyclability, which reinforces the potential of MIL-100(Ti) in water remediation.
Topics: Metal-Organic Frameworks; Photolysis; Sulfamethazine; Titanium; Water Purification
PubMed: 36008470
DOI: 10.1038/s41598-022-18590-1 -
Toxicology and Applied Pharmacology May 2022Lung cancer is the leading cause of cancer deaths in the United States with high incidence in tobacco smokers. Arylamine N-acetyltransferase 2 (NAT2) is a xenobiotic...
Lung cancer is the leading cause of cancer deaths in the United States with high incidence in tobacco smokers. Arylamine N-acetyltransferase 2 (NAT2) is a xenobiotic enzyme that catalyzes both N- and O-acetylation of carcinogens present in tobacco smoke and contributes towards the genotoxicity of these carcinogens. NAT2 allelic variants result in slow, intermediate, and rapid acetylation phenotypes. A recent meta-analysis reported NAT2 non-rapid (slow and intermediate) phenotypes had a significantly increased risk of lung cancer. NAT2 activity in humans is thought to be restricted to liver and gastrointestinal tract, and no studies to our knowledge have reported the expression of NAT2 activity in immortalized human lung epithelial cells. Given the importance of NAT2 in cancer and inhalation of various carcinogens directly into the lungs, we investigated NAT2 activity in human lung epithelial cells. Both NAT1 and NAT2 protein were detected by "in-cell" Western. Arylamine N-acetyltransferase activity was determined with selective substrates for NAT1 (p-aminobenzoic acid; PABA) and NAT2 (sulfamethazine; SMZ) in the presence and absence of a selective NAT1 inhibitor. PABA N-acetylation (NAT1 activity) in cell protein lysates was abolished in the presence of 25 μM of NAT1 inhibitor whereas SMZ N-acetylation (NAT2) was unaffected. Incubation with the NAT1 inhibitor partially reduced the N-acetylation of β-naphthylamine and the O-acetylation of N-hydroxy-4-aminobiphenyl consistent with catalysis by both NAT1 and NAT2. Immortalized human lung epithelial cells exhibited dose-dependent N-acetylation of 4-ABP with an apparent K of 24.4 ± 5.1 μM. These data establish that NAT2 is expressed and functional in immortalized human lung epithelial cells and will help us further our understanding of NAT2 in lung cancer.
Topics: 4-Aminobenzoic Acid; Acetylation; Arylamine N-Acetyltransferase; Carcinogens; Epithelial Cells; Humans; Isoenzymes; Lung Neoplasms
PubMed: 35353990
DOI: 10.1016/j.taap.2022.115993 -
Scientific Reports Sep 2017Activated carbon (AC) was modified by FeCl. Batch experiments were carried out to evaluate the characteristics of equilibrium, kinetics and thermodynamics of...
Activated carbon (AC) was modified by FeCl. Batch experiments were carried out to evaluate the characteristics of equilibrium, kinetics and thermodynamics of Sulfamethazine adsorption onto original and modified AC. The results showed that Fe treatment changed the surface area, pore volume and surface zeta potential and increased the number of surface oxygenic functional groups. The adsorption of Sulfamethazine on modified activated carbon (MAC) was significantly improved. Isotherm test results revealed that the adsorption isotherms of Sulfamethazine on MAC fit the Freundlich, Langmuir and Temkin equations well. The maximum adsorption quantity of Sulfamethazine on MAC was 17.2414 mg/g at 25 °C. The adsorption kinetics of Sulfamethazine on AC and MAC can be characterized by the pseudo-second-order model. The adsorption process was affected by membrane diffusion, surface adsorption and internal diffusion. The adsorption quantities of Sulfamethazine first increased and then decreased for pH between 3 and 10. The removal efficiencies decreased with increasing temperature, which is favorable for adsorption at low temperature. It was also found that the mechanisms of adsorption included micropore capture and electrostatic, hydrogen bonding, π-π electron donor-acceptor (EDA) and coordination interactions as well as other interactions.
PubMed: 28963547
DOI: 10.1038/s41598-017-12805-6 -
FEMS Microbiology Ecology Jun 2023Microbacterium sp. C448, isolated from a soil regularly exposed to sulfamethazine (SMZ), can use various sulphonamide antibiotics as the sole carbon source for growth....
Effect of subtherapeutic and therapeutic sulfamethazine concentrations on transcribed genes and translated proteins involved in Microbacterium sp. C448 resistance and degradation.
Microbacterium sp. C448, isolated from a soil regularly exposed to sulfamethazine (SMZ), can use various sulphonamide antibiotics as the sole carbon source for growth. The basis for the regulation of genes encoding the sulphonamide metabolism pathway, the dihydropteroate synthase sulphonamide target (folP), and the sulphonamide resistance (sul1) genes is unknown in this organism. In the present study, the response of the transcriptome and proteome of Microbacterium sp. C448 following exposure to subtherapeutic (33 µM) or therapeutic (832 µM) SMZ concentrations was evaluated. Therapeutic concentration induced the highest sad expression and Sad production, consistent with the activity of SMZ degradation observed in cellulo. Following complete SMZ degradation, Sad production tended to return to the basal level observed prior to SMZ exposure. Transcriptomic and proteomic kinetics were concomitant for the resistance genes and proteins. The abundance of Sul1 protein, 100-fold more abundant than FolP protein, did not change in response to SMZ exposure. Moreover, non-targeted analyses highlighted the increase of a deaminase RidA and a putative sulphate exporter expression and production. These two novel factors involved in the 4-aminophenol metabolite degradation and the export of sulphate residues formed during SMZ degradation, respectively, provided new insights into the Microbacterium sp. C448 SMZ detoxification process.
Topics: Microbacterium; Sulfamethazine; Soil Microbiology; Biodegradation, Environmental; Kinetics; Transcriptome; Proteome; Sulfonamides; Drug Resistance, Bacterial; Anti-Infective Agents; Mixed Function Oxygenases; Dihydropteroate Synthase
PubMed: 37309049
DOI: 10.1093/femsec/fiad064 -
ACS Omega Aug 2023In this study, a composite of pond mud and lanthanum- and nano-zero valent iron-modified-biochar was investigated for its ability to adsorb methylene blue (MB) and...
In this study, a composite of pond mud and lanthanum- and nano-zero valent iron-modified-biochar was investigated for its ability to adsorb methylene blue (MB) and sulfamethazine (SMZ). La-modified attapulgite and nano-zero valent iron (surface area enhanced by 43.7% via Brunauer-Emmett-Teller analysis) were successfully loaded onto the straw-sediment biochar (BC) surface. With the increase in pyrolysis temperature, the biocompatibility yield, the H, O, and N content, and the ratio of carbon elements decreased, while the pH value, surficial micropores, C element, and ash content increased. The biocarbon small molecules were gradually and tightly ordered, and the organic groups such as hydroxyl, carboxyl groups, and carbon oxygen double bonds were gradually lost or disappeared. The original Fe-BC had more phenolic hydroxyl groups forming an intermolecular hydrogen bond than others with a higher adsorption capacity possibly through the Schiff base reaction. The effect of various pH (2-9), temperature (15-35 °C), and initial concentration (1-25 mg L) on adsorption was investigated. pH and temperature were the main factors governing the adsorption process. The maximum adsorption capacity was observed at pH 4. The adsorption performances for MB followed the order Fe-BC > La-BC > BC, and the maximum removal rate was over 98.45% with pH = 7. The three types of BC dosages between 0.2 (6.67 g L) and 0.4 g showed a removal rate of 99% for MB. The adsorption capacity of Fe-BC, La-BC, and BC for MB was 2.201, 1.905, and 2.401 mg L with pH = 4, while 4.79, 4.58, and 5.55 mg g were observed with BC dosage at 0.025 g. For SMZ, the higher the temperature, the better the adsorption effect, and it reaches saturation at approximately 25 °C. To further evaluate the nature of adsorption, Langmuir/Freundlich/Temkin models were tested and the adsorption capacities were evaluated on the surface of the BC composite. The three modified materials were physisorbed to SMZ, while MB was chemisorbed. For MB, the adsorption performance of BC is the best < 0.2 g (6.67 g L) at pH 7.0 at 35 °C. The Elovich model was more suitable for MB, while the Freundlich and Temkin models could better fit the adsorption process of MB. The preparatory secondary dynamics equation and Langmuir equation were more compliant for SMZ, and the saturated adsorption capacities of straw-modified, La-BC, and Fe-BC reached 5.699, 6.088, and 5.678 mg L, respectively.
PubMed: 37636932
DOI: 10.1021/acsomega.3c01251