{"title":"Analysis of the vibrioferrin biosynthetic pathway of Vibrio parahaemolyticus","authors":"Tomotaka Tanabe, Hidemichi Mitome, Katsushiro Miyamoto, Kazuki Akira, Hiroshi Tsujibo, Koji Tomoo, Kenjiro Nagaoka, Tatsuya Funahashi","doi":"10.1007/s10534-023-00566-x","DOIUrl":"10.1007/s10534-023-00566-x","url":null,"abstract":"<div><p>Siderophores are small-molecule iron chelators produced by many microorganisms that capture and uptake iron from the natural environment and host. Their biosynthesis in microorganisms is generally performed using non-ribosomal peptide synthetase (NRPS) or NRPS-independent siderophore (NIS) enzymes. <i>Vibrio parahaemolyticus</i> secretes its cognate siderophore vibrioferrin under iron-starvation conditions. Vibrioferrin is a dehydrated condensate composed of α-ketoglutarate, L-alanine, aminoethanol, and citrate, and <i>pvsA</i> (the gene encoding the ATP-grasp enzyme), <i>pvsB</i> (the gene encoding the NIS enzyme), <i>pvsD</i> (the gene encoding the NIS enzyme), and <i>pvsE</i> (the gene encoding decarboxylase) are engaged in its biosynthesis. Here, we elucidated the biosynthetic pathway of vibrioferrin through in vitro enzymatic reactions using recombinant PvsA, PvsB, PvsD, and PvsE proteins. We also found that PvsD condenses L-serine and citrate to generate <i>O</i>-citrylserine, and that PvsE decarboxylates <i>O</i>-citrylserine to form <i>O</i>-citrylaminoethanol. In addition, we showed that <i>O</i>-citrylaminoethanol is converted to alanyl-<i>O</i>-citrylaminoethanol by amidification with L-Ala by PvsA and that alanyl-<i>O</i>-citrylaminoethanol is then converted to vibrioferrin by amidification with α-ketoglutarate by PvsB.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"507 - 517"},"PeriodicalIF":4.1,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometalsPub Date : 2023-12-22DOI: 10.1007/s10534-023-00572-z
Marthe K. Charles, Teresa C. Williams, Davood Nakhaie, Tracey Woznow, Billie Velapatino, Ana C. Lorenzo-Leal, Horacio Bach, Elizabeth A. Bryce, Edouard Asselin
{"title":"In vitro assessment of antibacterial and antiviral activity of three copper products after 200 rounds of simulated use","authors":"Marthe K. Charles, Teresa C. Williams, Davood Nakhaie, Tracey Woznow, Billie Velapatino, Ana C. Lorenzo-Leal, Horacio Bach, Elizabeth A. Bryce, Edouard Asselin","doi":"10.1007/s10534-023-00572-z","DOIUrl":"10.1007/s10534-023-00572-z","url":null,"abstract":"<div><p>Copper has well-documented antibacterial effects but few have evaluated it after prolonged use and against bacteria and viruses. Coupons from three copper formulations (solid, thermal coating, and decal applications) and carbon steel controls were subjected to 200 rounds simulated cleaning using a Wiperator™ and either an accelerated hydrogen peroxide, quaternary ammonium, or artificial sweat products. Antibacterial activity against <i>S. aureus</i> and <i>P. aeruginosa</i> was then evaluated using a modified Environmental Protection Agency protocol. Antiviral activity against coronavirus (229E) and norovirus (MNV-1) surrogates was assessed using the TCID<sub>50</sub> method. Results were compared to untreated control coupons. One hour after inoculation, <i>S. aureus</i> exhibited a difference in log kill of 1.16 to 4.87 and <i>P. aeruginosa</i> a log kill difference of 3.39–5.23 (dependent upon copper product and disinfectant) compared to carbon steel. MNV-1 demonstrated an 87–99% reduction on each copper surfaces at 1 h and 99% reduction at 2 h compared to carbon steel. Similarly, coronavirus 229E exhibited a 97–99% reduction after 1 h and 90–99% after 2 h. Simulated use with artificial sweat did not hinder the antiviral nor the antibacterial activity of Cu surfaces. Self-sanitizing copper surfaces maintained antibacterial and antiviral activity after 200 rounds of simulated cleaning. </p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 4","pages":"849 - 856"},"PeriodicalIF":4.1,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Consumption of chewing tobacco alters the serum metal contents in pregnant women at Tandojam and adjoining areas","authors":"Amna Yasin Awan, Naseem Aslam Channa, Shazia Perveen Solangi, Lubna Noorani","doi":"10.1007/s10534-023-00571-0","DOIUrl":"10.1007/s10534-023-00571-0","url":null,"abstract":"<div><p>Chewing tobacco may play a contributing role in complications during pregnancy as it contains various kinds of toxic metals such as lead (Pb), cadmium (Cd), cobalt (Co), manganese (Mn), chromium (Cr), and can cause alteration in serum metal concentration. Hence, the present study aimed to explore the effects of chewing tobacco consumption on serum metal contents in pregnant women. A total number of 200 chewing tobacco consumer pregnant women and 200 age-matched non-consumer pregnant women were selected for the study from the outpatient department of gynaecology at Rural Health Centre Tandojam, Pakistan. After obtaining the sociodemographic characteristics of all participants, 10 ml of venous blood was also drawn for serum metal analysis by atomic absorption spectroscopy. Different chewing tobacco samples consumed by consumer pregnant women were collected from local shops of Tandojam, Pakistan. Drinking water samples from the residential areas of consumer and non-consumer pregnant women were prepared and analysed for the same metal contents. In present study, serum Pb, Cd, K and Co were found significantly increased in CPW as compared to NCPW. Serum Pb was found significantly increased in gutkha consumers in comparison to mainpuri consumers. Serum Pb, Cd, and Co were present with significantly increased concentration in serum of CPW who were taking canal and well water for drinking purpose when compared with NCPW. Significant negative strong correlation of serum Pb with K and Cr of drinking water and Na of chewing tobacco samples were observed. Strong positive correlation of serum Cd and Cr with Co of drinking water had been observed. Whereas, serum maternal Co was strongly negatively correlated with Mn of chewing tobacco samples, and serum Cu of CPW had a strong positive correlation with K and Cr of drinking water and Na of chewing tobacco samples. In conclusion, consumption of chewing tobacco alters the serum metal contents in pregnant women at Tandojam and adjoining areas, Pakistan.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 4","pages":"839 - 847"},"PeriodicalIF":4.1,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometalsPub Date : 2023-12-19DOI: 10.1007/s10534-023-00565-y
Raymond J. Turner
{"title":"The good, the bad, and the ugly of metals as antimicrobials","authors":"Raymond J. Turner","doi":"10.1007/s10534-023-00565-y","DOIUrl":"10.1007/s10534-023-00565-y","url":null,"abstract":"<div><p>We are now moving into the antimicrobial resistance (AMR) era where more antibiotic resistant bacteria are now the majority, a problem brought on by both misuse and over use of antibiotics. Unfortunately, the antibiotic development pipeline dwindled away over the past decades as they are not very profitable compounds for companies to develop. Regardless researchers over the past decade have made strides to explore alternative options and out of this we see revisiting historical infection control agents such as toxic metals. From this we now see a field of research exploring the efficacy of metal ions and metal complexes as antimicrobials. Such antimicrobials are delivered in a variety of forms from metal salts, alloys, metal complexes, organometallic compounds, and metal based nanomaterials and gives us the broad term metalloantimicrobials. We now see many effective formulations applied for various applications using metals as antimicrobials that are effective against drug resistant strains. The purpose of the document here is to step aside and begin a conversation on the issues of use of such toxic metal compounds against microbes. This critical opinion mini-review in no way aims to be comprehensive. The goal here is to understand the benefits of metalloantimicrobials, but also to consider strongly the disadvantages of using metals, and what are the potential consequences of misuse and overuse. We need to be conscious of the issues, to see the entire system and affect through a OneHealth vision.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 3","pages":"545 - 559"},"PeriodicalIF":4.1,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-023-00565-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometalsPub Date : 2023-12-18DOI: 10.1007/s10534-023-00562-1
Maria Gracheva, Zoltán Klencsár, Zoltán Homonnay, Ádám Solti, László Péter, Libor Machala, Petr Novak, Krisztina Kovács
{"title":"Revealing the nuclearity of iron citrate complexes at biologically relevant conditions","authors":"Maria Gracheva, Zoltán Klencsár, Zoltán Homonnay, Ádám Solti, László Péter, Libor Machala, Petr Novak, Krisztina Kovács","doi":"10.1007/s10534-023-00562-1","DOIUrl":"10.1007/s10534-023-00562-1","url":null,"abstract":"<div><p>Citric acid plays an ubiquitous role in the complexation of essential metals like iron and thus it has a key function making them biologically available. For this, iron(III) citrate complexes are considered among the most significant coordinated forms of ferric iron that take place in biochemical processes of all living organisms. Although these systems hold great biological relevance, their coordination chemistry has not been fully elucidated yet. The current study aimed to investigate the speciation of iron(III) citrate using Mössbauer and electron paramagnetic resonance spectroscopies. Our aim was to gain insights into the structure and nuclearity of the complexes depending on the pH and iron to citrate ratio. By applying the frozen solution technique, the results obtained directly reflect the iron speciation present in the aqueous solution. At 1:1 iron:citrate molar ratio, polynuclear species prevailed forming most probably a trinuclear structure. In the case of citrate excess, the coexistence of several monoiron species with different coordination environments was confirmed. The stability of the polynuclear complexes was checked in the presence of organic solvents.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"461 - 475"},"PeriodicalIF":4.1,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-023-00562-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometalsPub Date : 2023-12-12DOI: 10.1007/s10534-023-00561-2
Rafia Shah, Feriha Fatima Khidri, Yar Muhammad Waryah, Roohi Nigar, Amber Mahmood, Hina Shaikh, Muhammad Qasim Awan, Ikram Din Ujjan, Ali Muhammad Waryah
{"title":"Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants","authors":"Rafia Shah, Feriha Fatima Khidri, Yar Muhammad Waryah, Roohi Nigar, Amber Mahmood, Hina Shaikh, Muhammad Qasim Awan, Ikram Din Ujjan, Ali Muhammad Waryah","doi":"10.1007/s10534-023-00561-2","DOIUrl":"10.1007/s10534-023-00561-2","url":null,"abstract":"<div><p>This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between <i>LOX</i> gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while <i>LOX</i> gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (<i>p</i> < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (<i>p</i> < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, <i>LOX</i> gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30–24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"447 - 459"},"PeriodicalIF":4.1,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138574685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometalsPub Date : 2023-12-06DOI: 10.1007/s10534-023-00556-z
Nikhat Firdaus, Ishrat Altaf, Zafar Iqubal, Osama Adeel khan Sherwani, Shamiuddin khan, Mohd Kashif, Bhupendra Kumar, Mohammad Owais
{"title":"Green synthesis of silver nanoparticles employing hamdard joshanda extract: putative antimicrobial potential against gram positive and gram negative bacteria","authors":"Nikhat Firdaus, Ishrat Altaf, Zafar Iqubal, Osama Adeel khan Sherwani, Shamiuddin khan, Mohd Kashif, Bhupendra Kumar, Mohammad Owais","doi":"10.1007/s10534-023-00556-z","DOIUrl":"10.1007/s10534-023-00556-z","url":null,"abstract":"<div><p>The bio-mediated synthesis of nanoparticles offers a sustainable and eco-friendly approach. In the present study, silver nanoparticles (AgNPs) were synthesized using Joshanda extract, a commercially available herbal formulation derived from a traditional medicinal plant, as a reducing and stabilizing agent. The as-synthesized AgNPs were characterized using UV–Vis spectroscopy, dynamic light scattering (DLS), X-ray Diffraction (XRD) study, and Fourier-transform infrared (FTIR) analysis. UV–Vis spectroscopy exhibited a prominent absorption peak at 430 nm, confirming the formation of AgNPs. DLS analysis revealed the size distribution of the nanoparticles, ranging from 80 to 100 nm, and zeta potential measurements indicated a surface charge of − 14.4 mV. The XRD analysis provide evidence for the presence of a face-centered cubic structure within the silver nanoparticles. FTIR analysis further elucidated the interaction of bioactive compounds from the Joshanda extract with the AgNPs’ surface. Strong peaks at 765–829 cm<sup>−1</sup> indicated C–Cl stretching vibrations of alkyl halides, while the stretching of alkenes C=C was observed at 1641 cm<sup>−1</sup>. Moreover, the presence of alcohols and phenol (OH) groups was identified at 3448 cm<sup>−1</sup>, suggesting their involvement in nanoparticle stabilization. The antimicrobial potential of the synthesized AgNPs was evaluated against both gram-negative <i>Pseudomonas aeruginosa</i> and gram-positive <i>Streptococcus mutans</i> using zone of inhibition assays. The AgNPs exhibited remarkable inhibitory effects against both types of bacteria. Additionally, AgNPs-treated groups demonstrated a significant increase in reactive oxygen species (ROS) levels, indicating potential of as-synthesized AgNPs in disruption of the target microbial membranes. Furthermore, the as-synthesized AgNPs exhibited notable anti-biofilm properties by effectively hindering the development of mature biofilms. This study highlights the efficient green synthesis of AgNPs using Joshanda extract and also provides insights into their physico-chemical properties of as-synthesized nanoparticles. The demonstrated antimicrobial activity against both gram-negative and gram-positive bacteria, along with biofilm inhibition potential, underscores the promising applications of the as-synthesized AgNPs in the field of biomedical and environmental sciences. The study bridges traditional knowledge with contemporary nanotechnology, offering a novel avenue for the development of eco-friendly antimicrobial agents.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"389 - 403"},"PeriodicalIF":4.1,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tattoo inks: evaluation of cellular responses and analysis of some trace metals","authors":"Sumru Sozer Karadagli, Gizem Kaftan, Islam Cansever, Guliz Armagan, Ozlem Sogut","doi":"10.1007/s10534-023-00564-z","DOIUrl":"10.1007/s10534-023-00564-z","url":null,"abstract":"<div><p>After tattoo application, inks remain in the skin, mostly in the dermal layer, and manufacturers use inks that have not been adequately evaluated for safety in tattoo production. In this study, the metal contents (Cd, Hg, Pb, and Cr) of tattoo inks available in the Turkish market were determined and the relationship between cell viability and inflammatory response of the detected metal levels was investigated. Nine tattoo inks (3 colors) from 3 different brands abbreviated as E, I, and W were examined. ICP-MS was used for element analysis. The viability of human keratinocyte cells was determined by the WST-1 assay following ink exposures at various dilutions. IL-18 levels were measured in cell culture supernatant by ELISA method following ink or metal (Cd, Cr, Hg, and Pb) exposures. The concentrations of trace elements were found in inks as follows: Cd, 0.0641–1.3857; Hg, 0.0204–0.2675; Pb, 0.8527–6.5981; Cr, 0.1731–45.3962 µg mL<sup>−1</sup>. It was observed that the levels of Pb and especially Cr in the samples exceeded the limit values. Tattoo inks reduced the cell viability in a dose- and color-dependent manner. IL-18 release was significantly increased in all groups except Cr and black ink of brand I treated cells (p < 0.05). Our results show that the metal contents of tattoo inks exceed Council of Europe Resolution values in some samples and some inks induce immune system activation (IL-18 secretion) and cytotoxic effects. It is thought that these findings may contribute to the toxic/adverse effects of tattoo inks commonly used.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"495 - 505"},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138456988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometalsPub Date : 2023-11-29DOI: 10.1007/s10534-023-00558-x
Tatiana Araujo Pereira, Breno Pannia Espósito
{"title":"Can iron chelators ameliorate viral infections?","authors":"Tatiana Araujo Pereira, Breno Pannia Espósito","doi":"10.1007/s10534-023-00558-x","DOIUrl":"10.1007/s10534-023-00558-x","url":null,"abstract":"<div><p>The redox reactivity of iron is a double-edged sword for cell functions, being either essential or harmful depending on metal concentration and location. Deregulation of iron homeostasis is associated with several clinical conditions, including viral infections. Clinical studies as well as in silico, in vitro and in vivo models show direct effects of several viruses on iron levels. There is support for the strategy of iron chelation as an alternative therapy to inhibit infection and/or viral replication, on the rationale that iron is required for the synthesis of some viral proteins and genes. In addition, abnormal iron levels can affect signaling immune response. However, other studies report different effects of viral infections on iron homeostasis, depending on the class and genotype of the virus, therefore making it difficult to predict whether iron chelation would have any benefit. This review brings general aspects of the relationship between iron homeostasis and the nonspecific immune response to viral infections, along with its relevance to the progress or inhibition of the inflammatory process, in order to elucidate situations in which the use of iron chelators could be efficient as antivirals.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"289 - 304"},"PeriodicalIF":4.1,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term Cu exposure alters CYP450s activity and induces jejunum injury and apoptosis in broilers","authors":"Lei Li, Gaolong Zhong, Yuanxu Li, Tingyu Li, Yihui Huo, Feiyang Ma, Ying Li, Hui Zhang, Jiaqiang Pan, Lianmei Hu, Jianzhao Liao, Zhaoxin Tang","doi":"10.1007/s10534-023-00559-w","DOIUrl":"10.1007/s10534-023-00559-w","url":null,"abstract":"<div><p>Copper (Cu) is an essential trace element that plays a crucial role in numerous physiopathological processes related to human and animal health. In the poultry industry, Cu is used to promote growth as a feed supplement, but excessive use can lead to toxicity on animals. Cytochrome P450 enzymes (CYP450s) are a superfamily of proteins that require heme as a cofactor and are essential for the metabolism of xenobiotic compounds. The purpose of this study was to explore the influence of exposure to Cu on CYP450s activity and apoptosis in the jejunum of broilers. Hence, we first simulated the Cu exposure model by feeding chickens diets containing different amounts of Cu. In the present study, histopathological observations have revealed morphological damage to the jejunum. The expression levels of genes and proteins of intestinal barrier markers were prominently downregulated. While the mRNA expression level of the gene associated with CYP450s was significantly increased. Additionally, apoptosis-related genes and proteins (Bak1, Bax, Caspase-9, Caspase-3, and CytC) were also significantly augmented by excessive Cu, while simultaneously decreasing the expression of Bcl-2. It can be concluded that long-term Cu exposure affects CYP450s activity, disrupts intestinal barrier function, and causes apoptosis in broilers that ultimately leads to jejunum damage.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"421 - 432"},"PeriodicalIF":4.1,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}