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1.
Drugs ; 82(10): 1077-1094, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35779234

RESUMO

The primary hyperoxalurias are three rare inborn errors of the glyoxylate metabolism in the liver, which lead to massively increased endogenous oxalate production, thus elevating urinary oxalate excretion and, based on that, recurrent urolithiasis and/or progressive nephrocalcinosis. Frequently, especially in type 1 primary hyperoxaluria, early end-stage renal failure occurs. Treatment possibilities are scare, namely, hyperhydration and alkaline citrate medication. In type 1 primary hyperoxaluria, vitamin B6, though, is helpful in patients with specific missense or mistargeting mutations. In those vitamin B6 responsive, urinary oxalate excretion and concomitantly urinary glycolate is significantly decreased, or even normalized. In patients non-responsive to vitamin B6, RNA interference medication is now available. Lumasiran® is already available on prescription and targets the messenger RNA of glycolate oxidase, thus blocking the conversion of glycolate into glyoxylate, hence decreasing oxalate, but increasing glycolate production. Nedosiran blocks liver-specific lactate dehydrogenase A and thus the final step of oxalate production. Similar to vitamin B6 treatment, where both RNA interference urinary oxalate excretion can be (near) normalized and plasma oxalate decreases, however, urinary and plasma glycolate increases with lumasiran treatment. Future treatment possibilities are on the horizon, for example, substrate reduction therapy with small molecules or gene editing, induced pluripotent stem cell-derived autologous hepatocyte-like cell transplantation, or gene therapy with newly developed vector technologies. This review provides an overview of current and especially new and future treatment options.


Assuntos
Hiperoxalúria Primária , Glicolatos , Glioxilatos , Humanos , Hiperoxalúria Primária/tratamento farmacológico , Oxalatos/metabolismo , RNA Interferente Pequeno , Vitaminas
2.
Physiol Rep ; 10(14): e15357, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35851836

RESUMO

Ob/ob mice have recently emerged as a model for obesity-related hyperoxaluria as they are obese and excrete more urine oxalate compared to wild type mice. Ob/ob mice are deficient of leptin and develop obesity with hyperphagia and hyperinsulinemia. We hypothesized that insulin resistance and the gut microbiome contribute to hyperoxaluria in ob/ob mice. We developed a new liquid chromatography-mass spectrometry assay for urine oxalate and first compared urine oxalate excretion in ob/ob mice before and after ablation of intestinal bacteria with a standard antibiotic cocktail. We then compared urine oxalate excretion in ob/ob mice before and after leptin replacement or pioglitazone treatment, two maneuvers that reduce insulin resistance in ob/ob mice. Ob/ob mice excreted more oxalate into the urine in a 24-h period compared to wild type mice, but antibiotic, leptin, or pioglitazone treatment did not change urine oxalate excretion in ob/ob mice. Unexpectedly, we found that when food intake was carefully matched between ob/ob and wild type mice, the amount of 24-h urine oxalate excretion did not differ between the two mouse strains, suggesting that ob/ob mice excrete more urine oxalate because of hyperphagia. Since the level of urine oxalate excretion in wild type mice in our study was higher than those reported in prior studies, future work will be needed to standardize the measurement of urine oxalate and to define the range of urine oxalate excretion in wild type mice so that accurate and valid comparisons can be made between wild type mice and ob/ob mice or other mouse models.


Assuntos
Microbioma Gastrointestinal , Hiperoxalúria , Resistência à Insulina , Oxalatos , Animais , Antibacterianos/farmacologia , Hiperoxalúria/etiologia , Hiperoxalúria/urina , Hiperfagia/urina , Leptina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Obesos , Obesidade/microbiologia , Obesidade/urina , Oxalatos/urina , Pioglitazona/farmacologia
3.
BMJ Case Rep ; 15(7)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787489

RESUMO

A kidney transplant recipient with a medical history of type 1 diabetes mellitus (T1DM) presents to the clinic with an acute kidney injury (AKI) and diarrhoea. Kidney biopsy found deposition of focal oxalate crystals, and further investigation revealed a raised 24-hour urinary oxalate and reduced faecal elastase. Therefore, we present a case of acute oxalate nephropathy (AON) secondary to enteric hyperoxaluria as a result of pancreatic insufficiency caused by T1DM. T1DM is a common cause of end-stage renal failure and exocrine pancreatic insufficiency. Therefore, AON secondary to enteric hyperoxaluria should be considered in patients with a transplant AKI. Earlier testing of 24-hour urinary oxalate and faecal elastase could generate diagnosis before biopsy results and allow commencement of pancreatic replacement therapy earlier to avoid permanent loss of kidney function.


Assuntos
Injúria Renal Aguda , Diabetes Mellitus Tipo 1 , Insuficiência Pancreática Exócrina , Hiperoxalúria , Injúria Renal Aguda/complicações , Diabetes Mellitus Tipo 1/complicações , Insuficiência Pancreática Exócrina/complicações , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/diagnóstico , Rim , Oxalatos/urina , Elastase Pancreática
4.
Oncogene ; 41(29): 3719-3731, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35739335

RESUMO

Metabolic reprogramming has been shown to be involved in cancer-induced pre-metastatic niche (PMN) formation, but the underlying mechanisms have been insufficiently explored. Here, we showed that hydroxyacid oxidase 1 (HAO1), a rate-limiting enzyme of oxalate synthesis, was upregulated in the alveolar epithelial cells of mice bearing metastatic breast cancer cells at the pre-metastatic stage, leading to oxalate accumulation in lung tissue. Lung oxalate accumulation induced neutrophil extracellular trap (NET) formation by activating NADPH oxidase, which facilitated the formation of pre-metastatic niche. In addition, lung oxalate accumulation promoted the proliferation of metastatic cancer cells by activating the MAPK signaling pathway. Pharmacologic inhibition of HAO1 could effectively suppress the lung oxalate accumulation induced by primary cancer, consequently dampening lung metastasis of breast cancer. Breast cancer cells induced HAO1 expression and oxalate accumulation in alveolar epithelial cells by activating TLR3-IRF3 signaling. Collectively, these findings underscore the role of HAO1-mediated oxalate metabolism in cancer-induced lung PMN formation and metastasis. HAO1 could be an appealing therapeutic target for preventing lung metastasis of cancer.


Assuntos
Armadilhas Extracelulares , Neoplasias Pulmonares , Oxirredutases do Álcool , Animais , Pulmão/patologia , Neoplasias Pulmonares/patologia , Camundongos , Oxalatos
5.
Arch Biochem Biophys ; 727: 109325, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35749806

RESUMO

BACKGROUND: The ossification of renal tubular epithelial cells (RTECs) plays an important initial role in the formation of kidney stones, but its specific mechanism is still unclear. The JAK2/STAT3 signaling pathway is important for bone cell differentiation. Accordingly, we explored the role and mechanism of the JAK2/STAT3 signaling pathway in the ossification of RTECs. METHODS: We used oxalate or ethylene glycol to construct kidney stone models in vitro and in vivo, and investigated the expression of osteogenic-specific genes, osteogenesis ability, and JAK2/STAT3 signaling in the kidney stone models by western blotting, qRT-PCR, immunofluorescence, and immunohistochemistry. Then, genetic engineering or drugs were used to inhibit the expression or activation of JAK2, and the expression of osteogenic-specific genes and the osteogenic ability of the RTECs were determined again. RESULTS: In the in vitro and in vivo kidney stone models, the expression of osteogenic specific genes in the RTECs was significantly upregulated, the osteogenic capacity was significantly increased, and the expression of p-JAK2 (phospho-JAK2) and p-STAT3 (phospho-STAT3) was significantly increased. When the expression or activation of JAK2 was inhibited, the ossification of RTECs and the formation of kidney stones was reversed. CONCLUSIONS: During the formation of kidney stones, RTECs undergo obvious ossification, and the JAK2/STAT3 signaling pathway plays a key positive regulatory role in this process.


Assuntos
Cálculos Renais , Osteogênese , Diferenciação Celular , Humanos , Janus Quinase 2/metabolismo , Oxalatos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
6.
Carbohydr Polym ; 291: 119599, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35698346

RESUMO

Fibre bundles are groups of elementary fibres glued together thanks to the middle lamella, and are the main fraction in plant fibre composites. In this study, relationship between the mechanical properties of flax fibre bundles, chemical composition and cellulose structure were investigated. To do so, a sequential biopolymer extraction was implemented. Fibre bundles were first depectinated by oxalate extraction, and then the hemicelluloses were extracted by LiCl/dimethyl sulfoxide (DMSO) and KOH. The oxalate extract consisted of homogalacturonans and type I rhamnogalacturonans, while the LiCl extract was composed mainly of glucomannans and the KOH extract of xyloglucans. The KOH stage resulted in the appearance of cellulose II in flax bundles. The extraction of pectin and hemicelluloses led to the disappearance of the middle lamella concomitant with a decrease in the tensile Young's modulus and maximum strength. Finally, the fibre bundle composition, ultrastructure and mechanical properties are discussed together in view of the thin middle lamella.


Assuntos
Linho , Parede Celular/química , Celulose/química , Oxalatos , Polímeros/metabolismo
7.
Mol Med Rep ; 26(2)2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35703358

RESUMO

The present study aimed to evaluate the role and mechanism of ferrostatin­1 (Fer­1) in oxalate (Ox)­induced renal tubular epithelial cell injury, fibrosis, and calcium oxalate (CaOx) stone formation. A CaOx model in mice kidneys was established via intraperitoneal injection of 80 mg/kg glyoxylic acid for 14 days. The mice were randomly divided into three groups (n=6), namely, the control (Con), the CaOx group, and the CaOx + Fer­1 group. Cultured human renal tubular epithelial cells (HK­2 cells) were randomly divided into three groups (n=3), namely, the control (Con), the Ox group, and the Ox + Fer­1 group. The levels of heme oxygenase 1 (HO­1), superoxide dismutase 2 (SOD2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) were assessed by immunofluorescence and western blot analysis. Renal tubular injury and apoptosis were evaluated by H&E and TUNEL staining. Kidney interstitial fibrosis was evaluated by Masson and Sirius red staining, and the levels of E­cadherin, vimentin and α­SMA were detected by immunofluorescence or western blot analysis. Mitochondrial structure was observed using a transmission electron microscope. The levels of reactive oxygen species (ROS) were determined by flow cytometry and CaOx stone formation was evaluated by von Kossa staining. The results revealed that in comparison with the Con group, mitochondrial injury under glyoxylic acid treatment was observed by TEM. The expression of GPX4 and SLC7A11 in the CaOx and Ox groups was downregulated (P<0.05), whereas the expression of HO­1 and SOD2 was upregulated (P<0.05). Renal tissue damage, apoptosis of renal tubular epithelial cells, and interstitial fibrosis were increased in the CaOx and Ox groups (P<0.05). In comparison with the CaOx or Ox group, the expression of GPX4 and SLC7A11 in the CaOx + Fer­1 or Ox + Fer­1 group was upregulated (P<0.05), whereas that of HO­1 and SOD2 was downregulated (P<0.05). Renal tissue damage, apoptosis of renal tubular epithelial cells and interstitial fibrosis were decreased following Fer­1 treatment (P<0.05). The ROS level was also decreased following Fer­1 treatment. Moreover, CaOx stone formation was decreased in the CaOx + Fer­1 group (P<0.05). In conclusion, Fer­1 alleviated Ox­induced renal tubular epithelial cell injury, fibrosis, and CaOx stone formation by inhibiting ferroptosis.


Assuntos
Oxalato de Cálcio , Ferroptose , Animais , Oxalato de Cálcio/química , Oxalato de Cálcio/metabolismo , Oxalato de Cálcio/farmacologia , Cicloexilaminas , Células Epiteliais/metabolismo , Fibrose , Rim/patologia , Camundongos , Oxalatos/metabolismo , Fenilenodiaminas , Espécies Reativas de Oxigênio/metabolismo
8.
Org Lett ; 24(24): 4415-4420, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35686936

RESUMO

C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.


Assuntos
Monoterpenos Acíclicos , Receptores Odorantes , Monoterpenos Acíclicos/química , Ésteres/química , Humanos , Ligação de Hidrogênio , Oxalatos , Receptores Odorantes/agonistas
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(5): 583-587, 2022 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35753728

RESUMO

We reported a case of oxalate crystal-related acute kidney injury caused by orlistat. The patient was admitted for nephrotic syndrome and acute kidney injury. The pathomorphological assessment of renal biopsy showed intratubular oxalate crystals. The patient reported that she had taken orlistat regularly to loss weight for more than a year. This patient had a habit of drinking vegetable soup and strong herbal tea daily. Orlistat, an intestinal lipase inhibitor, may cause secondary hyperoxaluria, that is, intestinal hyperoxaluria. Dietary habits could be a common precipitating factor for orlistat-relevant hyperoxaluria. It was comprehensively considered to be oxalate crystal-related acute renal injury, and the patient's renal function recovered gradually after drug withdrawal. Clinicians should pay attention to screening drug-related acute kidney injury including orlistat when observing patients with unexplained acute kidney injury, and renal biopsy should be performed if necessary. It is also important to warn people who take the orlistat for weight loss about the side effects of this drug so as to adjust the eating habits.


Assuntos
Injúria Renal Aguda , Hiperoxalúria , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/complicações , Feminino , Humanos , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/complicações , Hiperoxalúria/diagnóstico , Orlistate/efeitos adversos , Oxalatos , Verduras
11.
Plant Signal Behav ; 17(1): 2062555, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35510715

RESUMO

The ability to biosynthesize oxalic acid can provide beneficial functions to plants; however, uncontrolled or prolonged exposure to this strong organic acid results in multiple physiological problems. Such problems include a disruption of membrane integrity, mitochondrial function, metal chelation, and free radical formation. Recent work suggests that a CoA-dependent pathway of oxalate catabolism plays a critical role in regulating tissue oxalate concentrations in plants. Although this CoA-dependent pathway of oxalate catabolism is important, large gaps in our knowledge of the enzymes catalyzing each step remain. Evidence that an oxalyl-CoA decarboxylase (OXC) catalyzes the second step in this pathway, accelerating the conversion of oxalyl-CoA to formyl-CoA, has been reported. Induction studies revealed that OXC gene expression was upregulated in response to an exogenous oxalate supply. Phylogenetic analysis indicates that OXCs are conserved across plant species. Evolutionarily the plant OXCs can be separated into dicot and monocot classes. Multiple sequence alignments and molecular modeling suggest that OXCs have similar functionality with three conserved domains, the N-terminal PYR domain, the middle R domain, and the C-terminal PP domain. Further study of this CoA-dependent pathway of oxalate degradation would benefit efforts to develop new strategies to improve the nutrition quality of crops.


Assuntos
Carboxiliases , Acil Coenzima A , Carboxiliases/genética , Carboxiliases/metabolismo , Modelos Moleculares , Oxalatos/metabolismo , Ácido Oxálico , Filogenia
12.
J Org Chem ; 87(12): 8237-8247, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35612278

RESUMO

Construction of challenging and important all-carbon quaternary centers has received growing attention. Herein, with oxalates as activating groups for tertiary alcohols, we report photoredox-catalyzed gem-difluoroallylation to construct all-carbon quaternary centers enabled by efficient tertiary radical addition to α-trifluoromethyl alkenes. This transformation shows good functional group tolerance for both α-trifluoromethyl alkenes and oxalates. Moreover, this strategy is also successfully applied to the synthesis of monofluoralkenes from the corresponding electron-rich gem-difluoroalkenes and cesium tertiary alkyl oxalates under modified conditions.


Assuntos
Carbono , Oxalatos , Álcoois , Alcenos , Catálise
13.
JCI Insight ; 7(13)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35608921

RESUMO

Nephrolithiasis is a common and recurrent disease affecting 9% of the US population. Hyperoxaluria is major risk factor for calcium oxalate kidney stones, which constitute two-thirds of all kidney stones. SLC26A3 (DRA, downregulated in adenoma) is an anion exchanger of chloride, bicarbonate, and oxalate thought to facilitate intestinal oxalate absorption, as evidenced by approximately 70% reduced urine oxalate excretion in knockout mice. We previously identified a small-molecule SLC26A3 inhibitor (DRAinh-A270) that selectively inhibited SLC26A3-mediated chloride/bicarbonate exchange (IC50 ~ 35 nM) and, as found here, oxalate/chloride exchange (IC50 ~ 60 nM). In colonic closed loops in mice, luminal DRAinh-A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRAinh-A270 largely prevented the 2.5-fold increase in urine oxalate/creatinine ratio. In a mouse model of oxalate nephropathy produced by a high-oxalate low-calcium diet, vehicle-treated mice developed marked hyperoxaluria with elevated serum creatinine, renal calcium oxalate crystal deposition, and renal injury, which were largely prevented by DRAinh-A270 (10 mg/kg twice daily). DRAinh-A270 administered over 7 days to healthy mice did not show significant toxicity. Our findings support a major role of SLC26A3 in intestinal oxalate absorption and suggest the therapeutic utility of SLC26A3 inhibition for treatment of hyperoxaluria and prevention of calcium oxalate nephrolithiasis.


Assuntos
Hiperoxalúria , Cálculos Renais , Animais , Antiporters , Bicarbonatos , Oxalato de Cálcio , Cloretos/metabolismo , Hiperoxalúria/tratamento farmacológico , Hiperoxalúria/etiologia , Cálculos Renais/complicações , Cálculos Renais/tratamento farmacológico , Cálculos Renais/prevenção & controle , Camundongos , Oxalatos , Transportadores de Sulfato
15.
J Virol Methods ; 306: 114554, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35623490

RESUMO

The iron flocculation method, which comprises the Fe-virus flocculate formation-filtration-resuspension steps, is extensively used to concentrate and precipitate viruses distributed in water. To apply this method to concentrate white spot syndrome virus (WSSV) in seawater, viral genomic and infective recovery yields were compared between polyethylene sulfone (PES) and polycarbonate (PC) membrane filters and two types of resuspension buffers (oxalate and ascorbate). Viral genome quantitation was determined above a 95 % limit of detection (11.48 viral DNA copies/µL) using quantitative real-time PCR. From WSSV-spiked seawater (100-106 viral DNA copies/mL), the viral genomic recovery yields of the PES-Oxalate, PC-Oxalate, PES-Ascorbate, and PC-Ascorbate conditions were 78.67 % ± 12.90 %, 84.53 % ± 24.30 %, 85.59 % ± 16.98 %, and 93.74 % ± 7.44 %, respectively. The detectable Fe-virus flocculates collected by the PC membrane were approximately 101 WSSV DNA copies/mL of seawater, a value more than 10-fold higher than that compared to the PES membrane filter (102 WSSV DNA copies/mL), regardless of the resuspension buffer types. WSSV resuspended with oxalate buffer caused mass mortality among whiteleg shrimp (Litopenaeus vannamei), inducing the expression of the virus envelope protein, VP28, similar to that of a native virus, suggesting stable viral activity during the resuspension process. Based on the PES-Ascorbate, WSSV particles could be successfully concentrated in seawater from shrimp farms with white spot disease outbreaks (approximately 102 WSSV DNA copies/mL). Collectively, these findings indicate that the simple and efficient method of iron flocculation is sufficient to concentrate WSSV in seawater and could be used as a non-invasive approach and one of the reasonable diagnostic processes for white spot disease surveillance.


Assuntos
Penaeidae , Vírus da Síndrome da Mancha Branca 1 , Animais , DNA Viral , Floculação , Ferro , Oxalatos , Água do Mar , Vírus da Síndrome da Mancha Branca 1/genética
16.
Toxicol In Vitro ; 82: 105373, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35500753

RESUMO

Estrogen therapy has used to prevent bone loss in postmenopausal women. Although therapeutically enhanced estrogen levels have been suggested, patients are exposed to greater risks of nephrolithiasis and cancer. It has been known that oxalate or bicarbonate transporter SLC26A6 is involved in oxalate homeostasis and its deletion results in kidney stone formation and addressed that patients with kidney stones possess higher cancer risk. Thus, the mechanism of the interaction between estrogen and SLC26A6 and the effect of SLC26A6 on cancer cells should be elucidated. In this study, we investigated whether ß-estradiol treatment modulates SLC26A6 expression and its bicarbonate or oxalate transporting activity and affects the proliferative and migratory ability of A549 cells. The ß-estradiol stimulation attenuated oxalate or bicarbonate transporting activities through SLC26A6. Knockdown of SLC26A6 reduced transporter activity whereas enhanced cellular migration. ß-estradiol-mediated cellular migration was independent of SLC26A6 transporter activity, whereas enhanced SLC26A6 expression attenuated cellular migration even in the presence of ß-estradiol treatment. These results indicate ß-estradiol treatment enhances cancer cell migration and dysregulates oxalate transport by inhibiting SLC26A6 activity, suggesting reduced oxalate transporting activity may involve in the oxalate homeostasis.


Assuntos
Antiporters , Neoplasias Pulmonares , Antiporters/metabolismo , Bicarbonatos/metabolismo , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Oxalatos/metabolismo , Oxalatos/farmacologia , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo
17.
Biochim Biophys Acta Mol Basis Dis ; 1868(9): 166442, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35562038

RESUMO

Meals rich in oxalate are associated with calcium oxalate (CaOx) kidney stone disease. Hydroxy-L-proline (HLP) is an oxalate precursor found in milk and collagen-containing foods. HLP has been shown to induce CaOx crystal formation in rodents. The purpose of this study was to evaluate the effect of HLP induced oxalate levels on inflammation and renal leukocytes during crystal formation. Male Sprague-Dawley rats (6-8 weeks old) were fed a control diet containing no oxalate for 3 days before being randomized to continue the control diet or 5% HLP for up to 28 days. Blood, 24 h urine, and kidneys were collected on Days 0, 7, 14, or 28. Urinary oxalate levels, crystal deposition, and renal macrophage markers were evaluated using ion chromatography-mass spectrometry, immunohistochemistry, and qRT-PCR. Renal leukocytes were assessed using flow cytometry and RNA-sequencing. HLP feeding increased urinary oxalate levels and renal crystal formation in animals within 7 days. HLP also increased renal macrophage populations on Days 14 and 28. Transcriptome analysis revealed that renal macrophages from animals fed HLP for 7 days were involved in inflammatory response and disease, stress response to LPS, oxidative stress, and immune cell trafficking. Renal macrophages isolated on Day 14 were involved in cell-mediated immunological pathways, ion homeostasis, and inflammatory response. Collectively, these findings suggest that HLP-mediated oxalate levels induce markers of inflammation, leukocyte populations, and reprograms signaling pathways in macrophages in a time-dependent manner. Additional studies investigating the significance of oxalate on renal macrophages could aid in our understanding of kidney stone formation.


Assuntos
Oxalato de Cálcio , Cálculos Renais , Animais , Oxalato de Cálcio/química , Oxalato de Cálcio/metabolismo , Hidroxiprolina , Inflamação , Cálculos Renais/metabolismo , Macrófagos/metabolismo , Masculino , Nefrolitíase , Oxalatos , Ratos , Ratos Sprague-Dawley
18.
Eur J Med Chem ; 237: 114396, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35500475

RESUMO

The synthesis and biological evaluation of double glycolate oxidase/lactate dehydrogenase inhibitors containing a salicylic acid moiety is described. The target compounds are obtained in an easily scalable two-step synthetic procedure. These compounds showed low micromolar IC50 values against the two key enzymes in the metabolism of glyoxylate. Mechanistically they behave as noncompetitive inhibitors against both enzymes and this fact is supported by docking studies. The biological evaluation also includes in vitro and in vivo assays in hyperoxaluric mice. The compounds are active against the three types of primary hyperoxalurias. Also, possible causes of adverse effects, such as cyclooxygenase inhibition or renal toxicity, have been studied and discarded. Altogether, this makes this chemotype with drug-like structure a good candidate for the treatment of primary hyperoxalurias.


Assuntos
Hiperoxalúria Primária , Oxalatos , Oxirredutases do Álcool , Animais , Hiperoxalúria Primária/metabolismo , Hiperoxalúria Primária/terapia , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Camundongos , Oxalatos/metabolismo , Ácido Salicílico/farmacologia
19.
Anal Methods ; 14(19): 1897-1903, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35506748

RESUMO

In this paper, a peroxyoxalate chemiluminescence (CL) recovery system based on the interaction of N-doped graphene oxide nanosheets (N-GONs) and an oligopeptide for copper(II) ion detection has been reported. N-GONs as an excellent CL enhancer are prepared by the hydrothermal method using citric acid and ammonia, and the morphology and structure are characterized in detail by TEM, XPS, FT-IR and UV/vis, etc. In the bis(2,4,6-trichlorophenyl)oxalate (TCPO) and hydrogen peroxide (TCPO + H2O2) CL reaction system, the addition of N-GONs gives a remarkable CL emission, which can be quenched by an oligopeptide composed of ten amino acid residues due to the interaction between the N-GON plane and the oligopeptide strand. While in the presence of copper(II) ion, the quenched CL is recovered gradually along with the addition of copper(II) ion in the system. Based on the above CL reactions, a TCPO + H2O2 + N-GONs + oligopeptide CL system is constructed, achieving an ultra-sensitive and selective detection of copper(II) ion in environmental water samples. The detection limit of this method is as low as 0.2 pmol L-1, which is at least three orders of magnitude lower than other CL methods. The N-GONs and oligopeptide involved in the CL system are environmentally friendly, making it possess potential in the detection of copper(II) ion in environmental water samples.


Assuntos
Cobre , Luminescência , Grafite , Peróxido de Hidrogênio/química , Medições Luminescentes/métodos , Oligopeptídeos , Oxalatos , Espectroscopia de Infravermelho com Transformada de Fourier , Água
20.
Artigo em Inglês | MEDLINE | ID: mdl-35457378

RESUMO

In rhizospheric soil, arsenic can be activated by both biological and abiotic reactions with plant exudates or phosphates, but little is known about the relative contributions of these two pathways. The effects of microorganisms, low-molecular-weight organic acid salts (LMWOASs), and phosphates on the migration of As in unrestored and nano zero-valent iron (nZVI)-restored soil were studied in batch experiments. The results show that As released by microbial action accounted for 17.73%, 7.04%, 92.40%, 92.55%, and 96.68% of the total As released in unrestored soil with citrate, phytate, malate, lactate, and acetate, respectively. It was only suppressed in unrestored soil with oxalate. In restored soil, As was still released in the presence of oxalate, citrate, and phytate, but the magnitude of As release was inhibited by microorganisms. The application of excess nZVI can completely inhibited As release processes induced by phosphate in the presence of microorganisms. Microbial iron reduction is a possible mechanism of arsenic release induced by microorganisms. Microorganisms and most environmental factors promoted As release in unrestored soil, but the phenomenon was suppressed in restored soil. This study helps to provide an effective strategy for reducing the secondary release of As from soils due to replanting after restoration.


Assuntos
Arsênio , Recuperação e Remediação Ambiental , Poluentes do Solo , Arsênio/análise , Ácido Cítrico , Ferro/análise , Oxalatos , Fosfatos , Ácido Fítico , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
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