المؤلفون: Dukes, David A.¹, McDonough, Carrie A.² cmcdonou@andrew.cmu.edu

المصدر: Environmental Toxicology & Chemistry. Jun2024, p1. 11p. 5 Illustrations.

مصطلحات موضوعية: *FLUOROALKYL compounds, *EXCRETION, *PERFLUOROOCTANE sulfonate, *SULFONAMIDES, *FOAM

مستخلص: Perfluoroalkyl sulfonamides (FASAs) and other FASA‐based per‐ and polyfluoroalkyl substances (PFASs) can transform into recalcitrant perfluoroalkyl sulfonates in vivo. We conducted high‐resolution mass spectrometry suspect screening of urine and tissues (kidney and liver) from mice dosed with an electrochemically fluorinated aqueous film‐forming foam (AFFF) to better understand the biological fate of AFFF‐associated precursors. The B6C3F1 mice were dosed at five levels (0, 0.05, 0.5, 1, and 5 mg kg−1 day−1) based on perfluorooctane sulfonate and perfluorooctanoate content of the AFFF mixture. Dosing continued for 10 days followed by a 6‐day depuration. Total oxidizable precursor assay of the AFFF suggested significant contributions from precursors with three to six perfluorinated carbons. We identified C4 to C6 FASAs and N‐glucuronidated FASAs (FASA‐N‐glus) excreted in urine collected throughout dosing and depuration. Based on normalized relative abundance, FASA‐N‐glus accounted for up to 33% of the total excreted FASAs in mouse urine, highlighting the importance of phase II metabolic conjugation as a route of excretion. High‐resolution mass spectrometry screening of liver and kidney tissue revealed accumulation of longer‐chain (C7 and C8) FASAs not detected in urine. Chain‐length–dependent conjugation of FASAs was also observed by incubating FASAs with mouse liver S9 fractions. Shorter‐chain (C4) FASAs conjugated to a much greater extent over a 120‐min incubation than longer‐chain (C8) FASAs. Overall, this study highlights the significance of N‐glucuronidation as an excretion mechanism for short‐chain FASAs and suggests that monitoring urine for FASA‐N‐glus could contribute to a better understanding of PFAS exposure, as FASAs and their conjugates are often overlooked by traditional biomonitoring studies. Environ Toxicol Chem 2024;00:1–11. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

المؤلفون: Dąbkowski, Kamil¹ (AUTHOR) kamil.dabkowski@gumed.edu.pl, Kreft, Ewelina¹ (AUTHOR) ewelina.kreft@gumed.edu.pl, Sałaga-Zaleska, Kornelia¹ (AUTHOR) kornelia.salaga-zaleska@gumed.edu.pl, Chyła-Danił, Gabriela¹ (AUTHOR) gabriela_chyla@gumed.edu.pl, Mickiewicz, Agnieszka² (AUTHOR) agnieszka.mickiewicz@gumed.edu.pl, Gruchała, Marcin² (AUTHOR) marcin.gruchala@gumed.edu.pl, Kuchta, Agnieszka¹ (AUTHOR) agakuchta@gumed.edu.pl, Jankowski, Maciej¹ (AUTHOR) majank@gumed.edu.pl

المصدر: International Journal of Molecular Sciences. May2024, Vol. 25 Issue 10, p5498. 10p.

مصطلحات موضوعية: *EXCRETION, *BLOOD lipids, *FAMILIAL hypercholesterolemia, *KIDNEY physiology, *INTRAPERITONEAL injections, *CHOLESTERYL ester transfer protein, *LOW density lipoproteins, *ALBUMINS

مستخلص: Hypercholesterolemia-associated oxidative stress increases the formation of oxidized low-density lipoprotein (oxLDL), which can affect endothelial cell function and potentially contribute to renal dysfunction, as reflected by changes in urinary protein excretion. This study aimed to investigate the impact of exogenous oxLDL on urinary excretion of albumin and nephrin. LDL was isolated from a patient with familial hypercholesterolemia (FH) undergoing lipoprotein apheresis (LA) and was oxidized in vitro with Cu (II) ions. Biochemical markers of LDL oxidation, such as TBARS, conjugated dienes, and free ε-amino groups, were measured. Wistar rats were treated with a single intraperitoneal injection of PBS, LDL, or oxLDL (4 mg of protein/kg b.w.). Urine was collected one day before and two days after the injection. We measured blood lipid profiles, urinary protein excretion (specifically albumin and nephrin), and markers of systemic oxidative stress (8-OHdG and 8-iso-PGF2α). The results showed that injection of oxLDL increased urinary albumin excretion by approximately 28% (310 ± 27 μg/24 h vs. 396 ± 26 μg/24 h, p = 0.0003) but had no effect on nephrin excretion. Neither PBS nor LDL had any effect on urinary albumin or nephrin excretion. Additionally, oxLDL did not affect systemic oxidative stress. In conclusion, hypercholesterolemia may adversely affect renal function through oxidatively modified LDL, which interferes with the renal handling of albumin and leads to the development of albuminuria. [ABSTRACT FROM AUTHOR]

المؤلفون: KuKanich, Kate S.¹ (AUTHOR), Anderson, Elayna E.¹ (AUTHOR), Carcamo Tzic, Astrid D.² (AUTHOR), KuKanich, Butch² (AUTHOR) kukanich@ksu.edu

المصدر: Journal of Veterinary Pharmacology & Therapeutics. May2024, Vol. 47 Issue 3, p168-174. 7p.

مصطلحات موضوعية: *URINARY tract infections, *EXCRETION, *PARENTERAL solutions, *GREYHOUNDS, *URINATION, *BITTERNESS (Taste)

مستخلص: The canine urinary excretion of florfenicol was evaluated to explore its potential for treating urinary tract infections. Nine healthy male intact purpose‐bred Beagles and four healthy client‐owned dogs each received a single oral dose of florfenicol 20 mg/kg (300 mg/mL parenteral solution) with food. All voluntary urinations were collected for 12 h. Although florfenicol is reportedly bitter tasting, 7/9 Beagles and 4/4 client‐owned dogs completely ingested the florfenicol and were enrolled; salivation (n = 1) and headshaking (n = 3) were observed. The last measured urine florfenicol concentrations were variable: Beagles (0.23–3.19 mcg/mL), Pug (3.01 mcg/mL) English Setter (21.29 mcg/mL), Greyhound (32.68 mcg/mL), and Standard Poodle (13.00 mcg/mL). Urine half‐life was similar for the Beagles and the Pug, 0.75–1.39 h, whereas the half‐life was 1.70–1.82 h for the English Setter, Greyhound, and Standard Poodle. Larger breed dogs exceeded 8 mcg/mL florfenicol (wild‐type cutoff) in their urine at 12 h, whereas the Beagles and Pug had <8 mcg/mL; it is unclear if this is an individual, breed, or size difference. These data suggest oral florfenicol may need to be administered q6‐12h for canine urinary tract infections, but further data are needed (more enrolled dogs, multiple‐dose regimens) before considering clinical trials or breed‐specific differences. [ABSTRACT FROM AUTHOR]

المؤلفون: Liu, Hui¹ (AUTHOR), Wang, Sixin¹ (AUTHOR), Chen, Meixia¹ (AUTHOR), Ji, Haifeng¹ (AUTHOR) nutrition203@163.com, Zhang, Dongyan¹ (AUTHOR) Zhdy203@126.com

المصدر: Scientific Reports. 4/14/2024, Vol. 14 Issue 1, p1-13. 13p.

مصطلحات موضوعية: *LOW-protein diet, *NITROGEN excretion, *METABOLOMICS, *SWINE, *DIETARY supplements

مستخلص: This study investigated the effects of Lactobacillus-fermented low-protein diet on the growth performance, nitrogen balance, fecal microbiota, and metabolomic profiles of finishing pigs. A total of 90 finishing pigs were assigned to one of three dietary treatments including a normal protein diet (CON) as well as two experimental diets in which a low-protein diet supplemented with 0 (LP) or 1% Lactobacillus-fermented low-protein feed (FLP). In comparison with CON, the LP and FLP significantly increased average daily gain (P = 0.044), significantly decreased feed to gain ratio (P = 0.021), fecal nitrogen (P < 0.01), urine nitrogen (P < 0.01), and total nitrogen (P < 0.01), respectively. The LP group exhibited increased abundances of unclassified_f_Selenomonadaceae, Coprococcus, Faecalibacterium, and Butyricicoccus, while the abundances of Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, and Akkermansia were enriched in the FLP group. Low-protein diet-induced metabolic changes were enriched in sesquiterpenoid and triterpenoid biosynthesis and Lactobacillus-fermented low-protein feed-induced metabolic changes were enriched in phenylpropanoid biosynthesis and arginine biosynthesis. Overall, low-protein diet and Lactobacillus-fermented low-protein diet improved the growth performance and reduce nitrogen excretion, possibly via altering the fecal microbiota and metabolites in the finishing pigs. The present study provides novel ideas regarding the application of the low-protein diet and Lactobacillus-fermented low-protein diet in swine production. [ABSTRACT FROM AUTHOR]

المؤلفون: Bonsmann, Susanne¹ (AUTHOR) susanne.bonsmann@aicuris.com, McCormick, David² (AUTHOR), Pausch, Jörg³ (AUTHOR), de Vries, Michiel⁴ (AUTHOR), Sumner, Melanie¹ (AUTHOR), Birkmann, Alexander¹ (AUTHOR), Zimmermann, Holger¹ (AUTHOR), Kropeit, Dirk¹ (AUTHOR)

المصدر: Clinical Pharmacology in Drug Development. Apr2024, Vol. 13 Issue 4, p389-403. 15p.

مصطلحات موضوعية: *ACETIC acid, *EXCRETION, *ISOMERS, *METABOLISM, *RADIOACTIVITY

مستخلص: Pritelivir is a helicase‐primase inhibitor active against HSV. Two human mass balance trials (a multiple‐dose trial and a single‐dose trial) were performed to characterize the absorption, distribution, metabolism, and excretion of 100 mg oral pritelivir combined with a single microdose of 14C‐pritelivir. Blood, urine, and feces samples were collected up to 26 days postdose. The plasma half‐life of pritelivir was 63‐67 hours. Overall, 92% and 66% of the administered dose was recovered in the multiple and single dose trials, respectively. The low recovery after the single dose (66%) was most likely related to the formulation used. The major metabolic pathway was amide hydrolysis leading to amino thiazole sulfonamide (ATS) and pyridinyl phenyl acetic acid (PPA). In plasma, pritelivir, ATS, PPA, and PPA‐acyl glucuronide accounted for 40.6%, 9.4%, 5.1%, and 0.2% of total radioactivity. More than 90% of drug‐related material was eliminated 624 hours postdose. The majority was excreted in urine (75% and 77%), followed by feces (16% and 23%). The main components in urine were PPA‐acyl glucuronide (and its isomers), ATS, and its N‐demethylated isomers. Only minor metabolites were observed in feces. In conclusion, the major metabolic pathways of pritelivir have been identified with the primary excretion route being renal. [ABSTRACT FROM AUTHOR]

المؤلفون: Challita, Elio J.¹, Bhamla, M. Saad¹ saadb@chbe.gatech.edu

المصدر: Proceedings of the National Academy of Sciences of the United States of America. 3/26/2024, Vol. 121 Issue 13, p1-3. 6p.

مصطلحات موضوعية: *CICADAS, *EXCRETION, *FLUID dynamics, *DIMENSIONAL analysis, *ELEPHANTS

مستخلص: Can insects weighing mere grams challenge our current understanding of fluid dynamics in urination, jetting fluids like their larger mammalian counterparts? Current fluid urination models, predominantly formulated for mammals, suggest that jetting is confined to animals over 3 kg, owing to viscous and surface tension constraints at microscales. Our findings defy this paradigm by demonstrating that cicadas--weighing just 2 g--possess the capability for jetting fluids through remarkably small orifices. Using dimensional analysis, we introduce a unifying fluid dynamics scaling framework that accommodates a broad range of taxa, from surface-tension-dominated insects to inertia and gravity-reliant mammals. This study not only refines our understanding of fluid excretion across various species but also highlights its potential relevance in diverse fields such as ecology, evolutionary biology, and biofluid dynamics. [ABSTRACT FROM AUTHOR]

المؤلفون: Salazar‐Cubillas, Khaterine^1,2 (AUTHOR), Corea, Edgardo^3,4 (AUTHOR), Dickhoefer, Uta^1,2 (AUTHOR) dickhoefer@aninut.uni-kiel.de

المصدر: Journal of Animal Physiology & Animal Nutrition. Mar2024, Vol. 108 Issue 2, p423-438. 16p.

مصطلحات موضوعية: *NITROGEN excretion, *TROPICAL conditions, *STANDARD deviations

مصطلحات جغرافية: EL Salvador, KENYA, PERU

مستخلص: The present study aims at evaluating whether current semimechanistic models developed for temperate cattle systems can be adopted for cattle under (sub‐) tropical husbandry systems to adequately (accurately and precisely) predict total nitrogen (TN), urine nitrogen (UN), faecal nitrogen (FN) excretion and its partition into different FN fractions. Selected models were built based on the feeding recommendations for ruminants of the British (Model A), German (Model G) and French (INRA; Model I) system. Model evaluation was conducted using eight nitrogen balance studies performed in El Salvador, Kenya and Peru (n = 392 individual observations including lactating cows, heifers and steers). Concordance correlation coefficient, root mean square errors (RMSE), and mean biases were estimated to evaluate the models' adequacy in predicting nitrogen excretion. Input variables causing greatest variation in nitrogen excretion prediction were identified by a sensitivity analysis and adjusted. Model G was able to adequately (i.e., RMSE of <25% of observed mean, systematic error of <5% of the mean square error) predict TN excretion through a compensation between overestimation of UN excretion and underestimation of FN excretion. None of the models were able to adequately predict UN, FN, and different FN fractions. Model I adequately predicted FN (RMSE = 18%) when duodenal microbial crude protein flow was increased, and the intercept used to predict FN excretion was reduced from 4.30 to 3.82 g of nitrogen per kilogram of dry matter intake. These adjustments, however, were not sufficient to predict adequately UN excretion (RMSE = 38%), individual FN fractions (RMSE > 56%), and TN (RMSE = 22%) excretion, by Model I. [ABSTRACT FROM AUTHOR]

المؤلفون: Zhu, Qiufeng¹ (AUTHOR) qiufengzhizhou@163.com, Qu, Honglei¹ (AUTHOR) leihong_qu@163.com, Kang, Ruifen^1,2 (AUTHOR) ruifenkang@cau.edu.cn, Zheng, Yunduo^1,2 (AUTHOR) zhengyunduo@cau.edu.cn, Guo, Qiuying¹ (AUTHOR) guoqiuying2001@163.com, Huang, Shimeng^1,2 (AUTHOR) shimengh@cau.edu.cn, Zhao, Lihong^1,2 (AUTHOR) zhaolihongcau@cau.edu.cn, Ma, Qiugang^1,2 (AUTHOR) maqiugang@cau.edu.cn

المصدر: Toxins. Mar2024, Vol. 16 Issue 3, p128. 12p.

مصطلحات موضوعية: *LIQUID chromatography-mass spectrometry, *EXCRETION, *LACTATION, *SOWS, *LACTATION in cattle, *STATISTICAL sampling, *URINE

مستخلص: Ochratoxin A (OTA), a mycotoxin commonly found in feedstuffs, is known for its detrimental effects on the kidneys and liver, posing significant health risks to animals and humans. This study investigated the toxicokinetics, excretion patterns, and milk transmission of Ochratoxin A (OTA) in lactating sows. The sows were administered a single oral dose of 500 μg/kg BW (body weight), followed by the systematic sampling of plasma, feces, urine, and milk. Plasma samples were collected at 0, 5, 15, and 30 min, and 1, 2, 3, 6, 9, 12, 24, 48, 72, 88, 96, and 120 h post administration. Feces samples were collected at 6 h intervals for the first 12 h, then at 12 h intervals until 120 h, while urine samples were collected at 6 h intervals up to 120 h. Milk samples were collected at 0, 6, 12, 24, 36, 48, 72, 96, and 120 h. The concentration of OTA and its primary metabolite OTα were quantitatively analyzed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results revealed that the peak plasma concentrations of OTA (920.25 ± 88.46 μg/L) were observed at 9 h following administration. The terminal elimination half-life was recorded at 78.47 ± 7.68 h, with a volume of distribution of 0.16 ± 0.003 L/kg. Moreover, this study documented the excretion of OTA and OTα across a span of 120 h, revealing that feces and urine accounted for 18.70 ± 0.04% and 8.40 ± 0.002% of the total intake amounts, respectively (calculated based on substance amounts). Furthermore, this experiment detected OTA residues in the milk of lactating sows, with the milk-to-plasma (M/P) ratio initially increasing from 0.06 to 0.46 within the first 24 h following OTA ingestion. These findings offer an exhaustive temporal analysis of OTA's toxicokinetics in lactating sows, emphasizing its pervasive distribution and elimination through various bodily excreta. [ABSTRACT FROM AUTHOR]

المؤلفون: Liu, Chang¹ (AUTHOR), Zhang, Jia‐Ying¹ (AUTHOR), Wang, Yong‐Ming¹ (AUTHOR), Cheng, Xiao‐Ling¹ (AUTHOR), Qu, Li‐Yuan¹ (AUTHOR), Wang, Yan‐Li¹ (AUTHOR), Sun, Yi‐Fan¹ (AUTHOR), Wang, Yong² (AUTHOR), Du, Zhi‐Min^3,4 (AUTHOR), Wang, Wei^2,5 (AUTHOR) wangwei26960@126.com, Wang, Jin‐Hui¹ (AUTHOR) wangjinhui@hrbmu.edu.cn

المصدر: Separation Science Plus. Feb2024, Vol. 7 Issue 2, p1-10. 10p.

مصطلحات موضوعية: *EXCRETION, *CHINESE medicine, *PHARMACOKINETICS, *SALVIA miltiorrhiza

مستخلص: Salvia miltiorrhiza Bunge is a Traditional Chinese Medicine used for the treatment of diseases related to the heart and liver. Owing to the abundance of salvianolic acids and tanshinones, S. miltiorrhiza exhibits various pharmacological activities, such as stimulating blood circulation, eliminating blood stasis, relieving menorrhea and pain, and improving polydipsia. Neocryptotanshinone (NCTS) is one of the tanshinones isolated from S. miltiorrhiza and exhibits anti‐inflammatory, hypoglycemic, and preventive effects against cardiovascular diseases; however, its pharmacokinetic properties have not been reported to date. Therefore, a simple and reliable LC–MS/MS method was developed to determine absorption, distribution, and excretion of NCTS in rat physiological samples. We demonstrated that NCTS had high oral absolute bioavailability of 85.96% ± 25.32%, and it was rapidly distributed in both the heart and brain, and the fecal excretion of NCTS was the highest. This study provides a theoretical basis for further development of NCTS as a potential clinical candidate. [ABSTRACT FROM AUTHOR]

المؤلفون: Derakhshandeh-Rishehri, Seyedeh-Masomeh¹ (AUTHOR), Franco, Luciana Peixoto¹ (AUTHOR), Hua, Yifan¹ (AUTHOR), Herder, Christian^2,3,4 (AUTHOR), Kalhoff, Hermann^5,6 (AUTHOR), Frassetto, Lynda A.⁷ (AUTHOR), Wudy, Stefan A.⁸ (AUTHOR), Remer, Thomas¹ (AUTHOR) remer@uni-bonn.de

المصدر: International Journal of Molecular Sciences. Feb2024, Vol. 25 Issue 3, p1408. 11p.

مصطلحات موضوعية: *INTERLEUKIN-18, *EXCRETION, *KIDNEY physiology, *ADULTS, *ADOLESCENCE, *ACID-base imbalances

مستخلص: High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which, in humans, is also inducible by chronic metabolic acidosis. We thus examined whether habitually high P-In and endogenous acid production during childhood and adolescence may be early indicators of incipient renal inflammatory processes later in adulthood. P-In and acid–base status were longitudinally and exclusively determined by biomarker-based assessment in 277 healthy children, utilizing phosphate and net acid excretion (NAE) measurements in 24 h urine samples repeatedly collected between the ages of 3 and 17 years. Standard deviation scores (by sex and age) were calculated for anthropometric data and for the urinary biomarkers available within age range 3–17 years. Multivariable linear regression was used to analyze the relations of phosphate excretion and NAE with the adulthood outcome circulating interleukin-18 (IL-18), a marker of inflammation and kidney dysfunction. After adjusting for growth- and adulthood-related covariates and pro-inflammatory biomarkers to rule out confounding by non-renal inflammatory processes, regression models revealed a significant positive relationship of long-term NAE (p = 0.01), but not of long-term phosphate excretion with adult serum IL-18. Similar significant positive regression results were obtained after replacing NAE with 24 h urinary ammonium excretion as the exposition variable. Our results suggest that even moderate elevations in renal ammonia production, as caused by habitually higher acid loading during growth, may affect the intrarenal pro-inflammatory system in the long-term, known to be boosted by acidosis-induced raised ammoniagenesis. [ABSTRACT FROM AUTHOR]