The biological effects of lead are well defined; however, neither the risk exposure level nor the subcellular mechanism of its action is completely clear. The present work was undertaken to investigate the effects of low level and long term lead exposure on the composition and expression of rat renal gangliosides. In order to identify ganglioside expression, frozen sections of kidneys were stained with monoclonal antibodies GMB16 (GM1 specific), GM28 (GM2 specific), AMR-10 (GM4 specific) and CDW 60 (9-O-Ac-GD3 specific). Strong reactivity was observed for GMB28, AMR-10 and CDW 60, while GMB16 developed only weak labelling in treated kidney compared with the control. The alterations in the expression of renal gangliosides observed by immunohistochemistry were accompanied by quantitative and qualitative changes in the thin layer chromatography of total gangliosides isolated from kidney tissues. Lead treatment produced a significant increase in 9-O-Ac GD3, a ganglioside involved in apoptotic processes. In agreement with this result, a significant decrease in the number of apoptotic glomerular cells was observed with the TUNEL assay. These findings lead us to suggest that alterations in renal gangliosides produced by low level lead exposure are associated with the apoptotic processes that take place in the kidney. These findings provide evidence that low level and long term lead exposure produces renal ganglioside alterations with urinary microalbumin excretion. The results suggest that lead levels within the limits of biological tolerance already cause molecular renal damage without clinical signs of toxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/jat.1256 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[A study on the effects of Anti-GM1 on the differentiation and cytotoxic activity of NK cells in nude mice].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
September 2024
Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China. *Corresponding authors, E-mail:
Article Synopsis
- The study aimed to explore how Anti-ganglioside GM1 antibodies (Anti-GM1) affect the natural killer (NK) cells' ability to kill cancer cells in nude mice by altering their differentiation.
- Researchers used a detailed staining method to identify NK cell characteristics in kidney cancer tissues and immunized mice with GM1 to produce Anti-GM1.
- The results showed that Anti-GM1 significantly reduced NK cell activity, promoted their maturation, and decreased key signaling molecules (IFN-γ and GzmB) involved in their killing function compared to a control group.
Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats.
Toxicology
November 2024
Instituto de Investigación Biomédica de Salamanca (IBSAL) de la Fundación Instituto de Ciencias de la Salud de Castilla y León (ICSCYL), Salamanca, Spain; Universidad de Salamanca (USAL), Departamento de Fisiología y Farmacología, Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; National Network for Kidney Research REDINREN, RD016/0009/0025, Instituto de Salud Carlos III, Madrid, Spain; Group of Biomedical Research on Critical Care (BioCritic), Valladolid, Spain. Electronic address:
Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury.
View Article and Find Full Text PDFNormal and Dysregulated Sphingolipid Metabolism: Contributions to Podocyte Injury and Beyond.
Cells
May 2024
Peggy and Harold Katz Family Drug Discovery Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Podocyte health is vital for maintaining proper glomerular filtration in the kidney. Interdigitating foot processes from podocytes form slit diaphragms which regulate the filtration of molecules through size and charge selectivity. The abundance of lipid rafts, which are ordered membrane domains rich in cholesterol and sphingolipids, near the slit diaphragm highlights the importance of lipid metabolism in podocyte health.
View Article and Find Full Text PDFAutomated Machine Learning and Explainable AI (AutoML-XAI) for Metabolomics: Improving Cancer Diagnostics.
J Am Soc Mass Spectrom
June 2024
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
Metabolomics generates complex data necessitating advanced computational methods for generating biological insight. While machine learning (ML) is promising, the challenges of selecting the best algorithms and tuning hyperparameters, particularly for nonexperts, remain. Automated machine learning (AutoML) can streamline this process; however, the issue of interpretability could persist.
View Article and Find Full Text PDFFirst-in-human single-dose study of nizubaglustat, a dual inhibitor of ceramide glucosyltransferase and non-lysosomal glucosylceramidase: Safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending and multiple doses in healthy adults.
Mol Genet Metab
January 2024
Azafaros AG, Dufourstrasse 25, 4052 Basel, Switzerland.
Nizubaglustat is a novel, orally available, brain penetrant, potent, and selective dual inhibitor of ceramide glucosyltranferase and non-lysosomal neutral glucosylceramidase (NLGase), which is currently under development for the treatment of subjects with neurological manifestations in primary and secondary gangliosidoses. The objectives of this first-in-human study were to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics (PD) of single oral doses of nizubaglustat after single (1, 3, and 9 mg) and multiple oral doses (9 mg once per day (QD) over 14 days) in healthy adults. Nizubaglustat was rapidly absorbed and systemic exposure was dose-proportional.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!