We have previously reported that rats are resilient to the hepatotoxic and lethal combination of chlordecone (CD) and carbon tetrachloride (CCl4) during early postnatal development. The overall findings pointed to stimulated cell division and tissue repair mechanisms as the underlying cause of resistance. The objective of the current study was to investigate if the antimitotic effect of colchicine (CLC) abolishes this resiliency to CD + CCl4 by inhibiting ongoing and stimulated cell division. We used 45-day-old rats in this study because this age group exhibited partial sensitivity to CD + CCl4 in our previous studies. Male Sprague-Dawley rats were treated with a single low intraperitoneal dose of CCl4 (100 microl/kg) or corn oil after exposure to either 10 ppm CD in the diet or a normal diet (ND) for 15 days. CLC (1 mg/kg) was administered 6 or 30 hr after CCl4 to ND or CD rats, respectively. Administration of CLC resulted in increased CCl4-induced mortality from 25% to 85% in rats pretreated with CD, in contrast to 100% survival in ND rats. Liver injury was assessed by plasma alanine transaminase (ALT) and sorbitol dehydrogenase (SDH) elevations as well as by histopathology. Hepatocellular regeneration was assessed by 3H-thymidine (3H-T) incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) studies during 0-96 hr after CCl4. Administration of CLC to ND + CCl4 rats resulted in a slight delay in cell division and tissue repair, as indicated by 3H-T incorporation and PCNA, thereby leading to prolonged liver injury as revealed by elevations in plasma ALT, SDH, and histopathological lesions. In contrast, CLC administration to CD + CCl4-treated rats further delayed and diminished cell division by 80%, which led to unrestrained progression of CCl4-induced liver injury, resulting in 85% mortality. These findings underscore the importance of ongoing and toxicant-stimulated cell division and tissue repair mechanisms in hepatotoxicity, and the need for the inclusion of age factors in risk assessment of exposure to environmental and other chemicals.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533167 | PMC |
http://dx.doi.org/10.1289/ehp.98106597 | DOI Listing |
Int J Surg
January 2025
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Background: This study tested the hypothesis that extracorporeal shockwave therapy (ECSWT) effectively rescues critical limb ischemia (CLI) in mice through the upregulation of GPR120, which protects against inflammation and angiogenesis to restore blood flow in the ischemic area.
Methods And Results: Compared with the control, ECSWT-induced GPR120-mediated anti-inflammatory effects significantly suppressed the expression of inflammatory signaling biomarkers (TAK1/MAPK family/NF-κB/IL-1β/IL-6/TNF-α/MCP-1) in HUVECs, and these effects were abolished by silencing GPR120 or by the GPR120 antagonist AH7614 (all P < 0.001).
JAMA Pediatr
January 2025
Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Importance: Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to worldwide practice variation. Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity.
View Article and Find Full Text PDFInt J Gynecol Pathol
January 2025
Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Harvard Medical School.
Ovarian clear cell carcinoma (OCCC) is an endometriosis-related neoplasm, in which traditional histologic grading does not show prognostic significance. Tumor budding was associated with poorer outcomes in OCCC in previous studies. We aimed to evaluate the prognostic significance of tumor budding in OCCC in an independent cohort.
View Article and Find Full Text PDFCurr Protoc
January 2025
Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
Balanced translocation carriers experience elevated reproductive risks, including pregnancy loss and children with anomalies due to generating chromosomally unbalanced gametes. While understanding the likelihood of producing unbalanced conceptuses is critical for individuals to make reproductive decisions, risk estimates are difficult to obtain as most balanced translocations are unique. To improve reproductive risk estimates, Drs.
View Article and Find Full Text PDFThyroid
January 2025
Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Epidemiological data suggest the population distribution of thyrotropin (TSH) values is shifted toward lower values in self-identified Black non-Hispanic individuals compared with self-identified White non-Hispanic individuals. It is unknown whether genetic differences between individuals with genetic similarities to African reference populations (GSA) and those with similarities to European reference populations (GSE) contribute to these observed differences. We aimed to compare genome-wide associations with TSH and putative causal TSH-associated variants between GSA and GSE groups.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!