Carcinogenicity and chronic toxicity of 2,4-dichloro-1-nitrobenzene (2,4-DCNB) were examined by dietary administration to F344/DuCrj rats and Crj:BDF(1) mice of both sexes for 2 years. Dietary administration commenced when the animals were 6 weeks old. The dietary concentration of 2,4-DCNB was 0 (control), 750, 1,500 and 3,000 ppm (w/w) for male and female rats; 0, 750, 1,500 and 3,000 ppm for male mice; and 0, 1,500, 3,000 and 6,000 ppm for female mice. In rats, there was a dose-dependent and significant induction of renal cell adenomas and carcinomas in both sexes and of preputial glands adenomas in males. In all the 2,4-DCNB-fed groups of both sexes, the incidence of atypical tubular hyperplasia, a pre-neoplastic lesion in the kidney, in the proximal tubule was significantly increased. In mice, there was a dose-dependent and significant induction of hepatocellular adenomas, hepatocellular carcinomas, hepatoblastomas and peritoneal hemangiosarcomas in both sexes. The incidence of acidophilic hepatocellular foci was also significantly increased in female mice. Thus, clear evidence of carcinogenic activity of 2,4-DCNB by 2-year feeding was demonstrated in both rats and mice.
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http://dx.doi.org/10.1007/s00204-012-0890-7 | DOI Listing |
Acta Pharm Sin B
December 2024
State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361102, China.
The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands.
View Article and Find Full Text PDFPeerJ
January 2025
University of Amsterdam, Amsterdam, Netherlands.
Background: Achilles tendinopathy (AT) management can be difficult, given the paucity of effective treatment options and the degenerative nature of the condition. Innovative therapies for Achilles tendinopathy are therefore direly needed. New therapeutic developments predominantly begin with preclinical animal and in vitro studies to understand the effects at the molecular level and to evaluate toxicity.
View Article and Find Full Text PDFChem Pharm Bull (Tokyo)
January 2025
Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
Osteoporosis is caused by an imbalance between bone resorption and formation, which decreases bone mass and strength and increases the risk of fracture. Therefore, osteoporosis is treated with oral resorption inhibitors, such as bisphosphonates, and parenteral osteogenic drugs, including parathyroid hormone and antisclerostin antibodies. However, orally active osteogenic drugs have not yet been developed.
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January 2025
Faculty of Pharmacy, Iryo Sosei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan.
Atopic dermatitis (AD), also known as eczema, is a chronic or relapsing inflammatory skin disease characterized by repeated exacerbations and remissions. Here, we investigated the effects of squid phospholipids (PLs) extracted from Todarodes pacificus on AD. The composition of squid PLs was analyzed using thin-layer chromatography and high-performance liquid chromatography, and the effects of PLs on AD were investigated using a rat paw edema model and an AD-like mouse model (NC/Nga mice).
View Article and Find Full Text PDFCardiovasc Res
January 2025
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Aims: The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health.
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