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1.
Int J Mol Sci ; 23(10)2022 May 20.
Article in English | MEDLINE | ID: mdl-35628567

ABSTRACT

Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) are implicated in inflammatory reactions and vascular complications in diabetes. Signaling pathways downstream of RAGE are involved in NF-κB activation. In this study, we examined whether ethanol extracts of Saururus chinensis (Lour.) Baill. (SE) could affect RAGE signaling and vascular relaxation in streptozotocin (STZ)-induced diabetic rats. Treatment with SE inhibited AGEs-modified bovine serum albumin (AGEs-BSA)-elicited activation of NF-κB and could compete with AGEs-BSA binding to RAGE in a dose-dependent manner. Tumor necrosis factor-α (TNF-α) secretion induced by lipopolysaccharide (LPS)-a RAGE ligand-was also reduced by SE treatment in wild-type Ager+/+ mice as well as in cultured peritoneal macrophages from Ager+/+ mice but not in Ager-/- mice. SE administration significantly ameliorated diabetes-related dysregulation of acetylcholine-mediated vascular relaxation in STZ-induced diabetic rats. These results suggest that SE would inhibit RAGE signaling and would be useful for the improvement of vascular endothelial dysfunction in diabetes.


Subject(s)
Diabetes Mellitus, Experimental , Saururaceae , Animals , Carrier Proteins , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Inflammation/drug therapy , Mice , NF-kappa B/metabolism , Plant Extracts/pharmacology , Rats , Receptor for Advanced Glycation End Products/genetics , Receptor for Advanced Glycation End Products/metabolism , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Saururaceae/metabolism , Vasodilation
2.
J Toxicol Sci ; 34 Suppl 1: SP147-55, 2009.
Article in English | MEDLINE | ID: mdl-19265281

ABSTRACT

To investigate the optimal administration period for evaluating ovarian toxicity that reflects abnormal female fertility in the repeated dose toxicity study, atrazine, a potent herbicide with endocrine-disrupting activity, was administered to female Sprague-Dawley (Slc:SD) rats for two or four weeks at doses of 3, 30 or 300 mg/kg for the repeated dose toxicity study, and at doses of 3, 30 or 100 mg/kg for the female fertility study from two weeks before mating to Day 7 of gestation. In the two-week repeated dose toxicity study, prolongation of diestrus and histopathological findings such as loss of the currently formed corpora lutea, decrease in the numbers of previously formed corpora lutea, increase in large-sized atretic follicles, and swelling of the previously formed luteal cells were observed in the 300 mg/kg group, suggesting that atrazine had an anovulatory effect through suppression of the luteinizing hormone surge. In the female fertility study, copulation failure caused by prolongation of diestrus was observed in one animal in the 100 mg/kg group, which could be due to the anovulatory effect of atrazine. It is demonstrated that the effect of atrazine on female fertility can be assessed by detailed histopathological examination of ovaries in a two-week repeated dose toxicity study, provided the appropriate dose levels are selected.


Subject(s)
Atrazine/toxicity , Fertility/drug effects , Herbicides/toxicity , Ovary/drug effects , Toxicity Tests/methods , Animals , Atrazine/administration & dosage , Body Weight/drug effects , Copulation/drug effects , Corpus Luteum/drug effects , Corpus Luteum/metabolism , Corpus Luteum/pathology , Drug Administration Schedule , Estrous Cycle/drug effects , Female , Herbicides/administration & dosage , Japan , Male , Organ Size/drug effects , Ovarian Follicle/drug effects , Ovarian Follicle/metabolism , Ovarian Follicle/pathology , Ovary/pathology , Ovary/physiopathology , Pregnancy , Proliferating Cell Nuclear Antigen/metabolism , Public-Private Sector Partnerships , Rats , Rats, Sprague-Dawley , Societies, Scientific , Weight Gain/drug effects
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