tretinoin and Rodent-Diseases

As a teratogenic agent retinoic acid (RA) produces severe limb reduction defects if administered at a certain stage of embryonic development. In vitro, RA is able to prevent chondrogenesis and this inhibitory effect is accompanied by the absence of cartilage specific proteoglycans in treated cultures. Such an effect is ruled out as a direct causative factor in teratogenesis for two reasons. First, the limbs of treated embryos show extensive chondrogenesis and this cartilage is normal as far as the expression of biochemical markers of differentiation are concerned. Second, the morphogenetic effects of a mutant gene, cmd, where there is a functional deficit of the proteoglycan core protein are very different from those associated with RA-induced teratogenesis. The differences between the two are not wholly reconciled by the fact that the effects of the mutant gene are cumulative and progressive while those of the RA insult are transitory. There are a number of developmental events which are, however, altered by RA in the mesenchymal cells of the early limb bud such as cell proliferation, cell death, and hyaluronic acid metabolism. Not only any one or more of these factors may secondarily inhibit chondrogenesis but, more importantly, may also have a number of other consequences in the developing embryo. Since a number of cell types besides mesenchymal cells respond to RA by altering their pattern of differentiation, it is conceivable that some fundamental molecular step in the process of differentiation provides a target for its action. In a recent review, Sporn and Roberts (1983) have suggested that to be compatible with the wide ranging effects of retinoids documented so far, any hypothesis put forward for its molecular mechanism of action must include a role in gene expression. No experimental work has yet directly addressed how retinoids might modify gene expression. We believe that along with teratocarcinoma stem cell lines, the use of retinoids as selective teratogens may open up another avenue in search of molecular mechanisms of cell differentiation.

Topics: Abnormalities, Drug-Induced; Animals; Cartilage; Cell Differentiation; Ectromelia; Extremities; Female; Glycosaminoglycans; Limb Deformities, Congenital; Mice; Mice, Inbred ICR; Mice, Mutant Strains; Pregnancy; Rodent Diseases; Tretinoin

Ischemic stroke is a severe neurodegenerative disease with a high mortality rate. Retinoic acid is a representative metabolite of vitamin A. It has many beneficial effects including anti-inflammatory, anti-apoptotic, and neuroprotective effects. The purpose of this study is to identify specific proteins that are regulated by retinoic acid in ischemic stroke. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle was injected intraperitoneally into male rats for four days prior to MCAO operation. Neurobehavioral tests were performed 24 hr after MCAO and the cerebral cortex was collected for proteomic study. Retinoic acid alleviates neurobehavioral deficits and histopathological changes caused by MCAO. Furthermore, we identified various proteins that were altered by retinoic acid in MCAO damage. Among these identified proteins, adenosylhomocysteinase, isocitrate dehydrogenase [NAD

Topics: Animals; Brain Ischemia; Infarction, Middle Cerebral Artery; Ischemic Stroke; Male; Neurodegenerative Diseases; Neuroprotective Agents; Proteins; Proteomics; Rats; Rats, Sprague-Dawley; Rodent Diseases; Tretinoin

The effect of milk on bone health is controversial. In this study, the effects of yak milk in mice with retinoic acid-induced osteoporosis (OP) were evaluated. Yak milk was provided to OP mice as a nutrition supplement for 6 wk. The results showed that yak milk significantly reduced bone turnover markers (tartrate acid phosphatase and alkaline phosphatase). The yak milk treatment was also associated with remarkably increased bone mineral density, bone volume, trabecular thickness, and trabecular number, as well as improved biomechanical properties (maximum load and stress) of the tibia. Furthermore, yak milk mitigated the deterioration of the network and thickness of trabecular bone in treated OP mice compared with the OP model group. The results indicated that yak milk could improve bone mass and microarchitecture through the inhibition of bone resorption in OP mice.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Cattle; Cattle Diseases; Mice; Milk; Osteoporosis; Rodent Diseases; Tartrates; Tretinoin