Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9000639 | Experimental and Toxicologic Pathology | 2005 | 10 Pages |
Abstract
Streptozotocin (SZ) is known to exert toxic effects not only on pancreatic islet beta cells but also on other organs including liver. For analyzing changes in genes expression associated with SZ toxicity, we performed DNA microarray analyses on the liver obtained from SZ-treated mice. Eight-week-old male ICR mice were treated i.p. with 200Â mg/kg of SZ, and the blood and liver were taken at 6, 24 and 48Â h after the treatment. Labeled cRNA prepared from total RNA of the liver was hybridized to the GeneChip Murine Genome U74A V.2 (Affymetrix). The number of the probe sets, which were clearly up-regulated or down-regulated, were over 100 at 6 and 24Â h after the SZ-treatment, and it decreased at 48Â h after the treatment. Many of the up-regulated genes were categorized into cell cycle/apoptosis related genes, immune/allergy related genes and stress response/xenobiotic metabolism related genes. On the other hand, genes related to glucose, lipid and protein metabolisms were down-regulated. These changes started prior to the elevation of the serum glucose levels, indicating the direct action of SZ on the liver rather than the secondary effect of diabetes. This may be related with the previously reported hepatic changes such as lipid peroxidation, mitochondrial swelling and inhibition of hepatocyte proliferation observed before the development of hyperglycemia (Exp. Toxic Pathol. 55 (2004) 467)
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Authors
Eisuke Kume, Chinami Aruga, Yukito Ishizuka, Kaori Takahashi, Satoko Miwa, Masahito Itoh, Hisako Fujimura, Wataru Toriumi, Kazuyuki Kitamura, Kunio Doi,