- 著者
-
山本 秀樹
矢本 敬
真鍋 淳
- 出版者
- 日本毒性学会
- 雑誌
- 日本トキシコロジー学会学術年会 第33回日本トキシコロジー学会学術年会
- 巻号頁・発行日
- pp.21, 2006 (Released:2006-06-23)
a) PPAR alphaThe use of PPAR-null mice revealed that PPAR alpha is required to mediate hepatomegaly and subsequent hepatocarcinogenesis in rodents. Human PPAR alpha appears to be different in function as compared to the rodent isoforms. The fundamental roles of PPAR alpha in reproductive toxicity reported in some environmental contaminants (e.g., phthaletes), in myopathy mainly reported in fibrates and in heart pathophysiology have not been fully understood to date.b) PPAR gammaSynthetic PPAR gamma agonists cause weight gain due to both fat deposit and fluid retention in both human and experimental animals. The fluid retention is thought to contribute to an increase in heart weight and edema observed after PPAR gamma agonist treatment. Recent studies using rodents reveal that PPAR gamma-dependent upregulation of renal sodium transport protein secondarily influences fluid retention and increases in body mass and heart weight. However, it is unclear whether this mechanism is relevant to the clinical situation in humans or not. PPAR gamma-dependent enhanced adipogenesis in bone marrow leads to hypocellularity and consequently affects hematopoiesis. c) PPAR beta/deltaToxicity information for PPAR beta/delta agonists is not as well characterized as compared to that for PPAR alpha and PPAR gamma agonists. There is evidence suggesting that PPAR beta/delta is involved in valproic acid-induced developmental toxicity. Furthermore, recent studies shows PPAR beta/delta may be implicated in hepatic stellate cell proliferation and liver fibrosis.