| Autor: |
Horita, Shoichiro, Watanabe, Guy, Misaka, Shingen, Taira, Shu, Satoh, Mamoru, Maejima, Yuko, Shimomura, Kenju, Shimabukuro, Michio, Kazama, Junichiro James, Shigetomi, Shuichi |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Renal Physiology; Oct2024, Vol. 327 Issue 4, pF581-F590, 10p |
| Abstrakt: |
Intrarenal dopamine plays a protective role against the development of diabetic nephropathy during the early stages of the disease. In streptozotocin-induced diabetic mice with renal-specific catechol-O-methyl transferase knockout, intrarenal dopamine was found to suppress glomerular hyperfiltration, reduce oxidative stress and inflammation, and inhibit fibrosis. However, although dopamine activation in streptozotocin-induced diabetic models has been shown to provide renal protection, the role of dopamine in models of naturally induced diabetes mellitus is still unclear. In the present study, we orally administered 10 mg/kg benserazide, a peripheral decarboxylase inhibitor, to spontaneously diabetic Torii rats daily to investigate the activation of the renal dopaminergic system during the progression of diabetic nephropathy. Our findings show that peripheral dopamine decreased urinary 8-iso-prostaglandin F2α and suppressed increases in plasma cystatin C levels. This study demonstrates that a reduction in peripheral dopamine can exacerbate renal dysfunction, even in the early stages of diabetic nephropathy characterized by glomerular hyperfiltration, thereby clarifying the pivotal role of endogenous peripheral dopamine in modulating oxidative stress and kidney performance. NEW & NOTEWORTHY: By administering a peripheral decarboxylase inhibitor, we revealed that peripheral dopamine inhibits both the increase in urinary 8-iso-prostaglandin F2α, an oxidative stress marker, and the increase in plasma cystatin C, an early renal dysfunction marker, even in the early stages of diabetic nephropathy characterized by glomerular hyperfiltration. By visualizing renal dopamine precursor distribution, we highlighted the role of endogenous renal dopamine in oxidative stress and renal function following the onset of glomerular hyperfiltration. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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