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[Protective effect of onpi-to (TJ-8117) on the expression of apoptosis in 5/6 nephrectomized rats]
T Hattori1, N Fujitsuka, A Kurogi
1TSUMURA and Co. Central Laboratories, New Drug Research Department 1, Ibaraki, Japan.
Abstract:
The present study was designed to clarify the effects of TJ-8117 on apoptosis in the glomeruli of 5/6 nephrectomized rats. TJ-8117 (400 mg/kg/day), captopril (50 mg/kg/day) and nicardipine (50 mg/kg/day) were administered as drinking water from the 56th day after renal ablation, and continued throughout the experiment. All rats were sacrificed at 13 weeks and renal tissues were removed to quantify histopathological and apoptotic parameters in glomeruli. TJ-8117 inhibited proteinuria, matrix index and decrease in the number of total cells in glomeruli of nephrectomized rats. In addition, the increase in apoptotic body and DNA fragmentation was significantly inhibited in the TJ-8117-treated group. Captopril and nicardipine failed to inhibit both parameters. In 400 mg/kg of the TJ-8117 treated group, the number of Bcl -2 positive cells in the glomeruli was elevated compared with the 5/6 nephrectomized control group. In addition, the number of Bax positive cells in the TJ-8117 group was significantly suppressed in a dose-dependent manner. These results suggest that TJ-8117 may inhibit apoptosis in the late stage of this model by suppressing matrix accumulation and progression of glomerulosclerosis. The apoptosis-preventing effect may be mediated by decreased expression of Bax in the glomerular cells.
Insights
TJ-8117 significantly inhibited glomerular apoptosis and reduced matrix accumulation in nephrectomized rats, unlike captopril and nicardipine. This suggests TJ-8117 protects against glomerulosclerosis progression.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Context:
- Chronic kidney disease models are crucial for understanding disease progression.
- Glomerulosclerosis is a hallmark of progressive kidney damage.
- Apoptosis plays a significant role in the pathogenesis of kidney disease.
Purpose:
- To investigate the effects of TJ-8117 on glomerular apoptosis in a rat model of 5/6 nephrectomy.
- To compare the efficacy of TJ-8117 with established treatments like captopril and nicardipine.
- To elucidate the molecular mechanisms underlying TJ-8117's renoprotective effects.
Summary:
- TJ-8117 administration significantly reduced proteinuria, matrix index, and glomerular cell loss in nephrectomized rats.
- The compound markedly inhibited the increase in apoptotic bodies and DNA fragmentation.
- TJ-8117 upregulated Bcl-2 and dose-dependently suppressed Bax expression in glomeruli, unlike captopril and nicardipine.
Impact:
- TJ-8117 demonstrates potential as a therapeutic agent for inhibiting glomerulosclerosis progression.
- The drug's apoptosis-preventing effect, possibly mediated by Bax suppression, offers a novel therapeutic strategy.
- These findings contribute to the development of new treatments for chronic kidney disease.