Protective effect of Onpi-to (TJ-8117) on the expression of apoptosis in 5/6 nephrectomized rats

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 throug...

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Published inNihon Jinzo Gakkai shi Vol. 39; no. 4; pp. 377 - 386
Main Authors HATTORI, Tomohisa, FUJITSUKA, Naoki, SHINDO, Shoichiro, KUROGI, Akiko
Format Journal Article
LanguageJapanese
Published Japan Japanese Society of Nephrology 1997
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ISSN0385-2385
1884-0728
DOI10.14842/jpnjnephrol1959.39.377

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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 dosedependent 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.
AbstractList 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.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.
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 dosedependent 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.
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.
Author SHINDO, Shoichiro
KUROGI, Akiko
HATTORI, Tomohisa
FUJITSUKA, Naoki
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References 15. Dworkin LD, Feiner HD, Parker M, Tolbert E. Effects of nifedipine and enalapril on glomerular structure and function in uninephrectomized SHR. Kidney Int 1991 ; 39 :1112-1117.
14. 塩之入洋,木原 実,成瀬雅彦,他.アンジオテンシン変換酵素阻害薬.腎と透析(増刊号)1995;39:563-572.
4. Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in progressive crescentic glomerulonenhritis. Lab Invest 1996 ; 74 : 941-951.
16. Dworkin LD, Benstein JA, Feiner HD, Parker M, Tolbert E. Calcium antagonist and converting enzyme inhibitors reduce renal injury by different mechanisms. Kidney Int 1993 ; 43 808-814.
2. Shimizu A, Kitamura H, Masuda Y, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int 1995 ; 47 : 114-121.
1. Baker AJ, Mooney A, Hughes J, Lombardi D, Johnson RJ, Savill J. Mesangial cell apoptosis : The major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest 1994 ; 94 : 2105-2116.
13. 吉村吾志夫,宇田 普.メサンギウム増殖性腎炎におけるアポトーシス関連分子発現とその意義医学の歩み1996;178:761-764.
10. 藤塚直樹,服部智久,進藤省一郎.5/6腎摘出ラットにおける糸球体の増殖変化に対するTJ-8117の作用とその活1生成分について.日腎会誌1995;37:162(Suppl).
11. 槇野博史,杉山 斉,柏原直樹.糸球体硬化進展過程におけるアポトーシス.医学の歩み1996;178:770-775.
8. Mistuma T, Yokozawa T, Oura H, Terasawa K. Rhubarb therapy in patients with chronic renal failure (Part 2) Japan J Nephrology 1987 ; 34 : 73-85.
9. moue M, Suzuki R, Koide T, Sakaguchi N, Ogihara Y, Yabu Y. Antioxidant, gallic acid, induces apoptosis in HL 60 RG cells. Biochem and Biophys Res Commun 1994; 204: 898-904.
5. 服部智久,藤塚直樹,黒木亮子,進藤省一郎.慢性腎不全モデルにおける糸球体増殖因子とアポトーシス発現の変動.日本腎臓学会誌1996;38:Suppl.85.
6. 服部智久,進藤省一郎,久田孝光,藤塚直樹,日比野智子,寺園芳樹,丸野政雄.抗体で惹起された糸球体メサンギウム障害に対するTJ-8117の効果日薬理誌1995;105:63-75.
7. 服部智久,藤塚直樹,黒木亮子,進藤省一郎.5/6腎摘モデルにおけるTGFβ1産生に対する温脾湯(TJ-8117)の効果.日腎会誌1996;38:475-483.
3. Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota Z. Apoptosis in glomerular sclerosis. Kidney Int 1996 ; 49 :103-111.
12. 寺田典生.アポトーシス関連遺伝子の腎内分布とその発現.医学の歩み1996;178:723-727.
References_xml – reference: 1. Baker AJ, Mooney A, Hughes J, Lombardi D, Johnson RJ, Savill J. Mesangial cell apoptosis : The major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest 1994 ; 94 : 2105-2116.
– reference: 3. Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota Z. Apoptosis in glomerular sclerosis. Kidney Int 1996 ; 49 :103-111.
– reference: 8. Mistuma T, Yokozawa T, Oura H, Terasawa K. Rhubarb therapy in patients with chronic renal failure (Part 2) Japan J Nephrology 1987 ; 34 : 73-85.
– reference: 6. 服部智久,進藤省一郎,久田孝光,藤塚直樹,日比野智子,寺園芳樹,丸野政雄.抗体で惹起された糸球体メサンギウム障害に対するTJ-8117の効果日薬理誌1995;105:63-75.
– reference: 9. moue M, Suzuki R, Koide T, Sakaguchi N, Ogihara Y, Yabu Y. Antioxidant, gallic acid, induces apoptosis in HL 60 RG cells. Biochem and Biophys Res Commun 1994; 204: 898-904.
– reference: 4. Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in progressive crescentic glomerulonenhritis. Lab Invest 1996 ; 74 : 941-951.
– reference: 10. 藤塚直樹,服部智久,進藤省一郎.5/6腎摘出ラットにおける糸球体の増殖変化に対するTJ-8117の作用とその活1生成分について.日腎会誌1995;37:162(Suppl).
– reference: 12. 寺田典生.アポトーシス関連遺伝子の腎内分布とその発現.医学の歩み1996;178:723-727.
– reference: 14. 塩之入洋,木原 実,成瀬雅彦,他.アンジオテンシン変換酵素阻害薬.腎と透析(増刊号)1995;39:563-572.
– reference: 15. Dworkin LD, Feiner HD, Parker M, Tolbert E. Effects of nifedipine and enalapril on glomerular structure and function in uninephrectomized SHR. Kidney Int 1991 ; 39 :1112-1117.
– reference: 11. 槇野博史,杉山 斉,柏原直樹.糸球体硬化進展過程におけるアポトーシス.医学の歩み1996;178:770-775.
– reference: 13. 吉村吾志夫,宇田 普.メサンギウム増殖性腎炎におけるアポトーシス関連分子発現とその意義医学の歩み1996;178:761-764.
– reference: 16. Dworkin LD, Benstein JA, Feiner HD, Parker M, Tolbert E. Calcium antagonist and converting enzyme inhibitors reduce renal injury by different mechanisms. Kidney Int 1993 ; 43 808-814.
– reference: 5. 服部智久,藤塚直樹,黒木亮子,進藤省一郎.慢性腎不全モデルにおける糸球体増殖因子とアポトーシス発現の変動.日本腎臓学会誌1996;38:Suppl.85.
– reference: 7. 服部智久,藤塚直樹,黒木亮子,進藤省一郎.5/6腎摘モデルにおけるTGFβ1産生に対する温脾湯(TJ-8117)の効果.日腎会誌1996;38:475-483.
– reference: 2. Shimizu A, Kitamura H, Masuda Y, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int 1995 ; 47 : 114-121.
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Snippet 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...
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SubjectTerms 5/6 nephrectomy, rats, TJ-8117, apoptosis, Bcl-2, Bax
Animals
Apoptosis - drug effects
Depression, Chemical
DNA Fragmentation - drug effects
Dose-Response Relationship, Drug
Drugs, Chinese Herbal - pharmacology
Kidney Glomerulus - cytology
Male
Nephrectomy
Rats
Rats, Wistar
Title Protective effect of Onpi-to (TJ-8117) on the expression of apoptosis in 5/6 nephrectomized rats
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