The Experts below are selected from a list of 3135 Experts worldwide ranked by ideXlab platform
Kenjiro Kimura - One of the best experts on this subject based on the ideXlab platform.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine induced renal injury
American Journal of Physiology-renal Physiology, 2016Co-Authors: Atsuko Kamijoikemori, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Kazuaki Hirata, Mikako Hisamichi, Kenjiro KimuraAbstract:The aim of the present study was to reveal the Effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury...
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.
Takeshi Sugaya - One of the best experts on this subject based on the ideXlab platform.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat under decreased angiotensin ii type 1a receptor expression
European Journal of Pharmacology, 2017Co-Authors: Keiichi Ohata, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Junko AsanoAbstract:The aim of this study was to confirm the Renoprotective Effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1a (AT1a) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1a expression, we used AT1a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1a+/-L-FABP+/-). Male AT1a+/-L-FABP+/- mice were divided into two groups: the adenine diet group (n = 40) was given a diet containing only 0.2% w/w adenine, and the normal diet group (n = 5) was given a normal diet. When renal dysfunction was confirmed in the adenine diet group 4 weeks after starting the diet, the adenine diet group was further divided into five groups. The adenine diet group (n = 8) was continuously given only the adenine diet. Each group receiving high-dose (3mg/kg) or low-dose (1mg/kg) topiroxostat (Topiroxostat-H group, n = 8, Topiroxostat-L group, n = 8) or febuxostat (Febuxostat-H group, n = 8, Febuxostat-L group, n = 8) was given the adenine diet including the drug for another 4 weeks. The levels of renal XOR, renal dysfunction, urinary L-FABP, tubulointerstitial damage, hypoxia, and oxidative stress were decreased or attenuated after treatment with topiroxostat or febuxostat compared with the adenine diet group. Furthermore, antioxidant capacity was maintained owing to these treatments. In conclusion, topiroxostat and febuxostat attenuated renal damage under decreased AT1a expression in the adenine-induced renal injury model.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine induced renal injury
American Journal of Physiology-renal Physiology, 2016Co-Authors: Atsuko Kamijoikemori, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Kazuaki Hirata, Mikako Hisamichi, Kenjiro KimuraAbstract:The aim of the present study was to reveal the Effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.
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Renoprotective Effect of dpp 4 inhibitors against free fatty acid bound albumin induced renal proximal tubular cell injury
Biochemical and Biophysical Research Communications, 2016Co-Authors: Yuki Tanaka, Takeshi Sugaya, Shinji Kume, Masami Chinkanasaki, Hisazumi Araki, Shinichi Araki, Satoshi Ugi, Takashi Uzu, Hiroshi MaegawaAbstract:Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic Effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the Renoprotective Effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct Renoprotective Effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy.
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury...
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.
Atsuko Kamijoikemori - One of the best experts on this subject based on the ideXlab platform.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat under decreased angiotensin ii type 1a receptor expression
European Journal of Pharmacology, 2017Co-Authors: Keiichi Ohata, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Junko AsanoAbstract:The aim of this study was to confirm the Renoprotective Effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1a (AT1a) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1a expression, we used AT1a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1a+/-L-FABP+/-). Male AT1a+/-L-FABP+/- mice were divided into two groups: the adenine diet group (n = 40) was given a diet containing only 0.2% w/w adenine, and the normal diet group (n = 5) was given a normal diet. When renal dysfunction was confirmed in the adenine diet group 4 weeks after starting the diet, the adenine diet group was further divided into five groups. The adenine diet group (n = 8) was continuously given only the adenine diet. Each group receiving high-dose (3mg/kg) or low-dose (1mg/kg) topiroxostat (Topiroxostat-H group, n = 8, Topiroxostat-L group, n = 8) or febuxostat (Febuxostat-H group, n = 8, Febuxostat-L group, n = 8) was given the adenine diet including the drug for another 4 weeks. The levels of renal XOR, renal dysfunction, urinary L-FABP, tubulointerstitial damage, hypoxia, and oxidative stress were decreased or attenuated after treatment with topiroxostat or febuxostat compared with the adenine diet group. Furthermore, antioxidant capacity was maintained owing to these treatments. In conclusion, topiroxostat and febuxostat attenuated renal damage under decreased AT1a expression in the adenine-induced renal injury model.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine induced renal injury
American Journal of Physiology-renal Physiology, 2016Co-Authors: Atsuko Kamijoikemori, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Kazuaki Hirata, Mikako Hisamichi, Kenjiro KimuraAbstract:The aim of the present study was to reveal the Effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury...
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.
Seiko Hoshino - One of the best experts on this subject based on the ideXlab platform.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat under decreased angiotensin ii type 1a receptor expression
European Journal of Pharmacology, 2017Co-Authors: Keiichi Ohata, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Junko AsanoAbstract:The aim of this study was to confirm the Renoprotective Effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1a (AT1a) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1a expression, we used AT1a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1a+/-L-FABP+/-). Male AT1a+/-L-FABP+/- mice were divided into two groups: the adenine diet group (n = 40) was given a diet containing only 0.2% w/w adenine, and the normal diet group (n = 5) was given a normal diet. When renal dysfunction was confirmed in the adenine diet group 4 weeks after starting the diet, the adenine diet group was further divided into five groups. The adenine diet group (n = 8) was continuously given only the adenine diet. Each group receiving high-dose (3mg/kg) or low-dose (1mg/kg) topiroxostat (Topiroxostat-H group, n = 8, Topiroxostat-L group, n = 8) or febuxostat (Febuxostat-H group, n = 8, Febuxostat-L group, n = 8) was given the adenine diet including the drug for another 4 weeks. The levels of renal XOR, renal dysfunction, urinary L-FABP, tubulointerstitial damage, hypoxia, and oxidative stress were decreased or attenuated after treatment with topiroxostat or febuxostat compared with the adenine diet group. Furthermore, antioxidant capacity was maintained owing to these treatments. In conclusion, topiroxostat and febuxostat attenuated renal damage under decreased AT1a expression in the adenine-induced renal injury model.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine induced renal injury
American Journal of Physiology-renal Physiology, 2016Co-Authors: Atsuko Kamijoikemori, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Kazuaki Hirata, Mikako Hisamichi, Kenjiro KimuraAbstract:The aim of the present study was to reveal the Effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury...
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.
Kimie Katayama - One of the best experts on this subject based on the ideXlab platform.
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Renoprotective Effect of the xanthine oxidoreductase inhibitor topiroxostat under decreased angiotensin ii type 1a receptor expression
European Journal of Pharmacology, 2017Co-Authors: Keiichi Ohata, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Junko AsanoAbstract:The aim of this study was to confirm the Renoprotective Effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1a (AT1a) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1a expression, we used AT1a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1a+/-L-FABP+/-). Male AT1a+/-L-FABP+/- mice were divided into two groups: the adenine diet group (n = 40) was given a diet containing only 0.2% w/w adenine, and the normal diet group (n = 5) was given a normal diet. When renal dysfunction was confirmed in the adenine diet group 4 weeks after starting the diet, the adenine diet group was further divided into five groups. The adenine diet group (n = 8) was continuously given only the adenine diet. Each group receiving high-dose (3mg/kg) or low-dose (1mg/kg) topiroxostat (Topiroxostat-H group, n = 8, Topiroxostat-L group, n = 8) or febuxostat (Febuxostat-H group, n = 8, Febuxostat-L group, n = 8) was given the adenine diet including the drug for another 4 weeks. The levels of renal XOR, renal dysfunction, urinary L-FABP, tubulointerstitial damage, hypoxia, and oxidative stress were decreased or attenuated after treatment with topiroxostat or febuxostat compared with the adenine diet group. Furthermore, antioxidant capacity was maintained owing to these treatments. In conclusion, topiroxostat and febuxostat attenuated renal damage under decreased AT1a expression in the adenine-induced renal injury model.
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury...
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Renoprotective Effect of renal liver type fatty acid binding protein and angiotensin ii type 1a receptor loss in renal injury caused by ras activation
American Journal of Physiology-renal Physiology, 2014Co-Authors: Daisuke Ichikawa, Takeshi Sugaya, Seiko Hoshino, Atsuko Kamijoikemori, Kimie Katayama, Yugo Shibagaki, Takashi Yasuda, Junko Igarashimigitaka, Kazuaki Hirata, Kenjiro KimuraAbstract:The aim of this study was to assess the Renoprotective Effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.
