Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Impact of the protection from free radical injury in heat shock preconditioning against ischemia-reperfusion injury in steatotic rat livers.

Yamagami, K; Yamamoto, Y; Kume, M; Kimoto, S; Ozaki, N; Toyokuni, S; Yamaoka, Y

HEPATOLOGY Vol. 26 ( 4 ) page： 844 - 844 1997.10

Impact of the protection from free radical injury in heat shock preconditioning against ischemia-reperfusion injury in steatotic rat livers.

Yamagami K, Yamamoto Y, Kume M, Kimoto S, Ozaki N, Toyokuni S, Yamaoka Y

HEPATOLOGY Vol. 26 ( 4 ) page： 844 - 844 1997.10

Enhanced hepatic lipid peroxidation in chronic hepatitis C [abstract]. Reviewed International journal

KAGEYAMA F.

Hepatology Vol. 26 ( 4 ) page： 79 - 79 1997.10

Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: Independence of tubular necrosis and sulfhydryl depletion

Tanaka T., Nishiyama Y., Okada K., Hirota K., Matsui M., Yodoi J., Hiai H., Toyokuni S.

Laboratory Investigation Vol. 77 ( 2 ) page： 145 - 155 1997.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Laboratory Investigation

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin (TRX). ADF/TRX is a conserved multifunctional reductant presumably associated with redox regulation of the cellular environment; it works in vitro as a cytokine, free radical scavenger, activator of transcription factors, and substrate for several enzymes. In the present series of experiments, we studied the expression and intracellular localization of ADF/TRX in mouse kidney from two different renal tubular injury models: a free radical-associated model with ferric nitrilotriacetate (Fe-NTA) and a free radical-independent model with HgCI2. Markers of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine, thiobarbituric acid-reactive substances, and 4-hydroxy-2-nonenal-modified proteins, were significantly increased in kidney from male C57BL/6 mice 1 hour after a single intraperitoneal injection of Fe-NTA (5 mg iron/kg). However, in kidney from mice given a subcutaneous injection of HgCI2 (5 mg Hg/kg), none of these markers were increased, despite tubular necrosis with sulfhydryl depletion. In the Fe-NTA model only, Northern and Western blot analyses of the kidney revealed induction of ADF/TRX (> 2.5-fold) after 16 hours and translocation of ADF/TRX from the cytoplasmic to nuclear fraction (> 3.5-fold) after 24 hours. Immunohistochemistry showed a catchy distribution of ADF/TRX in the normal renal proximal tubules. In ex vivo experiments using serial normal kidney frozen sections, it was found mat renal proximal tubules with low expression of ADF/FRX were more vulnerable to oxidative stress mediated by Fe-NTA. Collectively, these data suggest that: (a) ADF/TRX is induced and translocated to nuclei by oxidative damage mediated by Fe-NTA in the renal proximal tubules: (b) induction of ADF/TRX is independent of tubular necrosis or sulfhydryl depletion; and (c) ADF/TRX is involved in the cellular defense mechanisms in vive against oxidative damage.

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Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: Independence of tubular necrosis and sulfhydryl depletion

Tanaka T, Nishiyama Y, Okada K, Hirota K, Matsui M, Yodoi J, Hiai H, Toyokuni S

LABORATORY INVESTIGATION Vol. 77 ( 2 ) page： 145 - 155 1997.8

Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: independence of tubular necrosis and sulfhydryl depletion.

Tanaka T, Nishiyama Y, Okada K, Hirota K, Matsui M, Yodoi J, Hiai H, Toyokuni S

Laboratory investigation; a journal of technical methods and pathology Vol. 77 ( 2 ) page： 145 - 55 1997.8

Biomarker evidence of DNA oxidation in lung cancer patients: Association of urinary 8-hydroxy-2'-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment

Erhola M., Toyokuni S., Okada K., Tanaka T., Hiai H., Ochi H., Uchida K., Osawa T., Nieminen M.M., Alho H., Kellokumpu-Lehtinen P.

FEBS Letters Vol. 409 ( 2 ) page： 287 - 291 1997.6

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：FEBS Letters

Ratios of urinary 8-hydroxy-2'-deoxyguanosine to urinary creatinine (8-OHdG/creatinine) have been considered as a good biological indicator of DNA oxidation. Urinary 8-OHdG/creatinine levels of lung cancer patients were evaluated by enzyme-linked immunosorbent assay using a monoclonal antibody N45.1 during radiotherapy and chemotherapy. An increase in urinary 8-OHdG/creatinine was found in non-small-cell carcinoma (non-SCC) patients during the course of radiotherapy. SCC patients showed higher levels of urinary 8-OHdG/creatinine than the controls. Furthermore, SCC patients with complete or partial response to the chemotherapy showed a significant decrease in urinary 8-OHdG/creatinine while patients with no change or progressive disease showed an increase.

DOI： 10.1016/S0014-5793(97)00523-1

Scopus

Biomarker evidence of DNA oxidation in lung cancer patients: Association of urinary 8-hydroxy-2'-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment

Erhola M, Toyokuni S, Okada K, Tanaka T, Hiai H, Ochi H, Uchida K, Osawa T, Nieminen MM, Alho H, KellokumpuLehtinen P

FEBS LETTERS Vol. 409 ( 2 ) page： 287 - 291 1997.6

Protection by αG-Rutin, a Water-soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

SHIMOI Kayoko, SHEN Bingrong, TOYOKUNI Shinya, MOCHIZUKI Rika, FURUGORI Michiyo, KINAE Naohide

Jpn. J. Cancer Res. Vol. 88 ( 5 ) page： 453 - 460 1997.5

Protection by αG-Rutin, a Water-soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

SHIMOI Kayoko, SHEN Bingrong, TOYOKUNI Shinya, MOCHIZUKI Rika, FURUGORI Michiyo, KINAE Naohide

Japanese journal of cancer research : gann Vol. 88 ( 5 ) page： 453 - 460 1997.5

Protection by alpha G-rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate

Shimoi K, Shen BR, Toyokuni S, Mochizuki R, Furugori M, Kinae N

JAPANESE JOURNAL OF CANCER RESEARCH Vol. 88 ( 5 ) page： 453 - 460 1997.5

Protection by αG-Rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate

Shimoi K., Shen B., Toyokuni S., Mochizuki R., Furugori M., Kinae N.

Japanese Journal of Cancer Research Vol. 88 ( 5 ) page： 453 - 460 1997.5

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Cancer Research

The protective effect of αG-Rutin against ferric nitrilotriacetate (Fe-NTA)-induced renal damage was studied in male ICR mice. Fe-NTA induces renal lipid peroxidation, leading to a high incidence of renal cell carcinoma in rodents. Administration of αG-Rutin (50 μmol as rutin/kg) by gastric intubation 30 min after i.p. injection of Fe-NTA (7 mg Fe/kg) most effectively suppressed renal lipid peroxidation. Repeated i.p. injection of Fe-NTA (2 mg Fe/kg/day for the first 3 days and 3 mg Fe/kg/day for 12 days, 5 days a week) causes subacute nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal tubules. A protective effect was observed in mice given αG-Rutin 30 min after each Fe-NTA treatment. To elucidate the mechanism of protection by αG-Rutin, the pharmacokinetics and hydroxyl radical-scavenging effect of αG-Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), respectively. When mice were given αG-Rutin (50 μmol as rutin/kg) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of αG-Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min. αG-Rutin inhibited the formation of DMPO-OH in a concentration-dependent manner. Further, chelating activity of αG-Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed αG-Rutin works as an antioxidant in vivo either by scavenging reactive oxygen species or by chelating ferric ions and this serves to prevent oxidative renal damage in mice treated with Fe-NTA.

DOI： 10.1111/j.1349-7006.1997.tb00403.x

Scopus

Protection by alpha G-rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate

Shimoi K, Shen BR, Toyokuni S, Mochizuki R, Furugori M, Kinae N

JAPANESE JOURNAL OF CANCER RESEARCH Vol. 88 ( 5 ) page： 453 - 460 1997.5

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats Reviewed International journal

Ma YX, Zhang DX, Kawabata T, Kiriu T, Toyokuni S, Uchida K, Okada S

PATHOLOGY INTERNATIONAL Vol. 47 ( 4 ) page： 203 - 208 1997.4

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats

MA Yuxiang, ZHANG Daxian, KAWABATA Teruyuki, KIRIU Takahiro, TOYOKUNI Shinya, UCHIDA Koji, OKADA Shigeru

Pathology International Vol. 47 ( 4 ) page： 203 - 208 1997.4

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats Reviewed

YX Ma, DX Zhang, T Kawabata, T Kiriu, S Toyokuni, K Uchida, S Okada

PATHOLOGY INTERNATIONAL Vol. 47 ( 4 ) page： 203 - 208 1997.4

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL SCIENCE

The copper and iron status in the liver of non-tumor bearing Long-Evans Cinnamon (LEC) rats (average age 17 months) was investigated. A direct quantitation of loosely-bound copper anti iron was also investigated by using a chelating agent, nitrilotriacetic acid (NTA-chelatable free copper and iron). Besides the total copper and iron contents, the level of NTA-chelatable free copper was also higher in LEC rats than in LEA rats (P<0.05). But for the free iron level there was no significant difference between the two rat groups (P>0.05). The formation of thiobarbituric acid-reactive substances was higher in LEC rats than in LEA mts (P<0.01). The 4-hydroxy-2-nonenal (HNE)-modified proteins were also clearly demonstrated in LEC rat liver. The copper and iron which produced the most important effect in the process of oxidative damage in LEC rats could not be distinguished. Even though free copper, which could induce free radical injuries, was increased in LEC rats, neither tumor-induction nor preneoplastic lesions in the experimental LEC rats were observed. therefore it is speculated that the elevation of a free iron is another important factor. Copper and iron, both important transition metals In the body, may participate in the induction of DNA damage and oncogenesis.

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Quantitative immunohistochemical determination of 8-hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: Its application to ferric nitrilotriacetate-induced renal carcinogenesis model Reviewed International journal

Toyokuni S, Tanaka T, Hatton Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T

LABORATORY INVESTIGATION Vol. 76 ( 3 ) page： 365 - 374 1997.3

Toyokuni S, Tanaka T, Hatton Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T

LABORATORY INVESTIGATION Vol. 76 ( 3 ) page： 365 - 374 1997.3

Quantitative immunohistochemical determination of 8-hydroxy-2'- deoxyguanosine by a monoclonal antibody N45.1: Its application to ferric nitrilotriacetate-induced renal carcinogenesis model

Toyokuni S., Tanaka T., Hattori Y., Nishiyama Y., Yoshida A., Uchida K., Hiai H., Ochi H., Osawa T.

Laboratory Investigation Vol. 76 ( 3 ) page： 365 - 374 1997.3

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Laboratory Investigation

The DNA base-modified product 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most commonly used markers for the evaluation of oxidative DNA damage. A monoclonal antibody specific for 8-OHdG (N45.1) was characterized end applied in quantitative immunohistochemistry. N45.1 recognized both the modified base and deoxyribose structure of 8-OHdG and required a concentration two orders higher of 8-hydroxyguanosine as a competitor in the ELISA. In addition, N45.1 did not cross-react with the original four deoxyribonucleosides, other DNA base-modified products such as 8-hydroxy-2'- deoxyadenosine and O6-methyl-2'-deoxyguanosine, or urine components such as uric acid, creatine, and creatinine. A ferric nitrilotriacetate-induced rat renal carcinogenesis model was used for the evaluation of quantitative immunohistochemistry. The 8-OHdG index of quantitative immunohistochemistry, as analyzed by NIH Image freeware, correlated reasonably well with the 8- OHdG amount determined by high-performance liquid chromatography with an electrochemical detector-except for a difference in peak time, which could be attributed to the selection of target location. The present method has advantages over the high-performance liquid chromatography/electrochemical detector, gas chromatography/mass spectrometry, and 32P-postlabeling methods in that it allows localization of 8-OHdG to be specified without the risk of artifactual production of 8-OHdG during the DNA extraction and hydrolytic processes.

Scopus

Quantitative immunohistochemical determination of 8-hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model.

Toyokuni S, Tanaka T, Hattori Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T

Laboratory investigation; a journal of technical methods and pathology Vol. 76 ( 3 ) page： 365 - 74 1997.3

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