Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid

Okada, Shigeru; Hamazaki, Shuji; Ebina, Yoshihito; Li, Jiali; Midorikawa, Osamu

doi:10.1016/0005-2760(87)90241-4

Cited by 68 publications

(29 citation statements)

References 14 publications

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“…Results of earlier studies demonstrated that lipid peroxidation is closely associated with Fe-NTA-induced carcinogenesis (7)(8)(9)(10)(11)(12). The present study has clearly demonstrated that HNE is generated in renal proximal tubules of rats exposed to oxidative stress by Fe-NTA and that HNE reacts with cytoplasmic constituents that can be recognized by anti-HNE-protein antibody.…”

Section: Discussionsupporting

confidence: 72%

“…injections of Fe-NTA were reported to induce acute and subacute renal proximal tubular necrosis and a subsequent high incidence (60-92%) of renal adenocarcinoma in male rats and mice (4)(5)(6). We have shown in this model that lipid peroxidation as seen biochemically by thiobarbituric acid-reactive substances TBARS) and histochemically by the cold Schiffs method (detection of aldehydes) has been closely associated with carcinogenesis (7)(8)(9)(10)(11)(12). Lipid peroxidation has been implicated in causing a wide range ofbiological effects (13) including heart diseases, aging, retinal degeneration, and cancer.…”

Section: By _uans Of Anmentioning

confidence: 99%

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Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate.

Toyokuni

Uchida²,

Okamoto³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

324

194

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An iron chelate, ferric nitrilotriacetate (Fe-NTA), Induces prox l tubular necrosis, a consequence of lipid peroxidatlon, that iall leads to a high Incidence of renal adenocarcinoma in rodents. Lipid peroidation as monitored by formation of thiobarbituric acdd-reactive suaces and bee 4-hydroxy-2-noena (HNE) was observed in the kidney homogenates of rats treated with Fe-NTA. Based on the fact that HNE is capable of reating with cellular proteins, we attempted to detect the localization of HNE-mopie proteins in rat kidney tissues with an immustochemical procedure.

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Section: Discussionsupporting

confidence: 72%

Section: By _uans Of Anmentioning

confidence: 99%

Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate.

Toyokuni

Uchida²,

Okamoto³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

324

194

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“…An iron chelator, nitrilotriacetate, has been used in this fiberunassociated mesothelioma model to mobilize the catalytic form of iron from deposits. 23,24 Our study revealed a number of important implications regarding mesothelioma, which is a serious social problem in many countries following asbestos exposure. From an epidemiological standpoint, asbestos fibers, in particular, crocidolite and amosite, are recognized to be more carcinogenic when containing high amounts of iron.…”

Section: Discussionmentioning

confidence: 86%

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Akatsuka

Yamashita

et al. 2010

Laboratory Investigation

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In humans, mesothelioma has been linked to asbestos exposure, especially crocidolite and amosite asbestos, which contain high amounts of iron. Previously, we established a rat model of iron-induced peritoneal mesothelioma with repeated intraperitoneal injections of iron saccharate and an iron chelator, nitrilotriacetate. Here, we analyze these mesotheliomas using array-based comparative genomic hybridization (aCGH) and gene expression profiling by microarray. Mesotheliomas were classified into two distinct types after pathologic evaluation by immunohistochemistry. The major type, epithelioid mesothelioma (EM), originated in the vicinity of tunica vaginalis testis, expanded into the upper peritoneal cavity and exhibited papillary growth and intense podoplanin immunopositivity. The minor type, sarcomatoid mesothelioma (SM), originated from intraperitoneal organs and exhibited prominent invasiveness and lethality. Both mesothelioma types showed male preponderance. SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations. Uromodulin was highly expressed in most of the cases. After 4-week treatment, iron deposition in the mesothelia was observed with 8-hydroxy-2 0 -deoxyguanosine formation. These results not only show two distinct molecular pathways for iron-induced peritoneal mesothelioma, but also support the hypothesis that oxidative stress by iron overload is a major cause of CDKN2A/2B homozygous deletion.

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“…In our previous reports, we demonstrated that an iron chelate, ferric nitrilotriacetate (Fe-NTA), causes severe acute and subacute nephrotoxicity by lipid peroxidation (Hamazaki et al, 1985Okada et al, 1987;Li et al, 1988). This has recently been confirmed by others (Preece et al, 1988).…”

mentioning

confidence: 99%

Induction of mesothelioma by intraperitoneal injections of ferric saccharate in male Wistar rats

Okada

Hamazaki²,

Toyokuni³

et al. 1989

Br J Cancer

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Summary Iron appears to play a major role in catalysing free radical production, leading to lipid peroxidation and DNA damage. We, therefore, investigated the effect of colloidal iron deposited in the peritoneum. Wistar male rats were given either ferric saccharate, ferric saccharate and nitrilotriacetic acid (NTA), NTA or saline. NTA was shown previously to 'free' iron to promote lipid peroxidation and an iron chelate of NTA is known to be carcinogenic to the kidney. Iron at a dose of 5 mg kg-' day-', and saline at a dose of 0.5 ml day-' were injected i.p. for 3 months. NTA at a dose of 83.5 mg kg-' day-' was give i.p for 5 months. All the rats were killed about a year later for histological examination. In nine of the 19 rats treated with ferric saccharate, mesothelial tumors were induced in the serosa of the tunica vaginalis or the length of the spermatic cord. Among rats treated with ferric saccharate and NTA, seven had localised mesotheliomas in the above locations and six had wide-spread peritoneal mesotheliomas. No mesothelial tumors developed in either NTA treated or saline treated rats. No pleural mesotheliomas were found in any group. These findings add to the evidence that iron is involved in some carcinogenic processes.

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Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid

Cited by 68 publications

References 14 publications

Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate.

Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate.

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Induction of mesothelioma by intraperitoneal injections of ferric saccharate in male Wistar rats

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