Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium

Shugo Suzuki, Lora L Arnold, Karen L. Pennington, Satoko Kakiuchi-Kiyota, Baowei Chen, Xiufen Lu, X. Chris Le, Samuel Monroe Cohen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100ppm AsV. DMPS (2800ppm) co-administered in the diet significantly reduced the AsV-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA.

Original languageEnglish (US)
Pages (from-to)155-159
Number of pages5
JournalToxicology
Volume299
Issue number2-3
DOIs
StatePublished - Sep 28 2012

Fingerprint

Arsenicals
Dietary Sodium
Sulfonic Acids
Rats
Urinary Bladder
Epithelium
Urothelium
Arsenic
Urine
Cytotoxicity
Methylation
Oxidative stress
Cell proliferation
Bromodeoxyuridine
Nutrition
Chelating Agents
Heavy Metals
Carcinogens
Electron Scanning Microscopy
Labeling

Keywords

  • 2,3-Dimercaptopropane-1-sulfonic acid (DMPS)
  • Arsenate (As)
  • Urinary bladder
  • Urothelial cell cytotoxicity

ASJC Scopus subject areas

  • Toxicology

Cite this

Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium. / Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L.; Kakiuchi-Kiyota, Satoko; Chen, Baowei; Lu, Xiufen; Le, X. Chris; Cohen, Samuel Monroe.

In: Toxicology, Vol. 299, No. 2-3, 28.09.2012, p. 155-159.

Research output: Contribution to journalArticle

Suzuki, Shugo ; Arnold, Lora L ; Pennington, Karen L. ; Kakiuchi-Kiyota, Satoko ; Chen, Baowei ; Lu, Xiufen ; Le, X. Chris ; Cohen, Samuel Monroe. / Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium. In: Toxicology. 2012 ; Vol. 299, No. 2-3. pp. 155-159.
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AU - Suzuki, Shugo

AU - Arnold, Lora L

AU - Pennington, Karen L.

AU - Kakiuchi-Kiyota, Satoko

AU - Chen, Baowei

AU - Lu, Xiufen

AU - Le, X. Chris

AU - Cohen, Samuel Monroe

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N2 - Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100ppm AsV. DMPS (2800ppm) co-administered in the diet significantly reduced the AsV-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA.

AB - Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100ppm AsV. DMPS (2800ppm) co-administered in the diet significantly reduced the AsV-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA.

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