Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells.
The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production.
Horiguchi
Hyogo
H
Division of Environmental Medicine, Center for Community Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. hhyogo@jichi.ac.jp
Oguma
Etsuko
E
Kayama
Fujio
F
D000747:Anemia, Hypochromic / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D019256:Cadmium Chloride / Q000378:metabolism / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D004921:Erythropoietin / Q000097:blood / Q000378:metabolism*; D005260:Female; D006403:Hematologic Tests; D000860:Hypoxia / Q000378:metabolism; D017403:In Situ Hybridization; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D000970:Antineoplastic Agents; D004785:Environmental Pollutants; D012333:RNA, Messenger; D004921:Erythropoietin; D019256:Cadmium Chloride; D002945:Cisplatin