title: Effects of thyroxine on hyperkalemia and renal cortical Na+, K+ - ATPase activity induced by cyclosporin A.
abstract: Cyclosporin A (CsA)-induced hyperkalemia is caused by alterations in transepithelial K+ secretion resulting from the inhibition of renal tubular Na+, K+ -ATPase activity. Thyroxine enhances renal cortical Na+, K+ -ATPase activity. This study investigated the effect of thyroxine on CsA-induced hyperkalemia. Sprague-Dawley rats were treated with either CsA, thyroxine, CsA and thyroxine, or olive-oil vehicle. CsA resulted in an increase in BUN and serum K+, along with a decrease in creatinine clearance, fractional excretion of potassium, and renal cortical Na+, K+ -ATPase activity, as compared with oil vehicle administration. Histochemical study showed reduced Na+, K+ -ATPase activity in the proximal tubular epithelial cells of the CsA-treated compared with the oil-treated rats. Histologically, isometric intracytoplasmic vacuolation, disruption of the arrangement and swelling of the mitochondria, and a large number of lysosomes in the tubular epithelium were characteristic of the CsA-treated rats. Co-administration of thyroxine prevented CsA-induced hyperkalemia and reduced creatinine clearance, Na+, K+ -ATPase activity, and severity of the histologic changes in the renal tubular cells when compared with the CsA-treated rats. Thyroxine increased the fractional excretion of potassium via the preservation of Na+, K+ -ATPase activity in the renal tubular cells. Thus, the beneficial effects of thyroxine may be suited to treatment modalities for CsA-induced hyperkalemia.
authors.affiliation: Department of Pediatrics, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Chur-Woo
authors.initials: CW
authors.lastname: You
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Park
authors.forename: Eun-Sil
authors.initials: ES
authors.lastname: Lee
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Son-Moon
authors.initials: SM
authors.lastname: Shin
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Park
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006947:Hyperkalemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D011188:Potassium / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000254:Sodium-Potassium-Exchanging ATPase; D013974:Thyroxine; D011188:Potassium