Effects of Thyroxine on Hyperkalemia and Renal Cortical Na(+), K(+) - ATPase Activity Induced by Cyclosporin A.
10.3346/jkms.2002.17.5.625
- Author:
Chur Woo YOU
1
;
Yong Hoon PARK
;
Eun Sil LEE
;
Yong Jin KIM
;
Son Moon SHIN
;
Mi Ok PARK
Author Information
1. Department of Pediatrics, College of Medicine, Konyang University, Daejeon, Korea. yhpark@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Cyclosporin A;
Hyperkalemia;
Thyroxine;
Renal Corex;
Na(+);
K(+)-ATPase
- MeSH:
Animals;
Cyclosporine/antagonists & inhibitors/*toxicity;
Hyperkalemia/chemically induced/*drug therapy/metabolism/prevention & control;
Immunosuppressive Agents/antagonists & inhibitors/*toxicity;
Kidney Cortex/*drug effects/*enzymology/pathology;
Male;
Microsomes/enzymology;
Potassium/blood/metabolism;
Rats;
Rats, Sprague-Dawley;
Sodium-Potassium-Exchanging ATPase/*metabolism;
Thyroxine/*pharmacology
- From:Journal of Korean Medical Science
2002;17(5):625-632
- CountryRepublic of Korea
- Language:English
-
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.
