1.Effects of Thyroxine on Hyperkalemia and Renal Cortical Na(+), K(+) - ATPase Activity Induced by Cyclosporin A.
Chur Woo YOU ; Yong Hoon PARK ; Eun Sil LEE ; Yong Jin KIM ; Son Moon SHIN ; Mi Ok PARK
Journal of Korean Medical Science 2002;17(5):625-632
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.
Animals
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Cyclosporine/antagonists & inhibitors/*toxicity
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Hyperkalemia/chemically induced/*drug therapy/metabolism/prevention & control
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Immunosuppressive Agents/antagonists & inhibitors/*toxicity
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Kidney Cortex/*drug effects/*enzymology/pathology
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Male
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Microsomes/enzymology
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Potassium/blood/metabolism
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Rats
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Rats, Sprague-Dawley
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Sodium-Potassium-Exchanging ATPase/*metabolism
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Thyroxine/*pharmacology
2.Antifibrotic effect of the Chinese herbs Modified Danggui Buxue Decoction on adriamycin-induced nephropathy in rats.
Ming-Gang WEI ; Wei SUN ; Pei-Hua XIONG ; Jia-de SHAO
Chinese journal of integrative medicine 2012;18(8):591-598
OBJECTIVETo investigate the antifibrotic effect of the Chinese herbs Modified Danggui Buxue Decoction (, MDBD) on adraimycin-induced nephropathy in rats.
METHODSThirty-two male Sprague Dawley albino rats were randomly divided into 4 groups: the control, model, and two treatment groups, with 8 in each group. Nephropathy was induced in the latter 3 groups by intravenous injection of adriamycin. Rats in the two treatment groups received intragastric administration of benazepri (a positive control) or MDBD, which is composed of extracts of Radix Angelicae sinensis, Astragalus membranaceus (Fisch.) Bge and Rhizoma chuanxiong. Serum albumin, blood lipids, 24-h urine protein and urine N-acetyl-b-D-glucosaminidase (NAG) were measured every 2 weeks. The ratio of kidney to body weight was measured. The expressions of extracellular matrix proteins in the renal cortex, including colleagen IV (Col-IV) and fibronectin (FN), were examined by immunohistochemistry, and the transcription of genes encoding transforming growth factor β1 (TGF-β1), the tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 9 (MMP-9) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) at the end of the 8-week treatment.
RESULTSCompared with the untreated rats in the model group, MDBD significantly increased serum albumin, lowered the blood lipids and decreased the ratio of kidney to body weight. MDBD significantly reduced the excretion levels of urinary protein and NAG as well as the accumulation of extracellular matrix (ECM), including Col-IV and FN, in the renal cortex. Further, MDBD decreased TIMP-1 and TGF-β1 gene expressions and increased MMP-9 gene expression in the kidney.
CONCLUSIONSMDBD was effective in treating the rat model of nephropathy. The clinical benefit was associated with reduction of renal fibrosis. The antifibrotic effect of MDBD may be mediated through the regulation of TIMP-1, MMP and TGF-β1 gene expressions.
Acetylglucosaminidase ; urine ; Animals ; Body Weight ; drug effects ; Collagen Type IV ; metabolism ; Doxorubicin ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fibronectins ; metabolism ; Fibrosis ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Kidney Cortex ; drug effects ; enzymology ; pathology ; physiopathology ; Kidney Diseases ; blood ; drug therapy ; physiopathology ; urine ; Kidney Function Tests ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Organ Size ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; metabolism ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Triglycerides ; blood