Effectiveness of tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy for hepatoprotection and diuresis in a rat cirrhotic model
نویسندگان
چکیده
Spironolactone and furosemide, which are used to treat ascites associated with decompensated cirrhosis, are ineffective in treating refractory ascites. Hence, combination therapy with tolvaptan, a vasopressin V2 receptor antagonist, has been approved in Japan. Tolvaptan monotherapy and combination therapy with furosemide inhibit fibrosis in cardiac remodeling; hence, we examined these therapies in a rat cirrhotic model, including their usefulness in inhibiting hepatic fibrosis. In the present study, we used a model of hepatic fibrosis induced by a choline-deficient l-amino-acid-defined diet + diethylnitrosamine. Rats were divided into a low-dose furosemide group (15 mg/kg/day), a high-dose furosemide group (100 mg/kg/day), a tolvaptan monotherapy group (10 mg/kg/day), a low-dose furosemide/tolvaptan combination therapy group, and a control group which received neither furosemide nor tolvaptan; we then assessed diuretic effects and hepatic fibrosis. The tolvaptan monotherapy group and the furosemide/tolvaptan combination therapy group demonstrated significantly higher urine volume than the control group and the low-dose furosemide group. In addition, tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy were found to inhibit hepatic fibrosis and yield a hepatoprotective effect by an antioxidative mechanism. The results of the present study suggest that tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy are highly effective for hepatoprotection and diuresis.
منابع مشابه
Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure.
Diuretics are frequently required to treat fluid retention in patients with congestive heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohumoral activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V2 receptor, and its levels are increased in CHF. This study was designed to assess the effects of a single...
متن کاملEfficacy of combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients: A randomized study
AIM To assess the effects of a combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients. METHODS A two-center, randomized, open-label, prospective study was conducted. Japanese patients who met the criteria were randomized to trial group and the combination diuretic group (received 7.5 mg of tolvaptan) or the conventional diuretic group (received 40 mg of furosem...
متن کاملInnovative Methodology Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure
Costello-Boerrigter, Lisa C., William B. Smith, Guido Boerrigter, John Ouyang, Christopher A. Zimmer, Cesare Orlandi, and John C. Burnett, Jr. Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol 290: F273–F278, 2006. First published September 27, 2005; doi:10.1152/aj...
متن کاملTriple Diuretics and Aquaretic Strategy for Acute Decompensated Heart Failure due to Volume Overload
Diuretics, including furosemide, metolazone, and spironolactone, have historically been the mainstay of therapy for acute decompensated heart failure patients. The addition of an aquaretic-like vasopressin antagonist may enhance diuresis further. However, clinical experience with this quadruple combination is lacking in the acute setting. We present two hospitalized patients with acute decompen...
متن کاملCombined aquaretic and diuretic therapy in acute heart failure
INTRODUCTION Acute heart failure (AHF) is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time. METHODS AND RESULTS A protocol of combined therapy with furosemide, metolazone, and spirono...
متن کامل