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1.
Life Sci ; 289: 120192, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34871664

RESUMO

AIMS: The number of cancer survivors with cardiovascular disease is increasing. However, the effect of cancer on body fluid regulation remains to be clarified. In this study, we evaluated body osmolyte and water imbalance in rats with hepatocellular carcinoma. MAIN METHODS: Wistar rats were administered diethylnitrosamine, a carcinogenic drug, to establish liver cancer. We analyzed tissue osmolyte and water content, and their associations with aldosterone secretion. KEY FINDINGS: Hepatocellular carcinoma rats had significantly reduced body mass and the amount of total body sodium, potassium, and water. However, these rats had significantly increased relative tissue sodium, potassium, and water content per tissue dry weight. Furthermore, these changes in sodium and water balance in hepatocellular carcinoma rats were significantly associated with increased 24-h urinary aldosterone excretion. Supplementation with 0.25% salt in drinking water improved body weight reduction associated with sodium and water retention in hepatocellular carcinoma rats, which was suppressed by treatment with spironolactone, a mineralocorticoid receptor antagonist. Additionally, the urea-driven water conservation system was activated in hepatocellular carcinoma rats. SIGNIFICANCE: These findings suggest that hepatocellular carcinoma induces body mass loss in parallel with activation of the water conservation system including aldosterone secretion and urea accumulation to retain osmolyte and water. The osmolyte and water retention at the tissue level may be a causative factor for ascites and edema formation in liver failure rats.


Assuntos
Aldosterona/urina , Carcinoma Hepatocelular/urina , Dietilnitrosamina/toxicidade , Neoplasias Hepáticas Experimentais/urina , Equilíbrio Hidroeletrolítico , Redução de Peso , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Masculino , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Ratos , Ratos Endogâmicos WKY , Receptores de Mineralocorticoides/metabolismo , Espironolactona/farmacologia
2.
J Pharmacol Sci ; 147(3): 245-250, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34507633

RESUMO

Sodium/glucose cotransporter 2 (SGLT2) is a renal low-affinity high-capacity sodium/glucose cotransporter expressed in the apical membrane of the early segment of proximal tubules. SGLT2 reabsorbs filtered glucose in the kidney, and its inhibitors represent a new class of oral medications used for type 2 diabetes mellitus, which act by increasing glucose and sodium excretion in urine, thereby reducing blood glucose levels. However, clinical trials showed marked improvement of renal outcomes, even in nondiabetic kidney diseases, although the underlying mechanism of this renoprotective effect is unclear. We showed that long-term excretion of salt by the kidneys, which predisposes to osmotic diuresis and water loss, induces a systemic body response for water conservation. The energy-intensive nature of water conservation leads to a reprioritization of systemic body energy metabolism. According to current data, use of SGLT2 inhibitors may result in similar reprioritization of energy metabolism to prevent dehydration. In this review article, we discuss the beneficial effects of SGLT2 inhibition from the perspective of energy metabolism and water conservation.


Assuntos
Água Corporal/metabolismo , Metabolismo Energético/efeitos dos fármacos , Rim/metabolismo , Florizina/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/fisiologia , Administração Oral , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diurese , Glucose/metabolismo , Humanos , Hipoglicemiantes , Túbulos Renais Proximais/metabolismo , Malus/química , Osmose , Florizina/administração & dosagem , Fitoterapia , Sódio/metabolismo , Sódio/urina
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