Effect of Furosemide and Spironolactone on urinary zinc excretion in rats

Background: Zinc deficiency is associated with numerous diseases including hypertension, diabetes, obesity, immune dysregulation, cancer, depression and congenital anomalies. There are many reasons of zinc deficiency including some medications. If zinc supplementation is used with these medicines than many diseases can be prevented. Subjects and methods: This experimental study was planned to observe the effect of single diuretic dose of furosemide and spironolactone on zinc urinary excretion and blood levels in normal rats. Eighteen adult healthy male Sprague Dawley rats were randomly divided into three groups. After saline load rats were given distilled water, furosemide (10 mg/kg) and spironolactone (20 mg/kg) as single oral dose. Blood and urine samples were collected after five hours and analysed for zinc concentration by flame atomic absorption spectrophotometer. Results: Single oral dose of furosemide and spironolactone highly significantly increased urinary zinc excretion (p-value <0.001 vs normal control), and increased blood zinc level (p-value <0.001 vs. normal control). Value of both variables were significantly higher in furosemide-treated group (p-value <0.001 vs. furosemide-treated). Conclusion: Results of this research conclude that furosemide and spironolactone increase urinary zinc excretion when used for short period. It is also postulated that blood zinc concentration is not reliable measure to assess the zinc status of the body because its level shows compensatory rise during deficiency states.

Renal handling of zinc in chronic kidney disease patients and the role of circulating zinc levels in renal function decline

Background Zinc deficiency is commonly encountered in chronic kidney disease (CKD). The aims of this study were to assess whether zinc deficiency was related to increased renal excretion of zinc and to the progression of CKD. Methods Plasma and 24-h urinary zinc levels, urinary electrolytes and uromodulin were measured in 108 CKD patients and 81 individuals without CKD. Serum creatinine values were collected for 3 years to calculate the yearly change in estimated glomerular filtration rate (eGFR). Multivariable regression analysis was performed to assess the association between baseline zinc levels and yearly change in eGFR. Results CKD patients had lower circulating zinc levels and higher 24-h urinary zinc excretion than non-CKD participants (612.4 ± 425.9 versus 479.2 ± 293.0 µg/day; P = 0.02). Fractional excretion (FE) of zinc was higher and it significantly increased at more advanced CKD stages. Zinc FE was correlated negatively with 24-h urinary uromodulin excretion (r=−0.29; P &lt; 0.01). Lower baseline plasma zinc levels were associated with a faster yearly decline of renal function in age, gender, diabetes and hypertension adjusted models, but this relationship was no longer significant when baseline eGFR or proteinuria were included. Conclusions Zinc levels are lower in CKD, and not compensated by reduced renal zinc excretion. The inverse association between urinary zinc excretion and uromodulin possibly points to an impaired tubular activity, which could partly account for zinc imbalance in CKD. These data suggest that zinc status is associated with renal function decline, but further studies elucidating the underlying mechanisms and the potential role of zinc supplements in CKD are needed.

Effects of endotoxin on zinc metabolism in human volunteers

After stress or trauma, the serum zinc concentration decreases. This study evaluated possible mechanisms for hypozincemia with the use of a human endotoxemia model. Two doses of endotoxin [lipopolysaccharide (LPS)] were administered on consecutive mornings to 12 healthy volunteers, and each subject was also studied after saline injection. Blood was analyzed for zinc, cytokines (tumor necrosis factor-alpha and interleukin-6), albumin, albumin-zinc binding, and C-reactive protein (CRP). Serial 24-h urine collections were analyzed for zinc. Each LPS dose briefly increased plasma cytokine concentrations and decreased the serum zinc concentration. Serum albumin, the major zinc binding protein, did not decrease, but a progressive increase in CRP was found. LPS did not alter zinc binding affinity to serum albumin. Urine zinc losses were not increased. We conclude that hypozincemia in this model cannot be explained by decreased serum albumin, changes in serum albumin-zinc binding, or increased urinary zinc excretion. Because hypozincemia was transient and followed cytokine peaks, we postulate that LPS-stimulated hypozincemia is mediated, at least partly, by a cytokine-directed internal redistribution of zinc.