High Cholesterol Feeding May Induce Tubular Dysfunction Resulting in Hypomagnesemia

Abstract

Background/Aims: Hypomagnesemia may induce hypercholesterolemia, but the contrary has not been described yet. Thus, magnesium homeostasis was evaluated in rats fed a cholesterol-enriched diet for 8 days. This study has a relevant clinical application if hypomagnesemia, due to hypercholesterolemia, is confirmed in patients with long-term hypercholesterolemia. Methods: Both hypercholesterolemic (HC) and normocholesterolemic rats (NC) were divided into sets of experiments to measure hemodynamic parameters, physiological data, maximum capacity to dilute urine (C_H_₂_O), variations (Δ) in [Ca²⁺]_i and the expression of transporter proteins. Results: HC developed hypomagnesemia and showed high magnesuria in the absence of hemodynamic abnormalities. However, the urinary sodium excretion and C_H_₂_O in HC was similar to NC. On the other hand, the responses to angiotensin II by measuring Δ [Ca²⁺]_i were higher in the thick ascending limb of Henle’s loop (TAL) of HC than NC. Moreover, high expression of the cotransporter NKCC2 was found in renal outer medulla fractions of HC. Taken together, the hypothesis of impairment in TAL was excluded. Actually, the expression of the epithelial Mg²⁺ channel in renal cortical membrane fractions was reduced in HC. Conclusion: Impairment in distal convoluted tubule induced by hypercholesterolemia explains high magnesuria and hypomagnesemia observed in HC.

Rosiglitazone Did Not Induce Acute Kidney Injury in Normocholesterolemic Rats Despite Reduction in Glomerular Filtration Rate

“…We did not choose Zucker rats to perform the experiments as changes in plasma lipid profiles are associated with obesity, glucose intolerance, hypertension and renal sodium retention in these animals [31]. Hence, we induced hypercholesterolemia by feeding the rats with a high cholesterol diet for 8 days since the animals become hypercholesterolemic with similar body weight, AP and GFR of their control as we have previously reported [15,16]. …”

“…We fed the animals with a standard diet (normocholesterolemic rats - NC) or a standard diet supplemented with 4% (w/w) cholesterol and 1% (w/w) cholic acid (hypercholesterolemic rats - HC) [15,16]. Both NC and HC were treated or not with rosiglitazone maleate (Avandia, GlaxoSmithKline, GSK) at a level of 48 mg/kg diet for eight days.…”

Prevenção da nefrotoxicidade da anfotericina B por meio do uso de fitomedicamentos

“…The fractional excretion of sodium (FENa) was calculated using the formula: FENa=urinary sodium x serum creatinine/serum sodium x urinary creatinine x 100 (11) . Fractional excretion of potassium: the potassium values in urine and blood were determined by means of the ion-selective electrode method, using the Architect® CI8200 (Abbot) biochemical analyser.…”

“…Fractional excretion of potassium: the potassium values in urine and blood were determined by means of the ion-selective electrode method, using the Architect® CI8200 (Abbot) biochemical analyser. The fractional ex- cretion of potassium (FEK) was calculated using the formula: FEK=urinary potassium x serum creatinine/serum potassium x urinary creatinine x 100 (11) . Fractional excretion of magnesium: the magnesium values in urine and blood were determined by means of the ion-selective electrode method, using the Architect® CI8200 (Abbot) biochemical analyser.…”

“…Fractional excretion of magnesium: the magnesium values in urine and blood were determined by means of the ion-selective electrode method, using the Architect® CI8200 (Abbot) biochemical analyser. The fractional excretion of magnesium (FEMg) was calculated using the formula: FEMg=urinary magnesium x serum creatinine/serum magnesium x urinary creatinine x 100 (11) . Urinary peroxides: these were measured using the FOX-2 method, with ferrous xylenol orange which oxidizes with the ion Fe 2+ and produces a complex that is blue/purple in color (α=4,3 x 10 4 M -1 cm -1 ) (12) .…”