flunarizine and Kidney-Diseases

This study was aimed to evaluate the role of flunarizine on gentamicin (GEM) induced nephrotoxicity in rat. Administration of GEM (40 mg/kg, s.c. for 10 consecutive days) significantly increased blood urea nitrogen (BUN), N-acetyl β-d-glucosaminidase (NAG), thiobarbituric acid reactive substances (TBARS) and total calcium whereas, decreased body weight, fractional excretion of sodium (FrNa), creatinine clearance (CrCl), reduced glutathione (GSH), mitochondrial cytochrome c oxidase (Cyt-C oxidase) and ATP levels resulting in nephrotoxicity. Further, flunarizine (100, 200 and 300 µmol/kg, p.o.) was administered to evaluate its renoprotective effect against GEM induced nephrotoxicity and the results were compared with cylcosporin A (CsA, 50 µmol/kg, p.o.). Flunarizine resulted in the attenuation of renal dysfunction and oxidative marker changes in rats subjected to GEM induced nephrotoxicity in a dose dependent manner. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of GEM via mitochondrial permeability transition pore (MPTP) inactivation potential.

Topics: Animals; Body Weight; Cyclosporine; Flunarizine; Gentamicins; Kidney Diseases; Male; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Rats; Rats, Sprague-Dawley

We describe two twin sisters in whom calcification of different arteries was detected in the first weeks of life. Transient renal insufficiency, arterial hypertension, and skeletal abnormalities were also observed. One child had anasarca and heart decompensation at birth. Prenatal infarction of one kidney had occurred in the same infant. A kidney biopsy showed calcium deposits in all the layers of the arteries. Most findings in these patients are compatible with idiopathic arterial calcification of infancy (IACI). Investigation of calcium and phosphorus metabolism revealed spontaneously receding hypercalciuria, increased intraerythrocytic calcium levels, and transient X-ray abnormalities of the long bones. Treatment initially consisted of biphosphonate and later, the calcium antagonist flunarizin. A progressive diminution of the arterial calcification was observed in the course of both treatments.

Topics: Arterial Occlusive Diseases; Calcinosis; Calcium; Diseases in Twins; Female; Flunarizine; Humans; Hypertension, Renovascular; Infant, Newborn; Kidney; Kidney Diseases; Phosphorus

Topics: Animals; Arteriosclerosis; Blood Pressure; Coronary Artery Disease; Disease Models, Animal; Drug Evaluation, Preclinical; Flunarizine; Hypertension; Intracranial Arteriosclerosis; Kidney Diseases; Male; Rats