flunarizine and Acute-Kidney-Injury

This study was aimed to evaluate the protective effect of flunarizine on cisplatin-induced acute renal failure. Administration of cisplatin (6 mg/kg, i.p. on day 6) significantly increased serum blood urea nitrogen and creatinine, urinary N-acetyl β-D-glucosaminidase, tissue thiobarbituric acid reactive substances and total calcium whereas, decreased body weight, fractional excretion of sodium, creatinine clearance tissue-reduced glutathione, mitochondrial cytochrome c oxidase, and ATP levels were observed in acute renal failure rats. Moreover, cisplatin produced histopathological changes in the renal tissue. Furthermore, flunarizine (100, 200, and 300 μM/kg, p.o., for six consecutive days) was administered to evaluate its therapeutic potential in acute renal failure, and the results were compared with cyclosporin A (50 μM/kg, p.o., for six consecutive days) as a reference drug. Flunarizine resulted in the attenuation of cisplatin-induced renal dysfunction, oxidative stress marker, mitochondrial damage, and histopathological changes in rats. 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 cisplatin via mitochondrial permeability transition pore inactivation potential.

Topics: Acetylglucosaminidase; Acute Kidney Injury; Adenosine Triphosphate; Animals; Blood Urea Nitrogen; Body Weight; Calcium; Cisplatin; Creatinine; Cyclosporine; Electron Transport Complex IV; Female; Flunarizine; Glutathione; Kidney; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Rats; Rats, Sprague-Dawley; Sodium; Thiobarbituric Acid Reactive Substances

A case of flunarizine hydrochloride (FZ)-induced severe urinary retention and meteorism which resulted from sphincter spasm of the urinary bladder and the anus is presented. An 81-year-old female had received 10 mg/day FZ orally for 12 months before hypokinesia and general fatigue developed. Physical examination revealed slight rigidity of the extremities, abdominal distention and spasm of the anal sphincter muscle. Laboratory examinations showed uremia (BUN 88 mg/dl, Creatinine 16.8 mg/dl) and abdominal X-ray demonstrated marked distention of the small and large bowels. Renal failure improved within 2 days after massive urination using a urethral catheter. Abdominal distention was improved by the ileus and anal tubes. The difficulties of urination and defecation and decreased mobility of the extremities were resolved one month after the cessation of FZ. No organic changes were detected in urinary, intestinal and neurological systems by cystoscopy, CT, MRI and gastrointestinal fiberscopy. Serum concentration of FZ was 42.5 ng/ml on admission but decreased slowly to 17.9 ng/ml 80 days later. Serum half life was calculated to be 55 days which was 3 times longer than that healthy younger volunteers.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Female; Flunarizine; Gases; Humans; Intestinal Obstruction; Intestines; Urinary Retention

The effects of three chemically dissimilar calcium-blocking drugs were studied in experimental post-ischaemic renal failure, in the rat. After 45 min unilateral clamping and contralateral nephrectomy, post-ischaemic verapamil administration protected renal function (p less than 0.025), but flunarizine, either before or after ischaemia, was not beneficial. Following 60 min bilateral renal pedicle clamping, nifedipine administration was not beneficial. Verapamil was the only calcium-blocking drug which attenuated the post-ischaemic renal dysfunction. Calcium blockers which differ in their modes of action, differ in their ability to protect the kidney from ischaemia.

Topics: Acute Kidney Injury; Animals; Calcium Channel Blockers; Flunarizine; Ischemia; Kidney; Male; Nifedipine; Rats; Rats, Inbred Strains; Verapamil