Parathyroidectomy has a beneficial effect on experimental cisplatin nephrotoxicity.
It has recently been suggested that selective parathyroidectomy modifies drug-induced acute renal failure. In the present study, we tested whether parathyroid hormone (PTH) could play a role in the pathogenesis of cisplatin (CP) nephrotoxicity. Parathyroidectomized rats (PTX) with normal blood calcium, were injected with two different doses of CP (group Ia: 10 mg/kg and group Ib: 6 mg/kg) and their renal functions were evaluated after 72 hours (group 1 a) and 120 h (group 1 b), respectively. All animals exhibited a milder course of acute renal failure when compared to sham-PTX CP treated rats, with lower serum creatinines (SCr) (group Ia: 1.99 +/- 0.14 vs 2.91 +/- 0.56 mg/dl, p less than 0.05) (group Ib: 1.45 +/- 0.08 vs 1.80 +/- 0.09 mg/dl, p less than 0.05) and blood urea (BUN) (group Ia: 76 +/- 5 vs 115 +/- 19 mg/dl, p less than 0.05) (group Ib: 70 +/- 9 vs 88 +/- 10 mg/dl p less than 0.05). Furthermore, the i.p. administration of PTH (50 I.U. twice daily for 9 days) to normal rats treated with CP (6 mg/kg) aggravated the CP-induced ARF as compared to vehicle injected animals (SCr 2.23 +/- 0.16 vs 1.63 +/- 0.19 mg/dl, p less than 0.05 and BUN 153 +/- 22 vs 97 +/- 20 mg/dl, p less than 0.05). Treatment with the calcium channel blocker verapamil (4 mg/kg) nine days before and three days after CP (4 mg/kg) administration, had no significant effect on cisplatin nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Capasso
G
G
Department of Pediatrics, University of Naples, Italy.
Giordano
D R
DR
de Tommaso
G
G
De Santo
N G
NG
Massry
S G
SG
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D001806:Blood Urea Nitrogen; D002118:Calcium / Q000097:blood; D002945:Cisplatin / Q000633:toxicity*; D008297:Male; D009399:Nephrons / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D014700:Verapamil; D002945:Cisplatin; D002118:Calcium