ABSTRACT
The effect of coadministration of fosfomycin (FOM) on nedaplatin-induced nephrotoxicity in rats was investigated for 6 days. FOM decreased nedaplatin-induced nephrotoxicity, as shown by reduced blood urea nitrogen (BUN), serum creatinine levels, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Further, there were fewer histopathological signs of nephrotoxicity in the groups treated with the combination of nedaplatin and FOM as compared with the nedaplatin-alone group. The concentration of nedaplatin was significantly lower in the renal cortex of rats treated with the combination of nedaplatin and FOM as compared with those treated with nedaplatin alone (p < 0.05). In conclusion, the concomitant administration of FOM and nedaplatin may help to achieve a chemotherapeutic strategy that reduces the nephrotoxic effects of nedaplatin.
Subject(s)
Fosfomycin/therapeutic use , Kidney Tubular Necrosis, Acute/drug therapy , Acetylglucosaminidase/urine , Animals , Blood Urea Nitrogen , Creatinine/blood , Disease Models, Animal , Fosfomycin/administration & dosage , Fosfomycin/pharmacology , Injections, Intraperitoneal , Kidney Tubular Necrosis, Acute/chemically induced , Male , Organoplatinum Compounds , Random Allocation , Rats , Rats, WistarABSTRACT
The mechanism of radiation-induced dysfunction in rat submandibular glands was investigated at the cellular level. After X irradiation (single dose, 15 Gy), a vacuolation in the acinar cells or an enlargement of the acinar lumen was observed as a typical morphological change for 2 weeks. As observed using a video-enhanced contrast differential interference contrast (VEC-DIC) microscope, exocytosis and shrinkage of the acinar cells induced by application of pilocarpine (100 microM) were markedly suppressed for 5 days and then recovered to 80% of the control levels. Using an immunohistochemical method, no significant change was observed in amylase distribution, but a marked loss of aquaporin 5 was found in the acinar cells after the irradiation. The extent and time course of pilocarpine-induced mobilization of intracellular Ca(2+) did not change after the irradiation. We conclude that radiation-induced dysfunction in the salivary glands is due to an impairment of exocytosis and a reduction of water secretion. The loss of aquaporin 5 and possibly other membrane-fusion proteins in acinar cells may be the major mechanism underlying such a dysfunction.
