Disturbance of regulation of sodium by cis-diamminedichloroplatinum in perilymph of the guinea pig cochlea.
We studied the acute effects of cis-diamminedichloroplatinum (CDDP) on the cochlear partition and inner ear fluid in the guinea pig. At 48 hours after the administration of a single intramuscular injection of CDDP, 12.5 mg/kg of body weight, the endocochlear resting potential (EP) was significantly decreased to 32.1 +/- 1.8 mV in the treated animals, versus 80.6 +/- 1.0 mV in the control animals. There was a significant rise in potassium (K+), sodium (Na+), and chlorine (Cl-) in the endolymph of the animals treated with CDDP as compared with the control animals. Only Na+ was found to increase significantly in the perilymph, reaching more than twice the level of the control animals; both K+ and Cl- remained within the normal range. Serum electrolytes also remained within the normal range. Evaluation of modified ionic permeabilities across the endolymph-perilymph barrier showed an apparent increase in Na+ permeability and a normal range of K+ and Cl- permeabilities. Histopathologic examination of the cochlea showed a moderate collapse of the endolymphatic space, with atrophy of the stria vascularis and destruction of the outer hair cells. The findings suggest that the acute changes produced in the cochlea by administration of CDDP were attributable to a breakdown in the regulation of Na+ metabolism in the perilymph.
Department of Otorhinolaryngology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
S
S
Komune
K
K
Matsuda
T
T
Nakagawa
T
T
Kimitsuki
K
K
Hisashi
A
A
Inokuchi
S
S
Komiyama
T
T
Kobayashi
D000818:Animals; D002713:Chlorine / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D004711:Endolymphatic Duct / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000473:pathology; D006706:Homeostasis; D007273:Injections, Intramuscular; D008297:Male; D008564:Membrane Potentials; D010498:Perilymph / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010539:Permeability; D011188:Potassium / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D012964:Sodium / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D013316:Stria Vascularis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D013997:Time Factors
D002713:Chlorine; D012964:Sodium; D002945:Cisplatin; D011188:Potassium