[Experimental observation of antagonism of polyaspartic acid against gentamicin-induced phospholipidosis in cochlea of guinea pig].
OBJECTIVE
To observe the effect of polyaspartic acid (PAA) on gentamicin-induced disturbance of phospholipid metabolism in cochlea of Guinea pig.


METHODS
Ninety-four Guinea pigs were divided into 4 groups administered with PAA, PAA + GM, GM, or normal saline respectively. Auditory brain-stem response (ABR) was recorded before and one, five and ten days after the experiment. High performance liquid chromatography (HPLC) was used to determinate the amount of phospholipid in cochlear tissue, and ultrastructural change of lysosomes in the cochlear hair cells was observed by transmission electron microscopy one, five, and ten days after the experiment.


RESULTS
No difference in any indicator was found one day after the beginning of experiment in all groups. The amounts of phosphatidylinositol (PI) and phosphatidylinositol-phosphate (PIP) increased significantly five days after administration of GM (19.7 micrograms +/- 6.6 micrograms and 121 micrograms +/- 21 micrograms respectively). The amount of PIP increased significantly 10 days after administration of GM (126 micrograms +/- 8 micrograms). Transmission electron microscopy showed an increase of number and volume of lysosome in cochlear outer hair cells and appearance of Hensen's body five days after administration of GM. Such changes became more significant and some lysosomes broke in the 10th day. The ABR threshold began to increase 5 days after the administration of GM, and continued to increase with time.


CONCLUSIONS
PAA has inhibitory effect on gentamicin-induced lysosomal phospholipidosis in cochlea of Guinea pig, thus inhibiting gentamicin-induce hearing loss.
Guo
Y
Y
General Hospital of PLA, Beijing 100853, China.
Jiang
S
S
Yang
W
W
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003051:Cochlea / Q000378:metabolism; D015834:Cochlear Diseases / Q000139:chemically induced / Q000188:drug therapy*; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D008064:Lipidoses / Q000188:drug therapy*; D008297:Male; D010743:Phospholipids / Q000378:metabolism*
D005839:Gentamicins; D010743:Phospholipids; D001224:Aspartic Acid