Experiment Resarch Of Protective Mechanism Of Polyaspartic Acid On Ototoxicity Of Gentamycin In Guinea Pig

This study was composed of three parts:First partObjective:To observe the effect of polyaspartic acid(PAA) on gentamicindisturbing phospholipid metabolism in cochlear of guinea pig and investigate the protective mechanism of polyaspartic acid on gentamicin -ototoxicity. Methods: utilizing high performance liquid chromatography (HPLC) to determinate quantitatively phospholipid in cochlear tissue, in same time recording ABR and using transmission electron microscope to observe ultrastructural change of lysosome in the cochlear hair cells at different using drug time and in different using drug groups. Results: â‘ After using drug 1-day, there was not significant difference in determination of phospholipid among four groups (P>0.05); there was also not significant difference in ABR thresholds and ultrastructural change of lysosome in the cochlear hair cells among four groups. â‘¡After using 5-days, there was significant difference in determination of phosphatidylinositol (P1) and phosphatdylinositol phosphate (PIP) among four groups (P<0.01); there was increase tending in ABR thresholds in group-I; and ultrastructural change of lysosome in the cochlear hair cells of group-I showed increase of number and expansion of volume. â‘¢After using 10-days, there was only significant difference in determination of phosphatdylinositol phosphate (PIP) among four groups (P<0.01), while there was not significant difference in determination of other phospolipides among four groups (P>0.05); there was significant difference in ABR thresholds (P<0.01); ABR thresholds of group-I had significant increasing; Ultrastructural change of lysosome in the cochlear hair cells of group-I showed more signifcant change in number and volume than that after using drug 5-days. Conclusion: PAA has significant inhibiting effect on gentamicin-disturbing phospholipid matabilism in cochlear of guinea pig, which shows that PAA has protective effect on gentamicin-ototoxicity and phospholipdosis in the cochlear hair cells in guinea pig.Second partObjective:To observe the effect of polyaspartic acid(PAA) on gentamicin-inhibiting inositidelipid messenger system in cochlear of guinea pig and investigate the protective mechanism of polyaspartic acid on gentamicin -ototoxicity. Methods: By using incorporation of [3H]-inositol and high performance liquid chromatography (HPLC) technique to determine inositol phosphates (IPs) radioactivity-i the level of polyphosphatidylinositol(PPI) and the activity of PPI phospholipase C(PPI PLC) in cochlear tissue at different using drug time and in different using drug groups Results: @After using drug 1-day, there was not change in il's radioactivity, the level of polyphosphatidylinositol (PPI) and the activity of PPI phospholipase C(PPI PLC) among four groups (P>0.05). ~After using drug 5-days, there was a increase in the level of polyphosphatidylinositol(PPI) and a decrease of IPs radioativity, the activity of PPJ phospholipase C(PPI PLC) was decrease by using only GM; but, compared with control groups there was not change in LPs radioativity, the level of polyphosphatidylinositol(PPI) and the activity of PPI phospholipase C(PPI PLC) by using PAA and GM. ?After using drug 10-days, there were increase in the level of polyphosphatidylinositol(PPL) and IPs radioactivity , the activity of PPI phospholipase C(PPI PLC) was some increase by using only GM; but, compared with using only GM 5-days, there was not change of the level of polyphosphatidylinositol(PPJ);.Whereas there was not change in li's radioativity, the level of polyphosphatidylinositol(PPJ) and the activity of PPI phospholipase C(PPJ PLC) by using PAA and GM. Conclusion: PAA has some preventing effects on gentamicin-inhibiting inositidelipid messenger system in cochlear of guinea pig, which shows that PAA has protective effect on gentamicin-ototoxicity in guinea pig.Third part Objective:To observe that polyaspartic acid(PAA) inhibits gentamicininduced reactive oxygen species (ROS) generation in cochlear of guinea pig and...