[Protective effect of peperphentonamine injection through the otocyst against gentamicin- induced cochlear damage in guinea pigs].
OBJECTIVE
To explore the relationship of gentamicin-induced cochlear damage with autophagy-related protein LC3, beclin1, Na(+-)K(+-)2Cl(-) cotransporter (NKCC1) mRNA and endothelin-1 (ET-1), and investigate the protective mechanism of PPTA against gentamicin-induced cochlear damage.


METHODS
Sixty guinea pigs were randomly divided into control group (with saline and artificial perilymph injections), model group (with gentamicin and artificial perilymph injections), concurrent treatment group (with gentamicin and PPTA injections), model control group (with artificial perilymph injection 7 days after gentamicin injection) and delayed treatment group (with PPTA injection 7 days after gentamicin injection). Saline and gentamicin (160 mg/kg) were injected intraperitoneally, and artificial perilymph and PPTA were injected into the otocysts on a daily basis for 7 consecutive days. Hearing impairment of the guinea pigs was analyzed with ABR, and the protein expressions of beclin1 and LC3 in cochlear tissue were tested. The expression of NKCC1 mRNA was detected with RT-PCR, and the expression of ET-1 was detected immunohistochemically.


RESULTS
The ABR thresholds in the model group and model control group were similar (P>0.05) , but significantly higher than those in the other 3 groups (P<0.05); the threshold was significantly lower in concurrent treatment group than in delayed treatment group (P<0.05). Compared with those in the other 4 groups, the expressions of LC3 II, beclin1, and NKCC1 mRNA were significantly increased in the model group (P<0.05); and those in delayed treatment group were significantly lower than those in the model control group (P<0.05). The expressions of ET-1 in the Corti organ, striavascularis and spiral ganglion were significantly higher in the model group but significantly lower in the control group than those in the other 4 groups; ET-1 expression was significantly lower in delayed treatment group than in the model control group.


CONCLUSIONS
PPTA offers protection against gantamicin-induced cochlear damage in guinea pigs by inhibiting cell autophagy and suppressing of NKCC1 and ET-1 expressions. Early intervention with PPTA produces better therapeutic effect, suggesting that gantamicin causes irreversible injury of the auditory cells.
Department of Otalaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. E-mail: popli0808@163.com.
Bo-Bo
BB
Li
Jian
J
Wu
Jing
J
Chen
Hao
H
Chen
Yong-He
YH
Li
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000071186:Beclin-1; D003051:Cochlea / Q000187:drug effects*; D019332:Endothelin-1 / Q000378:metabolism; D005839:Gentamicins / Q000009:adverse effects*; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism
D015104:3,4-Methylenedioxyamphetamine; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D019332:Endothelin-1; D005839:Gentamicins; D008869:Microtubule-Associated Proteins; D064506:Solute Carrier Family 12, Member 2; C580809:5-((3,4-methylenedioxyphenylethane)methylamino)-1-p-hydroxyphenyl-1-penten-3-one; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C578879:Slc12a2 protein, rat