endothelin-1 and Hearing-Loss

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.. 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.. 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.. 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.

Topics: 3,4-Methylenedioxyamphetamine; Animals; Apoptosis Regulatory Proteins; Beclin-1; Cochlea; Endothelin-1; Gentamicins; Guinea Pigs; Hearing Loss; Microtubule-Associated Proteins; Solute Carrier Family 12, Member 2

To investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) in the endothelin-1 gene (EDN1) and hearing impairment in middle-aged and elderly Japanese.. Longitudinal study.. Data were collected from community-dwelling Japanese adults who participated in the Longitudinal Study of Aging biennially between 1997 and 2006. The participants at baseline were 2,231 adults aged 40 years to 79 years. An average hearing threshold level of 25 dB or better in the better ear for frequencies 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz was defined as no hearing impairment. Using generalized estimating equations to treat repeated observations within subjects, 7,097 cumulative data were analyzed to assess the association between hearing status and the EDN1 G/T polymorphism with adjustment for age, sex, histories of ear disease, occupational noise exposure, heart disease, hypertension, and body mass index under additive, dominant, and recessive genetic models.. Comparison with wild-type homozygotes (GG), heterozygotes, and mutant homozygotes (GT/TT) showed a positive association with hearing impairment after adjustment for age in model 1 (odds ratio [OR] = 1.24; 95% confidence interval [CI] = 1.02-1.50; P = .033), for age and sex in model 2 (OR = 1.29; CI = 1.06-1.57; P = .0122), and for age, sex, history of ear disease, and history of occupational noise exposure in model 3 (OR = 1.31; CI = 1.07-1.60; P = .0092). The association was also significant in model 3 under the additive model.. This study demonstrated that mutant T-allele carriers were associated with a higher risk of hearing impairment than carriers of wild-type homozygotes in middle-aged and elderly people. This result implies that endothelin-1 plays a valuable role in the cochlea.

Topics: Adult; Aged; Alleles; Asian People; Auditory Threshold; Chi-Square Distribution; Endothelin-1; Genetic Predisposition to Disease; Genotype; Hearing Loss; Humans; Longitudinal Studies; Middle Aged; Polymorphism, Genetic; Risk Factors; Surveys and Questionnaires