Pharmacokinetic Study Of Antioxidants Lipoic Acid In Guinea Pig Inner Ear And Its Inhibitory Effects On Apoptosis After Acute Acoustic Trauma

Objective①Compare of intravenous and intratympanic administration, apply high-performance liquid chromatography (HPLC)to study the pharmacokinetics of lipoic acid in guinea pig perilymph and to provide experimental evidence for clinical delivery methods and dose;②To investigate the effect of lipoic acid in the guinea pig cochlear'auditory-related apoptosis on acute acoustic trauma(110 dB SPL 5 h) after two injection routes. Methods①The concentration of lipoic acid in perilymph was detected respectively by HPLC after administration;②make use of TUNEL to mark the apoptotic cells and observe the characteristics of apoptosis by Ordinary light microscope and confocal microscope,and two kinds of auditory function in guinea pigs after injection methods were compared.Results①The maximum of concentration of lipoic acid administrated via intratympanic was 171.7μg/ml, and via intravenous was 33.7μg/ml; the MRT of intratympanic injection was 3.7 h while intravennous injection was 2.9 h; the half life(t1/2) of the former was 1.8 h but the latter was 2.1 h;②The ABR threshold of guinea pigs remained at a high level after noise exposure. Confocal microscopy and light microscopy observation of apoptosis in the results are basically consistent. However, there was no significant difference on apoptosis inhibition between the two injection routes.Conclusions①The drug concentration can both be detected via intravenous and intratympanic injection in perilymph of guinea pig, But the effect of local administration via intratympanic is obvious superior to systemic administration;②Noise exposure of 110 dB SPL 5 h can lead to acute acoustic trauma and induce a variety apoptosis of guinea pig hearing-related cells;③Lipoic acid has a good protective effect on apoptosis after noise exposure. Injection through tympanic and intravenous both have an significant inhibitory effect on apoptosis after noise exposure. But compared with intravenous injection,tympanic injection has no obvious advantage.