Effect of Orally Ebselen (SPI-1005) towards Glutathione and Malondialdehyde Blood Level and Otoacoustic Emissions Result in Soldiers with Acoustic Trauma Risk

Abstract

Excessive noise exposure can cause acoustic trauma by causing mechanical and metabolic (oxidative) stress to the inner ear structure (cochlea) (TA). Apoptosis and necrosis of cochlear hair cells are caused by oxidative stress, which is caused by a rise in free radical ROS/RNS in the organs of Corti. Oxidative stress was characterized by increasing of malondialdehyde (MDA), decreasing of glutathione peroxidase (GPx) enzyme, and abnormal otoacoustic emission value (refer). Defense mechanism toward oxidative stress was mediated by endogenous antioxidant enyzme (superoxide dismutase/SOD, catalase/CAT, and GPx). Cellular mechanism of glutation peroxidase mimetic was similar as GPx. Aim of this study was to determine the impact of glutathione peroxidase mimetic to glutathione peroxidase and malondialdehyde level in blood, also otoacoustic emission value on soldiers with risk of TA due to explosion of Howitzer 105 artillery weapon. The design of this study was clinical trial pre and post design, randomized, double blind and placebo controlled, on 34 new recruit soldiers in Artillery Academy of Indonesian Army, during the soldiers were trained to firing Howitzer 105 artillery weapon, from 7th-10th July 2014 in Cimahi and Batujajar. Subjects were divided into 2 groups, the exposure group (group given treatment) and control group. Exposure group was given glutathione peroxidase mimetic (Ebselen SPI 1005) 200mg, orally once daily during the training, meanwhile control group was given. Malondialdehyde and Glutathione Peroxidase level in blood, pure tone audiometry and otoacoustic emission value (DPOAEs) was measured from those two groups, before and after firing training. The data was analyzed using parametric and non parametric, with Number Needed to Treat (NNT, 95%CI) and significance value (p<0.05). The results of this study showed the number of acoustic trauma events in controle group based on pure tone audiometry test was 23.5%, exposure group was 0%, and based on DPOAEs test the controle group showed 47.1% abnormal/refer, exposure group showed 100% normally/pass, and this difference stastically significance (p<0.051). The group which was given Ebselen SPI 1005 showed increasing 82.4% erythrocyte GPx level (NNT, 95%CI=1.889 [1.1593.016]; p=0.004), showed increasing 88.2% plasma GPx level (NNT, 95%CI=1.417 [0.970-1.775]; p<0.001), decreasing 100% erythrocyte MDA level (NNT, 95%CI = 2.125 [1.335-3.987]; p=0.01), showed decreasing 94.1% plasma MDA level (NNT, 95%CI=2.125 [1.29-3.904]; p=0.01), and resulting 100% in normal/pass DPOAEs value (NNT, 95%CI = 2.125 [1.335-3.987]; p=0.01). Giving Ebselen SPI 1005 to soldiers at risk of acoustic trauma during the firing of a Howitzer 105 artillery weapon increased GPx levels in the blood, decreased MDA levels in the blood, and resulted in DPOAEs values that were regular (pass).