N-acetylcysteine attenuates noise-induced permanent hearing loss in diabetic rats.
The purpose of this study is to investigate whether repeated noise exposure aggravates the level of permanent noise-induced hearing loss (NIHL) in diabetic rats and whether N-acetylcysteine (NAC), a precursor of glutathione, attenuates the level of noise-induced permanent hearing loss in diabetic rats. Fifty male Wistar rats were divided into four groups: 12 non-diabetic control rats with saline injection (Control-Saline), 11 non-diabetic control rats with NAC injection (Control-NAC), 13 streptozotocin-induced diabetic rats with saline injection (Diabetes-Saline) and 14 streptozotocin-induced diabetic rats with NAC injection (Diabetes-NAC). NAC (325mg/kg) was given by intraperitoneal injection twice per day (b.i.d.) for 14 days starting 2 days before noise exposure. All rats were exposed to noise for 8hours per day for 10 consecutive days to develop noise-induced permanent hearing loss. The hearing status of all animals was evaluated with auditory brainstem responses (ABR) evoked by clicks and tone bursts. ABRs were measured before and at 1hour, 1 week, 2 weeks and 4 weeks after noise exposure. After a recovery time of 4 weeks, animals were decapitated, and the loss of hair cells was assessed microscopically. In all groups, ABR thresholds failed to return to pre-exposure values throughout the experimental period. The ABR threshold to clicks was markedly elevated in the Diabetes-Saline group (36.9+/-2.3dB SPL), less elevated in the Control-Saline and Diabetes-NAC groups and least in the Control-NAC group (19.5+/-2.0dB SPL) at 4 weeks after noise exposure. Diabetes caused increased susceptibility to noise-induced hearing loss, and NAC treatment reduced the loss in both control and diabetic rats. Cochleograms revealed no gross destruction of hair cells in the non-diabetic groups or the Diabetes-NAC group; however, a significant number of outer hair cells (OHCs) were lost in the Diabetes-Saline group. This study demonstrated that diabetics were prone to developing more severe NIHL than non-diabetics and that NAC could preserve most OHCs and attenuate the permanent noise-induced hearing loss in both groups.
Wu
Hung-Pin
HP
Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan.
Hsu
Chuan-Jen
CJ
Cheng
Tsun-Jen
TJ
Guo
Yueliang Leon
YL
D000111:Acetylcysteine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D001786:Blood Glucose; D013311:Streptozocin; D005978:Glutathione; D000111:Acetylcysteine