Jie Wang1, Ye Wang2, Xin Chen2, Peng-zhi Zhang2, Ze-tao Shi2, Li-ting Wen2, Jian-hua Qiu2, Fu-quan Chen3. 1. Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China; Department of Otolaryngology-Head and Neck Surgery, Xi'an Children's Hospital, Shanxi, Xi'an, China. 2. Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China. 3. Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle Western Road, Xi'an, China. Electronic address: chenfq2@yahoo.com.
Abstract
OBJECTIVE: Although histone deacetylase (HDAC) inhibition has been shown to protect against gentamicin (GM)-induced hearing loss in vitro, its protective effect has not been proven in vivo. In the present study, the aim was to investigate the protective effect of sodium butyrate (NaB), a specific HDAC inhibitor, on GM-induced ototoxicity in vivo. METHODS: Forty 8-week-old albino guinea pigs were divided into two experimental groups. Group 1 (n=10) underwent bilateral ear surgery to place sponges (0.3mm(3)) permeated with NaB (10μl, 100mg/ml) and physiological saline (10μl; control) in the right and left round window niches, respectively. The sponges were left in place for 15days to evaluate the effects of NaB at the applied concentration. Group 2 (n=30) underwent the same bilateral ear surgery described for Group 1, except three days after surgery, the animals received intramuscular GM injections (200mg/kg/day) for 5 consecutive days. Seven days after the final GM injection, the protective effects of NaB were examined. RESULTS: After 15days of NaB treatment (10μl, 100mg/ml), an increase in histone acetylation was detected in Corti organ samples. Auditory brainstem response (ABR) threshold shifts and hair cell loss were also reduced in NaB-treated ears after GM administration. Furthermore, GM treatment increased HDAC1 expression in outer hair cells (OHCs) in vivo, and NaB blocked this action. CONCLUSION: GM increases HDAC1 expression in OHCs, and NaB is able to block this action. Thus, it appears that the HDAC inhibitor, NaB, attenuates GM-induced hearing loss in guinea pigs.
OBJECTIVE: Although histone deacetylase (HDAC) inhibition has been shown to protect against gentamicin (GM)-induced hearing loss in vitro, its protective effect has not been proven in vivo. In the present study, the aim was to investigate the protective effect of sodium butyrate (NaB), a specific HDAC inhibitor, on GM-induced ototoxicity in vivo. METHODS: Forty 8-week-old albino guinea pigs were divided into two experimental groups. Group 1 (n=10) underwent bilateral ear surgery to place sponges (0.3mm(3)) permeated with NaB (10μl, 100mg/ml) and physiological saline (10μl; control) in the right and left round window niches, respectively. The sponges were left in place for 15days to evaluate the effects of NaB at the applied concentration. Group 2 (n=30) underwent the same bilateral ear surgery described for Group 1, except three days after surgery, the animals received intramuscular GM injections (200mg/kg/day) for 5 consecutive days. Seven days after the final GM injection, the protective effects of NaB were examined. RESULTS: After 15days of NaB treatment (10μl, 100mg/ml), an increase in histone acetylation was detected in Corti organ samples. Auditory brainstem response (ABR) threshold shifts and hair cell loss were also reduced in NaB-treated ears after GM administration. Furthermore, GM treatment increased HDAC1 expression in outer hair cells (OHCs) in vivo, and NaB blocked this action. CONCLUSION:GM increases HDAC1 expression in OHCs, and NaB is able to block this action. Thus, it appears that the HDAC inhibitor, NaB, attenuates GM-induced hearing loss in guinea pigs.
Authors: Rahul Mittal; Nicole Bencie; George Liu; Nicolas Eshraghi; Eric Nisenbaum; Susan H Blanton; Denise Yan; Jeenu Mittal; Christine T Dinh; Juan I Young; Feng Gong; Xue Zhong Liu Journal: Gene Date: 2020-07-29 Impact factor: 3.688
Authors: Béatrice Milon; Sunayana Mitra; Yang Song; Zachary Margulies; Ryan Casserly; Virginia Drake; Jessica A Mong; Didier A Depireux; Ronna Hertzano Journal: Biol Sex Differ Date: 2018-03-12 Impact factor: 5.027