title: The protective effect of Salvia miltiorrhiza on gentamicin-induced ototoxicity.
abstract: OBJECTIVE
  The clinical use of aminoglycoside antibiotics is limited in most countries because of auditory toxicity side effects. However, their use is common in developing countries because they are inexpensive and convenient. Salvia miltiorrhiza extracts are used clinically in China for their antioxidant properties. We investigated the effect of a clinically approved injectable S. miltiorrhiza solution on inducible nitric oxide synthase (iNOS) generation induced by the aminoglycoside antibiotic gentamicin and an ototoxicity protective mechanism.
  
  
  METHODS
  Sixty adult guinea pigs were used in this study and divided into four groups. Auditory brainstem response (ABR) testing was performed before and after treatments and animals were sacrificed for morphological and immunostaining assays after determining threshold shifts in ABR. The cochleae were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to observe ultrastructural changes. In addition, hair cell loss, iNOS and caspase-3 expression, and apoptosis were measured.
  
  
  RESULTS
  The result showed that hearing loss, iNOS overexpression accompanied with disorganization in the cochlea, and terminal deoxynucleotidyl transferase- mediated dUTP- biotin nick end labeling (TUNEL)-stained positive cells in animals treated with gentamicin. However, pretreatment with S. miltiorrhiza (3g/kg/day for 10 days) decreased gentamicin-induced hearing loss, attenuated iNOS and caspase-3 expression, and decreased the number of apoptotic cells. Furthermore, it also reduced the ultrastructural damage due to ototoxicity as observed by SEM and TEM.
  
  
  CONCLUSIONS
  These findings indicate that S. miltiorrhiza protects against gentamicin-induced ototoxicity and could apply to the protection of ototoxicity.
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, China. Electronic address: lijuanshi6@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis; D003051:Cochlea / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects*; D034381:Hearing Loss / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations / Q000008:administration & dosage / Q000627:therapeutic use*; D027561:Salvia miltiorrhiza; D016896:Treatment Outcome
chemical_list: D005839:Gentamicins; D028321:Plant Preparations; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3