ABSTRACT
Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.
Subject(s)
Animals , Ear, Inner/growth & development , Embryo, Nonmammalian/drug effects , Gene Expression Regulation, Developmental/drug effects , Hair Cells, Auditory/metabolism , Lateral Line System/growth & development , Locomotion/drug effects , Ototoxicity/physiopathology , Toluene/toxicity , ZebrafishABSTRACT
Background Endophthalmitis is a serious infectious eye disease.Efficient drug therapy plays a key role in the early stage.There have been few researches on teicoplanin treating endophthalmitis and pharmacokinetics in ocular tissue.Objective The present study was to investigate the intraocular pharmacokinetic course and feature of intravitreal administration of teicoplanin.Methods Thirty-three Japanese white rabbits were included in this study and randomized into 6 groups.The right eyes of the rabbits were used in experiment.5 g/L of teicoplanin was injected into the vitreous cavity,and vitreous and aqueous humor samples were extracted after 15 minutes,30 minutes,1,2,4,6,12,24,48,96 and 192 hours,and the concentration of teicoplanin was determined by bioassay.Results The logarithmic value of the concentration of teicoplanin was raised with the increase in the bacterial inhibition zone diameters,of which the equation of the regression curve was Y =0.174X-0.813(R2=0.999).A good linear relationship was presented within 1.0-80.0 mg/L.Single intravitreal injection of teicoplanin was compliant with the two-compartment model.Moreover,the distribution phase Tα1/2 and elimination phase Tβ1/2 of vitreous were 1.68 and 152.15 hours,separately.And Tα1/2 and Tβ1/2 of the aqueous humor were 2.83 hours and 70.56 hours,individually.The peak teicoplanin concentrations in the vitreous and aqueous humor were(358.47±21.53)mg/L and(102.17±9.54)mg/L at 1 hour,respectively and remained at(4.38±0.68)mg/L and(2.38±0.38)mg/L,respectively 192 hours later.Conclusions Intravitreal injection of 0.5 mg of teicoplanin can remain therapeutic concentration for a long time in the vitreous and aqueous humor.