Abstract: Objective To evaluate the role of L-carnitine(LCAR)supplementation in hearing threshold and cochlear damage in newborn guinea pigs exposed to gentamicin in utero.Methods Pregnant albino guinea pigs were intraperitoneally injected with 100 mg/kg body weight gentamicin once a day for 7 consecutive days,or gentamicin and LCAR at gestational day 51 to 57.At postnatal day 14,the pups were examined in the distortion product otoacoustic emission(DPOAE)task.The temporal bones were immunohistochemically stained for caspase-3,using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling(TUNEL)method.Results Gentamicin used during pregnancy decreased the DPOAE threshold shifts at different frequencies of 1,2,4,5,and 8 kHz(8.38±2.28,12.56±3.22,10.46±1.98,12.22±1.72,and 17.73±2.16 dB,respectively).In contrast,LCAR supplementation,coincidentally with gentamicin exposure,ameliorated these changes(14.26±1.47,20.98±2.39,19.23±2.15,22.56±1.41,and 29.13±3.14 dB,respectively).In addition,gentamicin used during pregnancy increased the percentage of apoptotic cells in hair cells(34.6%),but LCAR supplementation decreased the percentage of apoptotic cells(15.7%,P<0.05).Conclusion Our data offer a conceptual framework for designing clinical trials using a safe nutrient,LCAR,as a simple preventive strategy for gentamicin-induced ototoxicity.