D-methionine provides excellent protection from cisplatin ototoxicity in the rat.
Cisplatin (CDDP) is a widely used chemotherapeutic agent. Unfortunately, CDDP is highly ototoxic. We tested D-methionine (D-Met), a sulfur containing compound, as an otoprotectant in male Wistar rats. Complete data sets were obtained for five groups of five animals each, including a treated control group (16 mg/kg CDDP), an untreated control group (administered an equivalent volume of saline) and three groups that received either 75, 150, or 300 mg/kg D-Met 30 min prior to the 16 mg/kg CDDP dosing. Auditory brainstem response (ABR) thresholds were obtained in response to clicks, and 1 kHz, 4 kHz, 8 kHz, and 14 kHz toneburst stimuli, before and 3 days after drug administration. Scanning electron microscopy (SEM) was used to examine the outer hair cells of the apical, middle and basal turns of the cochlea. Animal weight was measured on the first and final day. D-Met provided excellent otoprotection even at the lowest level with complete otoprotection obtained for the 300 mg/kg dosing as measured by both ABR and SEM. D-Met also markedly reduced weight loss and mortality. All animals receiving D-Met (15/15) survived to the end of the study period as opposed to only 5/10 of the treated controls.
Campbell
K C
KC
Department of Surgery, SIU School of Medicine, Springfield, IL 62794-1618, USA.
Rybak
L P
LP
Meech
R P
RP
Hughes
L
L
D000161:Acoustic Stimulation; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects* / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008855:Microscopy, Electron, Scanning; D011041:Poisoning / Q000401:mortality / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D016707:Tissue Fixation; D015431:Weight Loss / Q000187:drug effects
D000970:Antineoplastic Agents; D008715:Methionine; D002945:Cisplatin