The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: mechanisms of otoprotection.
D-methionine (D-met) protects against cisplatin (CDDP) ototoxicity, but the mechanisms are not well understood. This study investigated D-met protection of cochlear oxidative state as measured by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and malondiadehyde (MDA) levels. The design comprised four groups of five rats each: (1) a saline control group, (2) a CDDP-only-treated group, (3) a CDDP group pretreated with D-met, and (4) a group receiving only D-met. Auditory brainstem response testing (ABR) was performed before and 3 days after injection. CDDP alone caused marked hearing loss; significantly reduced SOD, CAT, and GR levels; and increased MDA levels, but D-met pretreatment protected against these changes. These studies suggest that D-met protects cochlear antioxidant enzyme levels from CDDP-induced decrements. The excellent correlation of enzyme levels with hearing loss and weight loss suggests that antioxidant enzyme level protection may underlie, at least in part, D-met's otoprotective action.
Campbell
Kathleen C M
KC
Southern Illinois University School of Medicine, Springfield, IL, USA. kcampbell@SIUmed.edu
Meech
Robert P
RP
Rybak
Leonard P
LP
Hughes
Larry F
LF
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D034381:Hearing Loss / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007273:Injections, Intramuscular; D015227:Lipid Peroxidation / Q000187:drug effects; D008715:Methionine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats
D000970:Antineoplastic Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D008715:Methionine; D002945:Cisplatin