Profile of minocycline neuroprotection in bilirubin-induced auditory system dysfunction.
Excessive hyperbilirubinemia in human neonates can cause permanent dysfunction of the auditory system, as assessed with brainstem auditory evoked potentials (BAEPs). Jaundiced Gunn rat pups (jjs) exhibit similar BAEP abnormalities as hyperbilirubinemic neonates. Sulfadimethoxine (sulfa) administration to jjs, which displaces bilirubin from serum albumin into tissues including brain, exacerbates acute toxicity. Minocycline administered prior to sulfa in jjs protects against BAEP abnormalities. This study evaluates the neuroprotective capabilities of minocycline HCl (50 mg/kg) administered 30 or 120 min after sulfa (200 mg/kg) in 16 days old jjs. BAEPs are recorded at 6 or 24 h post-sulfa. Abnormal BAEP waves exhibit increased latency and decreased amplitude. The sulfa/saline treated jjs exhibited a significantly increased interwave interval between waves I and II (I-II IWI) and significantly decreased amplitudes of waves II and III compared to the saline/saline jjs. The minocycline 30 min post-sulfa (sulfa/mino+30) group was not significantly different from the saline/saline control group, indicating neuroprotection. The minocycline 120 min post-sulfa (sulfa/mino+120) group had a significantly decreased amplitude of wave III at both 6 and 24h. These studies indicate that minocycline has a graded neuroprotective effect when administered after acute bilirubin neurotoxicity.
Department of Neurology, Box 980599, Virginia Commonwealth University, Richmond, VA 23298-0599, USA. acrice@vcu.edu
Ann C
AC
Rice
Victoria L
VL
Chiou
Sarah B
SB
Zuckoff
Steven M
SM
Shapiro
D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000378:metabolism / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D006311:Hearing Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006932:Hyperbilirubinemia / Q000139:chemically induced; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011911:Rats, Gunn; D013412:Sulfadimethoxine / Q000009:adverse effects; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D013412:Sulfadimethoxine; D008911:Minocycline; D001663:Bilirubin