Inhibition of NADH oxidation by chloramphenicol in the freely moving rat measured by picosecond time-resolved emission spectroscopy.
Owing to the lack of methods capable to monitor the energetic processes taking place within small brain regions (i.e. nucleus raphe dorsalis, nRD), the neurotoxicity of various categories of substances, including antibiotics and psycho-active drugs, still remains difficult to evaluate. Using an in vivo picosecond optical spectroscopy imaging method, we report that chloramphenicol (CAP), besides its well-known ability to inhibit the mitochondria protein synthesis, also influences the NADH/NAD+ redox processes of the respiratory chain. At a 200-mg/kg dose, CAP indeed produces a marked increase in the fluorescent signal of the nRD which, according to clear evidence, is likely to be related to the NADH concentration. This effect also implies an efficient inhibition of complex I of the respiratory chain by CAP. It refers to the mechanism through which the adverse effects of the antibiotic may take place. It could explain why paradoxical sleep, a state needing aerobic energy to occur, is suppressed after CAP administration. The present approach constitutes the first attempt to determine by fluorescence methods the effects of substances on deep brain structures of the freely moving animal. It points out that in vivo ultrafast optical methods are innovative and adequate tools for combined neurochemical and behavioural approaches.
Mottin
Stéphane
S
LTSI, CNRS UMR 5516, University of St-Etienne, F-42023 St-Etienne Cedex 02, France. MOTTIN@univ-st-etienne.fr
Laporte
Pierre
P
Cespuglio
Raymond
R
D000818:Animals; D001463:Barbiturates / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D002701:Chloramphenicol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D042967:Electron Transport Complex I; D005336:Fiber Optic Technology; D007834:Lasers; D008297:Male; D009243:NAD / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
D001463:Barbiturates; D011500:Protein Synthesis Inhibitors; D009243:NAD; D002701:Chloramphenicol; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I