PMID: 9185043Jun 1, 1997Paper

Acetaminophen cytotoxicity in mouse eye: mitochondria in anterior tissues are the primary target

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
C ZhaoH Shichi

Abstract

Acetaminophen (APAP) injected into C57BL/6 mice (cytochrome P450 inducer-responsive strain) that had been pretreated with b-naphthoflavone (BNF) produced ocular tissue damage, including cataract. Our previous histocytochemical studies showed that tissue damage spread in association with the flow of the aqueous humor and appeared first in the ciliary epithelium, followed by the iris and corneal endothelium and, finally, the lens. The neural retina, retinal pigmented epithelium and choroid remained unaffected. A close examination of the affected tissues indicated that mitochondria are the primary target of APAP cytotoxicity. In order to investigate whether the respiratory capacity of mitochondria is more sensitive to APAP cytotoxicity than mitochondrial morphology, we determined in this work the oxygen uptake by eye tissues dissected from BNF-pretreated and APAP-injected C57BL/6 mice. Oxygen uptake by the ciliary body/iris decreased about 60% at 90 min and 85% at 120 min after APAP administration. The oxygen uptake was inhibited about 50% by 10 microM rotenone. Since the earliest sign of mitochondrial damage was noted at 120 min, the result indicates that mitochondrial energy dysfunction precedes morphological alterations. It was...Continue Reading

References

Apr 7, 1992·Biochimica Et Biophysica Acta·M A SciamannaC P Lee
Jun 1, 1989·Archives of Biochemistry and Biophysics·J L RaucyM Black
Jan 1, 1986·Journal of Ocular Pharmacology·P B KoneruR T Koda
May 1, 1988·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·B M LubekP G Wells
Mar 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·D C DahlinS D Nelson
Apr 22, 1993·Biochemical Pharmacology·K E ThummelJ T Slattery

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Citations

Jul 9, 2002·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Larissa P MartynkinaHitoshi Shichi
Nov 7, 2003·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Priya MathurHitoshi Shichi
Dec 28, 1999·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·W QianH Shichi
Sep 8, 2000·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·W Qian, H Shichi
Jun 4, 2004·Expert Opinion on Investigational Drugs·Hitoshi Shichi

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