PMID: 9657284Jul 10, 1998Paper

Elucidation of mitochondrial effects by tetrahydroaminoacridine (tacrine) in rat, dog, monkey and human hepatic parenchymal cells

Archives of Toxicology
D G RobertsonF A de la Iglesia

Abstract

Tetrahydroaminoacridine (tacrine) causes morphological and functional changes in the endoplasmic reticulum, ribosomes, and mitochondria in the liver of humans and animals. In order to investigate species differences as well as to understand the morphological changes, we examined the effects of tacrine on respiration and electron transport in mitochondria isolated from rat, dog, monkey, and human liver. Tacrine produced significantly decreased respiratory control ratios (RCR) in all species at concentrations ranging from 5 to 25 microg/ml. Human mitochondria were more sensitive to tacrine effects with RCR decreased 24% at 5 microg/ml while other species were unaffected at this concentration. The tacrine effects were characterized by increased hepatic mitochondrial State 4 respiration in rats and decreased State 3 respiration in humans. Mitochondria from aged rats were more sensitive to the effects of tacrine than mitochondria from young animals, with significantly decreased RCR at 10 microg/ml in aged rats while mitochondria from young rats were unaffected at this concentration. Concomitant with the respiratory changes, mitochondrial DNA synthesis was impaired. Since tacrine undergoes extensive biotransformation, we also explore...Continue Reading

Citations

Dec 10, 1999·British Journal of Pharmacology·D Lagadic-GossmannA Guillouzo
Oct 31, 2001·Alimentary Pharmacology & Therapeutics·M JacobR J Simpson
Mar 26, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Chunpeng GaoJun Cao
Nov 19, 2013·The Journal of Pharmacy and Pharmacology·Katharina ZengerBirgit Kraus
Feb 25, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Chunpeng GaoJun Cao
Sep 17, 2003·The Journal of Toxicological Sciences·Urs A Boelsterli
Aug 27, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Abdellah MansouriAlain Berson
Apr 3, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Jana JanockovaMaria Kozurkova
Jul 20, 2010·Journal of Biomolecular Screening·Kenneth A GiulianoPatricia A Johnston
Nov 2, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bernard Fromenty

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