Influence of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors on mitochondrial respiration in rat liver during ischemia

Effects of 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmacology 1994-08, Vol.270 (4), p.365-369
Main Authors: Satoh, Kumi, Nakai, Tohru, Ichihara, Kazuo
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - metabolism
Animals
Biological and medical sciences
Cell Fractionation
Drug toxicity and drugs side effects treatment
Glutamic Acid - metabolism
HMG-CoA (3-hydroxy-3-methylglutaryl conenzyme A) reductase inhibitor
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Ischemia
Ischemia - metabolism
Liver - blood supply
Liver - drug effects
Liver - enzymology
Liver mitochondria
Lovastatin - analogs & derivatives
Lovastatin - pharmacology
Male
Medical sciences
Mitochondria, Liver - drug effects
Mitochondria, Liver - enzymology
Oxygen Consumption - drug effects
Pharmacology. Drug treatments
Pravastatin - pharmacology
Rats
Rats, Sprague-Dawley
Simvastatin
Succinates - metabolism
Toxicity: digestive system
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Effects of 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Liver ischemia was induced by cessation of the systemic circulation for 60 min. Liver mitochondria were isolated and the respiration was determined by polarography using glutamate and succinate as substrates. In the vehicle-treated group, ischemia decreased QO 3, respiratory control index (RCI; QO 3/QO 4), and ADP/O ratio. Pretreatments with pravastatin and simvastatin enhanced the decreases in QO 3 measured with either glutamate or succinate, and in ADP/O ratio measured with succinate. Because of decreasing QO 4, HMG-CoA reductase inhibitors did not modify the changes in RCI due to ischemia. There were no significant differences in respiratory indices between pravastatin- and simvastatin-treated groups. In conclusion, HMG-CoA reductase inhibitors may enhance respiratory impairment of liver mitchondria under pathophysiological conditions, such as ischemia.
ISSN:0926-6917
0014-2999
DOI:10.1016/0926-6917(94)90014-0