1. The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.
- Author
-
Macan M, Konjevoda P, Lovric J, Koprivanac M, Kelava M, Vrkic N, and Bradamante V
- Subjects
- Animals, Aryldialkylphosphatase blood, Gemfibrozil metabolism, Gemfibrozil toxicity, Heart drug effects, Heart physiology, Hydrogen Peroxide metabolism, Hypolipidemic Agents metabolism, Hypolipidemic Agents toxicity, Kidney drug effects, Kidney enzymology, Lipid Peroxidation drug effects, Lipid Peroxides metabolism, Liver drug effects, Liver enzymology, Liver metabolism, Male, Peroxisomes drug effects, Rats, Rats, Inbred F344, Rats, Wistar, Aryldialkylphosphatase metabolism, Gemfibrozil pharmacology, Hypolipidemic Agents pharmacology, Malondialdehyde metabolism
- Abstract
There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis., (© 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.)
- Published
- 2011
- Full Text
- View/download PDF