title: The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.
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.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Macan
authors.forename: Macan
authors.initials: M
authors.lastname: Marija
authors.forename: Paško
authors.initials: P
authors.lastname: Konjevoda
authors.forename: Konjevoda
authors.initials: K
authors.lastname: Paško
authors.forename: Jasna
authors.initials: J
authors.lastname: Lovric
authors.forename: Lovrić
authors.initials: L
authors.lastname: Jasna
authors.forename: Marijan
authors.initials: M
authors.lastname: Koprivanac
authors.forename: Koprivanac
authors.initials: K
authors.lastname: Marijan
authors.forename: Marta
authors.initials: M
authors.lastname: Kelava
authors.forename: Kelava
authors.initials: K
authors.lastname: Marta
authors.forename: Nada
authors.initials: N
authors.lastname: Vrkic
authors.forename: Vrkić
authors.initials: V
authors.lastname: Nada
authors.forename: Vlasta
authors.initials: V
authors.lastname: Bradamante
authors.forename: Bradamante
authors.initials: B
authors.lastname: Vlasta
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000097:blood / Q000378:metabolism*; D015248:Gemfibrozil / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D020675:Peroxisomes / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar
chemical_list: D000960:Hypolipidemic Agents; D008054:Lipid Peroxides; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D043303:Aryldialkylphosphatase; D015248:Gemfibrozil