Effects of ivermectin on the brain, liver and kidney and its interaction with P-glycoprotein inhibitor (verapamil) in rats
Ibrahim M.El-Ashmawy
Dept. of Pharmacology , Faculty of Veterinary Medicine, Alexandria University, Egypt
Abstract:
Administration of permeability-glycoprotein (Pgp) inhibitors can modify the pharmacological properties or induce toxic effects of Pgp substrates. The effects of administration of ivermectin (anthelmentic drug, Pgp substrate), either alone or simultaneously with verapamil (Pgp inhibitor) on the histological structure of the brain tissue, liver and kidney functions were investigated. Additionally, the the lipid peroxidation as malondialdehyde (MDA) and activity of the antioxidant enzymes reduced glutathione (GSH) and glutathione peroxidase (GSH peroxidase ) at these tissues were determined. The results revealed that administration of ivermectin once weekly for 4 weeks induced slight elevations of the serum transaminases ( alanine aminotransferase and aspartate aminotransferase) , alkaline phosphatase, urea and creatinine. The antioxidative defences (GSH and GSH peroxidase) at these tissues were also slightly diminished and the MDA content was slightly increased. A mild alterations on the normal histological structure of the brain, liver and kidney tissues. Meanwhile, the combined treatment of ivermectin and verapamil induced stronger harmful effects on these tissues. We concluded that ivermectin has slight toxic effects on the brain, liver and kidney tissues, but when taken with verapamil the previous effects becomes more pronounced.
