Drug induced alterations in some rat hepatic microsomal components: a comparative study of four structurally different antimalarials.
Alterations in microsomal drug metabolizing enzymes, microsomal lipids and some serum enzymes following pre-treatment of rats with therapeutic doses of four structurally different antimalarial compounds, chloroquine (CQ), quinine (Q), quinacrine (QK) and primaquine (PQ) have been investigated. CQ and Q significantly decreased the activities of aminopyrene N-demethylase, aniline hydroxylase and both microsomal and cytosolic glutathione S-transferases. Only aniline hydroxylase was markedly decreased by QK, while PQ did not have much effect on any of these enzymes. CQ, Q and QK significantly increased the cholesterol:phospholipid ratio while all four compounds decreased the phosphatidyl choline:sphingomyelin (PC/S) ratio. All the drugs increased the activities of the serum enzymes glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase and alkaline phosphatase. The possible relationships of these results to structural variations in the four drugs being investigated has been discussed.
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D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000815:Aniline Hydroxylase / Q000378:metabolism*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002738:Chloroquine / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011319:Primaquine / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000962:Antimalarials; D010743:Phospholipids; D002738:Chloroquine; D002784:Cholesterol; D011803:Quinine; D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase; D005982:Glutathione Transferase; D011796:Quinacrine; D011319:Primaquine