Malays. Appl. Biol. (June
IN VITRO TOXICITY OF MICONAZOLE ON RAT HEPATOCYTES: INVOLVEMENT OF CYTOCHROME P450
*SOMCHIT, M.N. and NOR-SHAHIDA, A.R.
Toxicology Unit, Department of Biomedical Sciences,
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
ABSTRACT
This present study investigated the in vitro cytotoxicity of miconazole on rat hepatocytes pretreated with phenobarbital. In vitro incubation of hepatocytes with miconazole revealed a time- and dose-dependent cytotoxicity, which was observed by lactate dehydrogenase leakage. However this cytotoxicity was not severe even at the highest dose of miconazole (1.0 mM). Phenobarbital, which is a cytochrome P 450 inducer produced significantly higher content of cytochrome P 450 in treated hepatocytes when compared to non-treated hepatocytes. Phenobarbital pretreatment resulted in significant protection of the hepatocytes against miconazole-induced toxicity in vitro. Phenobarbital treated hepatocytes had a significantly higher cell viability when compared to non-treated hepatocytes. Phenobarbital played a role in the cytoprotection of hepatocytes against miconazole in vitro. Therefore, cytochrome P450 may be involved in the detoxification of miconazole.
ABSTRAK
Kajian ini adalah untuk mengenalpasti ketoksikan ke atas sel hepar tikus yang diaruh oleh dadah anti-kulat mikonazole secara in vitro. Pengeraman in vitro sel hepar dengan mikonazole menunjukkan kesan sitotoksisiti mengikut masa dan dos dimana ianya diukur dengan kaedah enzim laktat dehidrogenase. Ketoksikan yang diaruh oleh mikonazole adalah tidak teruk, walaupun pada dos tertinggi (1.0 mM). Pra-rawatan tikus dengan penobarbital, iaitu bahan kimia yang merangsang sitokrom P450 melindungi sel hepar tikus dari kesan toksisiti mikonazole in vitro. Sel hepar yang di pra-rawat dengan penobarbital mempunyai jumlah sel hidup yang lebih tinggi secara statistik jika dibandingkan dengan sel hepar yang tidak di pra-rawat. Penobarbital memainkan peranan di dalam melindungi sel-sel hepar dari toksisiti mikonazole secara in vitro. Oleh kerana itu, sitokrom P450 berperanan di dalam pennyahtoksikan mikonazole.
Key words: Cytotoxicity, miconazole, hepatocytes, rats.
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