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Pretreatment with 1,8-cineole potentiates thioacetamide-lnduced hepatotoxicity and immunosuppression

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Abstract

The effect of 1,8-cineole on cytochrome P450 (CYP) expression was investigated in male Sprague Dawley rats and female BALB/c mice. When rats were treated orally with 200, 400 and 800 mg/kg of 1,8-cineole for 3 consecutive days, the liver microsomal activities of benzy-loxyresorufin-and pentoxyresorufin-O-dealkylases and erythromycinN-demethylase were dose-dependently induced. The Western immunoblotting analyses clearly indicated the induction of CYP 2B1/2 and CYP 3A1/2 proteins by 1,8-cineole. At the doses employed, 1,8-cineole did not cause toxicity, including hepatotoxicity. Subsequently, 1,8-cineole was applied to study the role of metabolic activation in thioacetamide-induced hepatotoxicity and/or immunotoxicity in animal models. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 50 and 100 mg/kg of thioacetamide in saline. 24 h later, thioacetamide-induced hepatotoxicity was significantly potentiated by the pretreatment with 1,8-cineole. When female BALB/c mice were pretreated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 100 mg/kg of thioacetamide, the antibody response to sheep red blood cells was significantly potentiated. In addition, the liver microsomal activities of CYP 2B enzymes were significantly induced by 1,8-cineole as in rats. Taken together, our results indicated that 1,8-cineole might be a useful CYP modulator in investigating the possible role of metabolic activation in chemical-induced hepatotoxicity and immunotoxicity.

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Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, 712-749, Kyungsan, Korea

    Nam Hee Kim, Sun Hee Hyun, Chun Hua Jin, Sang Kyu Lee, Dong Wook Lee, Tae Won Jeon, Eung Seok Lee & Tae Cheon Jeong

  2. College of Natural Resources, Yeungnam University, 712-749, Kyungsan, Korea

    Jae Sung Lee

  3. College of Pharmacy, Chungang University, 156-756, Seoul, Korea

    Young Jin Chun

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  1. Nam Hee Kim
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  2. Sun Hee Hyun
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Correspondence to Tae Cheon Jeong.

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Kim, N.H., Hyun, S.H., Jin, C.H. et al. Pretreatment with 1,8-cineole potentiates thioacetamide-lnduced hepatotoxicity and immunosuppression. Arch Pharm Res 27, 781–789 (2004). https://doi.org/10.1007/BF02980149

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