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J.Health Sci., 55(4), 560-566, 2009

p-Hydroxybenzoate Esters Enhance Mouse Contact Hypersensitivity

Fumitoshi Sakazaki,a Hitoshi Ueno,a Hisamitsu Nagase,b and Katsuhiko Nakamuro*, a

aDepartment of Public Health & Preventive Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotogecho, Hirakata, Osaka 573-0101, Japan and bDepartment of Hygienics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan

p-Hydroxybenzoate esters (parabens), which are often used in cosmetics as preservatives, have been reported to have estrogenic and anti-androgenic effects and to cause contact dermatitis. In this paper, we evaluate the effects of parabens on contact hypersensitivity, an allergic response to low molecular weight chemicals that causes contact dermatitis. Female BALB/c mice were administered 1200 mg/kg of butylparaben and sensitized by painting 3% 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (OXA) on their backs. Seven days later, the mice were challenged by painting 1% OXA on the ear and the ear thickness was measured. Ear auricles were excised and the RNA expressions of interleukin (IL)-18 and interferon (IFN)-γ were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Butylparaben enhanced ear swelling at 6 hr after the elicitation of allergy. Butylparaben at a dosage of 600 mg/kg was sufficient to aggravate contact hypersensitivity. Among the six parabens examined, butylparaben exerted the strongest allergy-enhancing activity. Butylparaben also enhanced the RNA expression of IL-18 before the challenge with OXA and the RNA expression of IFN-γ at 6 hr after the challenge. These results suggest that parabens could enhance IL-18 and IFN-γ expression and exacerbate mouse contact hypersensitivity to OXA.