Krajka-Kuźniak Violetta, Szaefer Hanna, Baer-Dubowska Wanda
University of Medical Sciences, Department of Pharmaceutical Biochemistry, Święcickiego 4, 60-781 Poznań, Poland.
Environ Toxicol Pharmacol. 2008 Jan;25(1):27-32. doi: 10.1016/j.etap.2007.08.005. Epub 2007 Aug 24.
A simple plant phenolic acid, protocatechuic acid and a polyphenol, tannic acid are potential chemopreventive agents which inhibited the chemically induced carcinogenesis in many experimental models. We previously demonstrated that those compounds modulate the activity of xenobiotic detoxifying enzymes, including GST in mouse liver, kidney and epidermis. Intraperitoneal (i.p.) treatment with protocatechuic acid in the dose of 80mg/kg for three consecutive days increased the GST activity in liver and kidney. In case of tannic acid the same effect was observed in kidney after i.p. administration of the single dose of 80mg/kg. Topical application of phenolic acids resulted in enhancement of epidermal GST activity. The focus of this study was to further investigate the effects of these phenolic acids on the protein levels of GST isozymes in the same tissues using the treatment protocols used in our previous studies. The results confirmed the expression of GST alfa, mu, pi and theta in mouse liver, kidney and epidermis. Treatment with protocatechuic acid resulted in an increase of the expression of GST class mu in liver, but did not affect this isoform in skin and kidney. This compound inhibited the level of kidney GST pi by 35%. Tannic acid decreased the expression of GST mu, alpha and theta in liver. Application of the equimolar doses of both phenolic acids on mouse skin resulted in reduced level of the GST alpha protein. The results of our study indicate that, although moderate, the effect of protocatechuic acid and tannic acid on GST subunits in mice may play certain role in biological activity of these compounds. Of special importance could be the increased expression of GST mu in liver which is involved in detoxification of many carcinogens including polycyclic aromatic hydrocarbons.
简单的植物酚酸原儿茶酸和一种多酚——鞣酸是潜在的化学预防剂，它们在许多实验模型中均能抑制化学诱导的致癌作用。我们之前证明，这些化合物可调节外源性解毒酶的活性，包括小鼠肝脏、肾脏和表皮中的谷胱甘肽S-转移酶（GST）。连续三天腹腔注射（i.p.）80mg/kg剂量的原儿茶酸可增加肝脏和肾脏中的GST活性。对于鞣酸，单次腹腔注射80mg/kg剂量后，在肾脏中也观察到了相同的效果。酚酸的局部应用导致表皮GST活性增强。本研究的重点是使用我们之前研究中的处理方案，进一步研究这些酚酸对相同组织中GST同工酶蛋白水平的影响。结果证实了GSTα、μ、π和θ在小鼠肝脏、肾脏和表皮中的表达。用原儿茶酸处理导致肝脏中GST μ类的表达增加，但对皮肤和肾脏中的这种同工型没有影响。该化合物使肾脏GST π的水平降低了35%。鞣酸降低了肝脏中GST μ、α和θ的表达。在小鼠皮肤上应用等摩尔剂量的两种酚酸导致GST α蛋白水平降低。我们的研究结果表明，尽管程度适中，但原儿茶酸和鞣酸对小鼠GST亚基的影响可能在这些化合物的生物活性中发挥一定作用。肝脏中GST μ表达的增加可能特别重要，它参与了包括多环芳烃在内的许多致癌物的解毒过程。
