Zinc-dependent and independent actions of hydroxyhydroquinone on rat thymic lymphocytes.

Coffee contains hydroxyhydroquinone (HHQ). HHQ is one of the by-products released during bean roasting. Therefore, it is important to elucidate the bioactivity of HHQ to predict its beneficial or adverse effects on humans. We studied zinc-dependent and independent actions of commercially procured synthetic HHQ in rat thymocytes using flow cytometric techniques with propidium iodide, FluoZin-3-AM, 5-chloromethylfluorescein diacetate, and annexin V-FITC. HHQ at 1050 µM elevated intracellular Zn levels by releasing intracellular Zn. HHQ at 10 µM increased cellular thiol content in a zinc-dependent manner. However, HHQ at 30-50 µM reduced cellular thiol content. Although the latter actions of HHQ (30-50 µM) were suggested to increase cell vulnerability to oxidative stress, HHQ at 0.3-100 µM significantly protected cells against oxidative stress induced by HO. The process of cell death induced by HO was delayed by HHQ, although both HO and HHQ increased the population of annexin V-positive living cells. However, HHQ at 10-30 µM promoted cell death induced by A23187, a calcium ionophore. HHQ at 10-30 µM exerted contrasting effects on cell death caused by oxidative stress and Ca overload. Because HHQ is considered to possess diverse cellular actions, coffee with reduced amount of HHQ may be preferable to avoid potential adverse effects.