Cr(VI)-containing compounds are known carcinogens that are present in industrial settings and in the environment. The biological mechanisms responsible for the initiation and pregression of diseases resulting from exposure to Cr(VI) are not fully understood. In the last two decades, there has been increasing evidence of the correlation between Cr(VI)-induced generation of reactive oxygen species and carcinogenic actions. This article summarizes the current literature on Cr(VI)-induced generation in various chemical and biological systems. This article also covers the relationship between Cr(VI)-induced oxidative stress and activation of transcription factors NF-kappaB, AP-1, p53, and hypoxia-inducible factor 1, regulation of cell cycle, and induction of apoptosis.

Emodin, a major active anthraquinone, frequently interacts with other drugs. As changes of efflux transporters on intestine are one of the essential reasons why the drugs interact with each other, a validated Ussing chamber technique was established to detect the interactions between emodin and efflux transporters, including P-glycoprotein (P-gp), multidrug-resistant associated protein 2 (MRP2), and multidrug-resistant associated protein 3 (MRP3). Digoxin, pravastatin, and teniposide were selected as the test substrates of P-gp, MRP2, and MRP3. Verapamil, MK571, and benzbromarone were their special inhibitors. The results showed that verapamil, MK571, and benzbromarone could increase digoxin, pravastatin, and teniposide absorption, and decrease their Er values, respectively. Verapamil (220 μM) could significantly increase emodin absorption at 9.25 μM. In the presence of MK571 (186 μM), the Papp values of emodin from M-S were significantly increased and the efflux ratio decreased. With the treatment of emodin (185, 370, and 740 μM), digoxin absorption was significantly decreased while teniposide increased. These results indicated that emodin might be the substrate of P-gp and MRP2. Besides, it might be a P-gp inducer and MRP3 inhibitor on enterocyte, which are reported for the first time. These results will be helpful to explain the drug–drug interaction mechanisms between emodin and other drugs and provide basic data for clinical combination therapy.

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