Treatment of Human Porphyria’s with Glucose and Antioxidants is Now Best Understood

Porphyrinogenic drug 2‐allyl‐2‐isopropylacetamide (AIA) increases the destruction of liver heme, particularly cytochrome P‐450 [2], whereas porphyrinogenic drug 3,5‐diethoxycarbonyl‐1,4‐ dihydrocollidine (DDC) is a potent depletor of hepatic heme due to its combined property of destroying heme and inhibiting heme synthesis [3]. AIA/DDC treatment results in acute deficiency of heme, marked de‐repression of ALA‐S and, consequently, exacerbated production of ALA and other heme precursors in the liver [4]. This combined treatment has been reported to induce an experimental porphyria resembling quite accurately acute variegate porphyria in rats [4]. Accumulated ALA has been associated with iron‐mediated oxidative damage to biomolecules and cell structures [5] through reactive oxygen species (ROS) generation [6]. ROS are able to oxidize nucleic acids, proteins, lipids, or carbohydrates, inactivating key cellular functions [7]. It has been demonstrated that AIA/DDC treatment promotes an oxidative environment with ROS increases [4] (Figure 1).