Drugs to cure avian influenza infection – multiple ways to prevent cell death

Yuan, S

Simply providing humans with 50 mg/kg/body weight of VC in one or few doses (oral or other) on a fixed schedule will not replicate the sufficiency seen in normal mammals. Mice and birds can synthesize considerable amounts of VC, 16,17 but they can be still infected by avian influenza. Therefore, additional treatments other than ROS scavengers have been applied. For the avian-influenza-infected patient with pneumonia, continuous increase of alveolar/capillary membrane permeability is the most common damage. 12 Mitochondria have a critical role in mediating calcium overload and oxidative damage (e.g., hydrogen peroxide)-induced cell death, such as ischemia reperfusion (IR) injury. [18] [19] [20] The mitochondrial permeability transition (mPT) after this injury leads to mitochondrial swelling, outer membrane rupture and the release of apoptotic mediators (such as cytochrome c). 18 The mPT pore is thought to consist of the adenine nucleotide translocator, a voltage-dependent anion channel and cyclophilin D. Cyclosporin A (CsA) can effectively inhibit cyclophilin D and, therefore, it protects myocardial cells form IR injury (such as myocardial infarction). 18 H1N1 infection inactivated the cellular catalase, thus leading to the accumulation of ROS (mainly hydrogen peroxide), 21 whereas H5N1 induced extracellular calcium influx, leading to apoptosis. 22 ROS accumulation, extracellular calcium influx and the accompanying mitochondrial damages were also found in hypoxemia patient's lung cells. 23 Thus, ROS accumulation (especially hydrogen peroxide) and calcium influx may be the common injury factors for both IR injuries and ARDS damages. CsA may have a protective effect on such damages caused by the avian influenza infection.