Wounds are internal or external bodily injuries or lesions caused by mechanical, chemical, viral, bacterial or thermal means, which disrupt the normal continuity of structures. Such bodily injuries include contusions, which are wounds in which the skin is unbroken, incisions, i.e., wounds in which the skin is broken by a cutting instrument, and lacerations, which are wounds in which the skin is broken by a dull or blunt instrument.
Wound healing consists of a series of processes whereby injured tissues are repaired, specialized tissue is generated, and new tissue is reorganized. Wound healing consists of three major phases: (a) an inflammation phase (0-3 days), (b) a cellular proliferation phase (3-12 days), and (c) a remodeling phase (3-6 months).
During the inflammation phase, platelet aggregation and clotting form a matrix which traps plasma proteins and blood cells to induce the influx of various types of cells. Wounds produce oxygen radicals. Mammalian cells are continuously exposed to activated oxygen species such as superoxide (02-), hydrogen peroxide (H2O2), hydroxyl radicals (OH), peroxynitrite (ONOO-) and singlet oxygen (1O2). In vivo, these reactive oxygen intermediates are generated by cells in response to aerobic metabolism, catabolism of drugs and other xenobiotics, ultraviolet and x-ray radiation, and the respiratory burst of phagocytic cells (such as white blood cells) to kill invading bacteria and viruses introduced through wounds. The toxic by-products generated from the catabolism of drugs to treat infected and cancerous cells activate the inflammatory process generally through the activation of NF- Kappa B, which can delay healing. Hydrogen peroxide, for example, is produced during respiration of most living organisms especially by stressed and injured cells.
It is at this time that peroxynitrite is produced and causes NF- kappa B to be over expressed, thus delaying the healing process. This over expression of peroxynitrite will also destroy drugs needed to treat various diseases including infected wounds. Most wounds also produce pain, swelling, itching, ischemia, crusting, erythema, and scarring, which is caused by the over expression of NF-kappa B from the over expression of peroxynitrite and the metabolites it produces when it reacts with drugs, all of which are undesirable.
Thus, the ability of pyruvate and other alpha-keto acids to eliminate peroxynitrite in the body and to protect nitric oxide (NO) from other oxygen radicals, allows NO to deactivate NF-kappa B, which, will reduce inflammation. In wounds and in HSV-1 infected cells, sodium pyruvate along with alpha keto isovalerate eliminated peroxynitrite, thus reduced viral loads, increased the synthesis of NO and in combination with antiviral agents, eliminated the virus completely from the infected cells.