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Abstract Short-lived reactive nitrogen species and reactive oxygen species have acquired significant attention in the field of biomedical science. Nitric oxide (NO), which was thought to be an unstable gas and pollutant, is now regarded as a gas transmitter like H2S and CO. NO is synthesized inside the mammalian body by l-arginine via three different isoforms of NO synthase whereas pyruvate is a glycolysis product and substrate for TCA cycle. Due to poor solubility and stability, therapeutic potential of pyruvate is limited. Ethyl pyruvate (EP) is now considered as a suitable replacement of pyruvate. In this paper, we will try to focus the effect of NO and EP in Schwann cell dedifferentiation, proliferation, nerve degeneration, and regeneration during Wallerian degeneration (WD) of peripheral nerve injury along with their neuroprotective effects, cardiovascular functioning, support in hepatic complication, etc.