Exposure of U937 cells to peroxynitrite promotes mitochondrial superoxide formation via a mechanism dependent on both inhibition of complex III and increased mitochondrial Ca²⁺ accumulation. Otherwise inactive concentrations of the oxidant produced the same maximal effects in the presence of either complex III inhibitors or agents mobilizing Ca²⁺ from the ryanodine receptor and enforcing its mitochondrial accumulation. l-Ascorbic acid (AA) produced similar enhancing effects in terms of superoxide formation, DNA strand scission and cytotoxicity. However, AA failed to enhance the intra-mitochondrial concentration of Ca²⁺ and the effects observed in cells supplemented with peroxinitrite, while insensitive to manipulations preventing the mobilization of Ca²⁺, or the mitochondrial accumulation of the cation, were also detected in human monocytes and macrophages, which do not express the ryanodine receptor. In all these cell types, mitochondrial permeability transition-dependent toxicity was detected in cells exposed to AA/peroxynitrite and, based on the above criteria, these responses also appeared Ca²⁺-independent. The enhancing effects of AA are therefore similar to those mediated by bona fide complex III inhibitors, although the vitamin failed to directly inhibit complex III, and in fact enhanced its sensitivity to the inhibitory effects of peroxynitrite.

Vitamin K is a fat-soluble vitamin essential for the activation of vitamin K-dependent proteins involved in coagulation and other physiological processes. Neonates are particularly vulnerable to vitamin K deficiency due to limited placental transfer, low hepatic stores, immature liver function, and insufficient dietary intake, especially in exclusively breastfed infants. This review summarizes the biochemistry and pharmacokinetics of vitamin K, focusing on their role in the pathogenesis of late vitamin K deficiency bleeding (VKDB), including intracranial hemorrhage in early infancy. The limitations of conventional coagulation tests are discussed, highlighting the importance of functional biomarkers such as PIVKA-II (Proteins Induced by Vitamin K Absence or Antagonist-II) for the early detection of subclinical deficiency. Despite effective prophylaxis at birth, late VKDB cases still occur, likely due to declining vitamin K levels over time and nutritional factors. These findings underscore the need for prolonged vitamin K supplementation following adequate prophylaxis at birth, particularly to protect high-risk newborns from late VKDB. Strategies may include vitamin K-containing multivitamin supplementation in preterm infants, as well as daily oral vitamin K supplementation (150 µg/day) in exclusively breastfed infants, in order to ensure adequate vitamin K status during early infancy.