Ascorbyl Palmitate Augments Hypoxic Respiratory Response in the Cat

Abstract

The redox signaling is germane for the hypoxia-sensing mechanisms at the carotid body. This raises the strong possibility that agents possess reducing and antioxidant attributes, such as ascorbate, could influence the hypoxic respiratory response. However, water solubility of ascorbate makes its effectiveness at membrane-associated target sites dubious. In this study, we sought to determine the effect of ascorbyl-6-palmitate (AP), a lipid-soluble derivative of ascorbate which penetrates biomembranes, on hypoxic respiration in the anesthetized, paralyzed and ventilated cat. AP was given by gavage: 600 mg/kg daily for 6 days before the beginning of the acute experiment. Respiration was then assessed from the phrenic electroneurogram, from which peak phrenic amplitude, a surrogate of tidal component, respiratory frequency, and their product, the minute phrenic output, were quantified. The response to normocapnic hypoxia, 7% O₂ in N₂, in the AP-treated cats was compared with that in controls. We found that AP augmented hypoxic respiration, delayed the appearance of hypoxic depression and decreased it, although the stimulatory/depressant character was preserved. The results suggest that the ascorbate moiety of AP interacts with the hypoxia-sensing mechanisms. Ascorbate may affect hypoxic respiration at multiple stages of chemotransduction pathways, which are subject to continuing uncertainties. The study highlights the augmentative effect of AP, a redox modulator, on hypoxic respiration, which may have a therapeutic potential.

Palmitato de ascorbil e acetato de tocoferol como antioxidantes metabólicos em larvas de dourado

“…Embora alguns autores citem que o palmitato de ascorbil é totalmente hidrolisado no intestino humano, formando o ácido ascórbico, May et al (1996) indicam que uma pequena fração é absorvida na sua forma íntegra e atua em meio lipídico no metabolismo. Pokorski et al (2003Pokorski et al ( , 2004 observaram, em gatos, a deposição do palmitato de ascorbil após o fornecimento na dieta, e demonstraram que parte do palmitato de ascorbil foi absorvido pelo trato gastrointestinal e depositado sem sofrer mudanças estruturais, similarmente ao ocorrido no presente trabalho. Entretanto, provavelmente a maior parte do palmitato de ascorbil absorvido, na forma de ácido ascórbico derivado da hidrolização do palmitato de ascorbil, resultou nas maiores concentrações de ácido ascórbico nas larvas de dourado, alimentadas com rações com a suplementação de 100 e 1.000 mg kg -1 de palmitato de ascorbil.…”

Biomedical Vignette

“…The idea that a redox pathway may be involved in chemoreceptor triggering comes from fi nding ascorbate in the carotid body and its depletion in hypoxia [8]. Pokorski et al [25] examined in an in vivo electrophysiological study the effect of ascorbyl palmitate on hypoxic respiration in anesthetized cats. They reported that treatment with ascorbyl palmitate augments hypoxic respiration.…”