We have investigated the hypothesis that a lipid-soluble derivative of ascorbic acid, ascorbyl-6-palmitate (AP), could serve as a carrier of ascorbate into neural tissues. Ascorbate could then exert its physiological effects in the biomembranes that are the target sites of the cellular signaling pathways which are normally hardly accessible to this water-soluble compound. The potential role of AP would require that it penetrates into tissues. The major objective of the study was to determine whether ascorbate could be recovered from cerebral cortex and carotid body tissues, both sensitive to the hypoxic stimulus, after AP given by gavage. Biological samples were analyzed by HPLC for the determination of ascorbate. We found that ascorbate was recovered from the tissues studied. Its content was higher in both tissues, by nearly an order of magnitude, after ingestion of AP than after ingestion of ascorbic acid, and the ascorbate level was higher in the carotid body than in the cortex. Hypoxia decreased the ascorbate content which implies physiological activity of ascorbate carried alongside the AP molecule. The lipophilic AP was able to cross biological barriers and satisfied the tissue demand for ascorbate better than the hydrophilic form. AP should be considered as the preferred form of transport of ascorbate into neural tissues. The results of this study suggest wider pharmacological applications of ascorbyl palmitate.

We have investigated the hypothesis that a lipid-soluble derivative of ascorbic acid, ascorbyl-6-palmitate (AP), could serve as a carrier of ascorbate into neural tissues. Ascorbate could then exert its physiological effects in the biomembranes that are the target sites of the cellular signaling pathways which are normally hardly accessible to this water-soluble compound. The potential role of AP would require that it penetrates into tissues. The major objective of the study was to determine whether ascorbate could be recovered from cerebral cortex and carotid body tissues, both sensitive to the hypoxic stimulus, after AP given by gavage. Biological samples were analyzed by HPLC for the determination of ascorbate. We found that ascorbate was recovered from the tissues studied. Its content was higher in both tissues, by nearly an order of magnitude, after ingestion of AP than after ingestion of ascorbic acid, and the ascorbate level was higher in the carotid body than in the cortex. Hypoxia decreased the ascorbate content which implies physiological activity of ascorbate carried alongside the AP molecule. The lipophilic AP was able to cross biological barriers and satisfied the tissue demand for ascorbate better than the hydrophilic form. AP should be considered as the preferred form of transport of ascorbate into neural tissues. The results of this study suggest wider pharmacological applications of ascorbyl palmitate.

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Diabetes, apart from generalized neuropathy and microangiopathy, involves tissue hypoxia, which may drive chronic proinflammatory state. However, studies on the ventilatory control in diabetes are sparse and conflicting. In this study we examined the function and morphology of diabetic carotid bodies (CBs). Diabetes was evoked in Wistar rats with streptozotocin (70 mg/kg, i.p.). The acute hypoxic ventilatory responses (HVR) to 12 and 8 % O(2) were investigated in conscious untreated rats after 2 and 4 weeks in a plethysmographic chamber. CBs were dissected and subjected to morphologic investigations: (1) electron transmission microscopy for ultrastructure and (2) laser scanning confocal microscopy to visualize the microvascular bed in sections labeled with the lectin Griffonia simplicifolia-I (GSI), an endothelial cell marker, and fluorescein isothiocyanate (FITC). All findings were referenced to the normal healthy rats. We found that diabetes distinctly dampened the HVR. At the ultrastructural level, the diabetic CB displayed proliferation of connective tissue and neovascularization deranging the interglomal structure, and lengthening the O(2) diffusion path from capillaries to chemoreceptor cells. The chemoreceptor cells remained largely unchanged. The endothelial cell labeling confirmed the intensive angiopathy and the induction of microvessel growth. We conclude that diabetes hampers the chemical regulation of ventilation due to remodeling of CB parenchyma, which may facilitate chronic hypoxia and inflammation in the organ.

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