Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism.

During therapeutic hyperbaric oxygenation lymphocytes are exposed to high partial pressures of oxygen. This study aimed to analyze the mechanism of apoptosis induction by hyperbaric oxygen. For intervals of 0.5-4 h Jurkat-T-cells were exposed to ambient air or oxygen atmospheres at 1-3 absolute atmospheres. Apoptosis was analyzed by phosphatidylserine externalization, caspase-3 activation and DNA-fragmentation using flow cytometry. Apoptosis was already induced after 30 min of hyperbaric oxygenation (HBO, P < 0.05). The death receptor Fas was downregulated. Inhibition of caspase-9 but not caspase-8 blocked apoptosis induction by HBO. Hyperbaric oxygen caused a loss of mitochondrial membrane potential and caspase-9 induction. The mitochondrial pro-survival protein Bcl-2 was upregulated, and antagonizing Bcl-2 function potentiated apoptosis induction by HBO. In conclusion, a single exposure to hyperbaric oxygenation induces lymphocyte apoptosis by a mitochondrial and not a Fas-related mechanism. Regulation of Fas and Bcl-2 may be regarded as protective measures of the cell in response to hyperbaric oxygen.

Low serum alpha-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis.

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.

Topical alpha-tocotrienol supplementation inhibits lipid peroxidation but fails to mitigate increased transepidermal water loss after benzoyl peroxide treatment of human skin.

Benzoyl peroxide (BPO) is a commonly used drug in the treatment of acne vulgaris, but it induces unwanted side effects related to stratum corneum (SC) function. Since it has been recently shown to oxidize SC antioxidants, it was hypothesized that antioxidant supplementation may mitigate the BPO-induced SC changes. To test this, 11 subjects were selected to be topically supplemented with alpha-tocotrienol (5% w/vol) for 7 d on defined regions of the upper back, while the contralateral region was used for vehicle-only controls. Starting on day 8, all test sites were also treated with BPO (10%) for 7 d; the alpha-tocotrienol supplementation was continued throughout the study. A single dose of BPO depleted 93.2% of the total vitamin E. While continuing the BPO exposure for 7 d further depleted vitamin E in both vehicle-only and alpha-tocotrienol-treated sites, significantly more vitamin E remained in the alpha-tocotrienol-treated areas. Seven BPO applications increased lipid peroxidation. Alpha-tocotrienol supplementation significantly mitigated the BPO-induced lipid peroxidation. The transepidermal water loss was increased 1.9-fold by seven BPO applications, while there was no difference between alpha-tocotrienol treatment and controls. The data suggest that alpha-tocotrienol supplementation counteracts the lipid peroxidation but not the barrier perturbation in the SC induced by 10% BPO.