Effects of antioxidant MnTBAP on angiogenesis in newborn mice with hyperoxic lung injury.

BACKGROUND: Oxygen toxicity mediated by reactive oxygen species (ROS) plays an essential role in the development of bronchopulmonary dysplasia in premature infants. By reducing oxidative stress, antioxidants protect the immature lung. We studied the effects of MnTBAP, a catalytic antioxidant on angiogenesis and alveolar growth following neonatal hyperoxia. METHODS: Newborn mouse litters randomized to room air (RA) or >95% O2 for 72 hours from day 4 (D4) to D7 to receive either MnTBAP (10 mg/kg/d) or saline intraperitoneally (every 24 h for three doses). Lungs harvested for angiogenic gene expression, protein expression, and histopathology post-hyperoxia exposure. Radial alveolar count (RAC), mean linear intercept (MLI) and vessel density assessed by histopathology. RESULTS: Angiogenic gene expression was significantly lower in the hyperoxia group compared to the RA group. The protein expression for VEGF and its receptor, VEGFR1, was significantly lower following treatment with MnTBAP compared to hyperoxia alone. Expression of VEGFR2, Angiopoietin-1 and TIE2, were substantially higher in the RA groups compared to hyperoxia groups with or without MnTBAP. Hyperoxia groups demonstrated alveolar simplification. MnTBAP reduced vessel density and failed to improve alveolar growth following hyperoxia. CONCLUSIONS: MnTBAP, a catalytic antioxidant, does not offer protection from hyperoxia-induced alveolar impairment. The lack of angiogenic upregulation by MnTBAP may contribute to alveolar simplification in newborn mice.

Preparation of pH-sensitive liposomes retaining SOD mimic and their anticancer effect.

We prepared an anticancer drug based on a pH-sensitive liposome retaining Fe-porphyrin as an SOD mimic. The liposomes contained cationic/anionic lipid combinations and were composed of Fe-porphyrin, 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine, dimethylditetradecylammonium bromide, sodium oleate, and Tween-80. The Fe-porphyrin was released from the liposome at low pH, and the cytotoxicity for cancer cells by the liposome depended on the acidic environments of the endosomes in the cells. Furthermore, although the liposome exhibited an excellent anticancer effect on a gastric cancer cell line, the SOD activity of Fe-porphyrin was shown to have a significant influence on the cytotoxicity toward cancer cells. These findings suggest that the pH-sensitive liposome retaining the Fe-porphyrin as an SOD mimic promises to be a novel anticancer drug for endosomal escape.