Aims: The free radical scavenger and nitric oxide synthase cofactor, 5,6,7,, plays a well-documented role in many disorders associated with oxidative stress, including normal tissue radiation responses. Radiation exposure is associated with decreased BH4 levels, while BH4 supplementation attenuates aspects of radiation toxicity. The endogenous synthesis of BH4 is catalyzed by the enzyme guanosine triphosphate cyclohydrolase I (GTPCH1), which is regulated by the inhibitory GTP cyclohydrolase I feedback regulatory protein (GFRP). We here report and characterize a novel, Cre-Lox-driven, transgenic mouse model that overexpresses Gfrp. Results: Compared to control littermates, transgenic mice exhibited high transgene copy numbers, increased Gfrp mRNA and GFRP expression, enhanced GFRP-GTPCH1 interaction, reduced BH4 levels, and low glutathione (GSH) levels and differential mitochondrial bioenergetic profiles. After exposure to total body irradiation, transgenic mice showed decreased BH4/7,8-dihydrobiopterin ratios, increased vascular oxidative stress, and reduced white blood cell counts compared with controls. Innovation and Conclusion: This novel Gfrp knock-in transgenic mouse model allows elucidation of the role of GFRP in the regulation of BH4 biosynthesis. This model is a valuable tool to study the involvement of BH4 in whole body and tissue-specific radiation responses and other conditions associated with oxidative stress.

The purpose of the study was to investigate the role of flavonoids from Emilia sonchifolia (ES) on the progression of selenite-induced cataract. The antioxidant property of the flavonoids isolated from ES was assessed by measuring its capacity to inhibit superoxide production and serum oxidation in vitro in comparison with quercetin. Based on these experiments, an in vivo study was conducted to evaluate the modulatory effects of the flavonoids against selenite cataract. Cataract was induced by a single subcutaneous injection of sodium selenite (4 mg/kg body weight). The treatment group received flavonoids from ES (1 mg/kg) and this was compared with the quercetin treated group. Lens opacification was monitored by a slit lamp microscope and classified into six stages. Activity of the antioxidant enzymes - superoxide dismutase and catalase - and the level of lipid peroxidation products thiobarbituric acid reacting substances and reduced glutathione were studied. Slit lamp examination showed that the flavonoid fraction from ES could modulate the progression of cataract. Activities of superoxide dismutase, catalase and reduced glutathione were found to be increased in the ES treated groups, while thiobarbituric acid reacting substances were decreased compared with the selenite-induced group. The results suggest that flavonoids from ES can modulate lens opacification and oxidative stress in selenite-induced cataract.

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Countermeasures against radiation are critically needed. Ideally, these measures would be easy to store, easy to administer and have minimal toxicity. We used oral delivery of interleukin 11 (IL11) in mice exposed to lethal doses of total-body irradiation (TBI). Animals were given IL11 by gavage at various daily doses beginning 24 h after TBI, which continued for 5 days. At a TBI of 9.0 Gy, mice treated with IL11 had a 70% survival at 30 days compared with control group survival of 25% (P = 0.035). At 10.0 Gy, treated animals had 50% survival at 30 days compared with no survivors in the control group. Treated animals had significant improvement in intestinal mucosal surface area and crypt survival. In addition bacterial translocation of coliform bacteria was significantly less in the treated animals. Systemic absorption of IL11 was low in treated animals and effects on the hematopoietic cells were not seen. Serum citrulline levels rebounded significantly faster after irradiation in the IL11 treated animals, indicating quicker recovery of small intestine health. These data suggest that IL11 given orally protects the intestinal mucosa from radiation damage and that this compound is beneficial as a mitigating agent even when started 24 h after radiation exposure.

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