Exhaustive exercise results in inflammation and oxidative stress, which can damage tissue. Previous studies have shown that vitamin D has both anti-inflammatory and antiperoxidative activity. Therefore, we aimed to test if vitamin D could reduce the damage caused by exhaustive exercise. Rats were randomized to one of four groups: control, vitamin D, exercise, and vitamin D+exercise. Exercised rats received an intravenous injection of vitamin D (1 ng/mL) or normal saline after exhaustive exercise. Blood pressure, heart rate, and blood samples were collected for biochemical testing. Histological examination and immunohistochemical (IHC) analyses were performed on lungs and kidneys after the animals were sacrificed. In comparison to the exercise group, blood markers of skeletal muscle damage, creatine kinase and lactate dehydrogenase, were significantly (P < 0.05) lower in the vitamin D+exercise group. The exercise group also had more severe tissue injury scores in the lungs (average of 2.4 ± 0.71) and kidneys (average of 3.3 ± 0.6) than the vitamin D-treated exercise group did (1.08 ± 0.57 and 1.16 ± 0.55). IHC staining showed that vitamin D reduced the oxidative product 4-Hydroxynonenal in exercised animals from 20.6% to 13.8% in the lungs and from 29.4% to 16.7% in the kidneys. In summary, postexercise intravenous injection of vitamin D can reduce the peroxidation induced by exhaustive exercise and ameliorate tissue damage, particularly in the kidneys and lungs.
The cell membrane folate receptor is a potential molecular target for tumor-selective drug delivery. To probe structural requirements for folate receptor targeting with low molecular weight radiometal chelates, specifically the role of the amino acid fragment of folic acid (pteroylglutamic acid) in mediating targeting selectivity, the amide-linked conjugate pteroyl-NHCH(2)CH(2)OCH(2)CH(2)OCH(2)CH(2)NH-DTPA was prepared by a three-step procedure from pteroic acid, 2,2'-(ethylenedioxy)-bis(ethylamine), and t-Bu-protected DTPA. This conjugate, 1-{2-[2-[(2-(biscarboxymethyl-amino)ethyl)-carboxymethyl-amino]ethyl]-carboxymethyl-amino}-acetylamino-3,6-dioxa-8-pteroylamino-octane (1), was employed for synthesis of the corresponding (111)In(III) radiopharmaceutical. Following intravenous administration to athymic mice, the (111)In complex of 1 was found to selectively localize in folate receptor-positive human KB tumor xenografts and to afford prolonged tumor retention of the (111)In radiolabel (5.4 +/- 0.8, 5.6 +/- 1.1, and 3.6 +/- 0.6% of the injected dose per gram of tumor at 1, 4, and 24 h, respectively). The observed tumor localization was effectively blocked by co-administration of folic acid with the (111)In-1 complex, consistent with a folate receptor-mediated targeting process. In control studies, tumor targeting with this pteroic acid conjugate appears as effective as that seen using (111)In-DTPA-folate, a radiopharmaceutical that has progressed to clinical trials for detection of folate receptor-expressing gynecological tumors.
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