Iron deficiency is a common health problem. The most severe consequence of this disorder is iron deficiency anemia (IDA), which is considered the most common nutritional deficiency worldwide. Newborn piglets are an ideal model to explore the multifaceted etiology of IDA in mammals, as IDA is the most prevalent deficiency disorder throughout the early postnatal period in this species and frequently develops into a critical illness. Here, we report the very low expression of duodenal iron transporters in pigs during the first days of life. We postulate that this low expression level is why the iron demands of the piglet body are not met by iron absorption during this period. Interestingly, we found that a low level of duodenal divalent metal transporter 1 and ferroportin, two iron transporters located on the apical and basolateral membrane of duodenal absorptive enterocytes, respectively, correlates with abnormally high expression of hepcidin, despite the poor hepatic and overall iron status of these animals. Parenteral iron supplementation by a unique intramuscular administration of large amounts of iron dextran is current practice for the treatment of IDA in piglets. However, the potential toxicity of such supplemental iron implies the necessity for caution when applying this treatment. Here we demonstrate that a modified strategy for iron supplementation of newborn piglets with iron dextran improves the piglets' hematological status, attenuates the induction of hepcidin expression, and minimizes the toxicity of the administered iron. (Am J Pathol

Oxidative stress is involved in the pathogenesis of colon cancer. We wanted to elucidate at which stage of the disease this phenomenon occurs. In the examined groups of patients with colorectal cancer (CRC, n = 89), benign adenoma (AD, n = 77) and healthy volunteers (controls, n = 99), we measured: vitamins A, C and E in blood plasma, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in leukocytes and urine, leukocyte 8-oxoGua excision activity, mRNA levels of APE1, OGG1, 8-oxo-7,8-dihydrodeoxyguanosine 5'-triphosphate pyrophosphohydrolase (MTH1) and OGG1 polymorphism. The vitamin levels decreased gradually in AD and CRC patients. 8-OxodG increased in leukocytes and urine of CRC and AD patients. 8-OxoGua was higher only in the urine of CRC patients. 8-OxoGua excision was higher in CRC patients than in controls, in spite of higher frequency of the OGG1 Cys326Cys genotype, encoding a glycosylase with decreased activity. mRNA levels of OGG1 and APE1 increased in CRC and AD patients, which could explain increased 8-oxoGua excision rate in CRC patients. MTH1 mRNA was also higher in CRC patients. The results suggest that oxidative stress occurs in CRC and AD individuals. This is accompanied by increased transcription of DNA repair genes, and increased 8-oxoGua excision rate in CRC patients, which is, however, insufficient to counteract the increased DNA damage.

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Is oxidative damage of DNA responsible for physiological changes associated with aging? The authors note a positive correlation between the age of human subjects with the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in leukocyte DNA. The levels of urinary 8-oxo-7,8-dihydroguanine and 8-oxodG followed the same pattern of correlation. Age-dependent decline in the concentration of plasma vitamin C was also evident. These interesting observations in humans point towards the need to scrutinize in detail the role of oxidative DNA damage and compromised antioxidant defense systems in age-related physiological disorders.