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Effects of selenium supplementation on atopic dermatitis (AD) were investigated by administering seleno-L-methionine (SeMet) using a mouse model of AD caused by repeated application of 2,4,6-trinitrochlorobenzene (TNCB). BALB/c mice were sensitized with TNCB to the abdomen on day -7; then, TNCB was applied repeatedly to each ear three times a week from days 0 to 23. SeMet was orally administered to the mice from days 0 to 23. The efficacy of SeMet on AD was assessed by measuring ear thickness, histologic evaluation, serum total immunoglobulin (Ig) E levels, and expression of interleukin (IL)-4 in the ear and superficial parotid lymph node. Ear thickness was remarkably increased by repeated application of TNCB, and SeMet significantly suppressed ear thickness in BALB/c mice. SeMet inhibited epidermal hyperplasia and dense infiltration of inflammatory cells. The number of TNCB-induced mast cells was significantly decreased by SeMet. Serum total IgE levels that increased by the repeated application of TNCB were significantly suppressed by SeMet. Repeated application of TNCB induced expression of IL-4, a T-helper (Th) 2 cytokine, in the ear and superficial parotid lymph node of BALB/c mice and its expression was significantly inhibited by SeMet. These results demonstrated that SeMet supplementation suppresses AD-like skin lesions in BALB/c mice and inhibits the expression of total IgE and IL-4.

The protective effects of seleno-L-methionine (SeMet) on oxidative stress in pancreatic islets were investigated with a short-term nicotinamide (NA) and streptozotocin (STZ)-induced diabetic mouse model. ICR mice were intraperitoneally injected twice with 100 mg/kg STZ and 120 mg/kg NA at a 1-d interval and were then orally administered 158 µg Se/kg SeMet with free access to a selenium-deficient diet for 5 weeks. Administration of SeMet significantly improved the levels of glycated hemoglobin (HbA1c), non-fasting and oral glucose tolerance-tested (OGTT) blood glucose, plasma adiponectin and hepatic glycogen that deteriorated by NA/STZ treatment. However, supplementary SeMet did not restore non-fasting plasma insulin levels in NA/STZ treatment group and significantly suppressed OGTT plasma insulin levels in the control group. Although SeMet significantly suppressed 8-hydroxy-2'-deoxyguanosine density in pancreatic islets, SeMet did not restore insulin density. The hepatic and pancreatic mRNA levels of glutathione peroxidase 1 (GPX1) increased by NA/STZ treatment or SeMet administration. These results suggest that although a physiological level of SeMet improves glucose tolerance by exhibiting insulin-mimetic activity in a short-term induced diabetic mouse model under insufficient Se status, the suppression of pancreatic oxidative stress with the induction GPX1 by SeMet supplementation is unlikely to restore insulin storage and secretion.

The effects of administering the selenocompounds, sodium selenite, methylseleninic acid (MSA), and seleno-L-methionine (SeMet) on glucose tolerance were compared in the nicotinamide (NA) and streptozotocin (STZ)-induced diabetic mouse model. ICR mice were intraperitoneally treated twice with STZ (100 mg/kg) 15 min after an injection of NA (120 mg/kg) at a 1-d interval. Non-fasting blood glucose levels were then monitored weekly while orally administering the selenocompounds at 158 µg Se/kg body weight with free access to a selenium-deficient diet for 5 weeks. The mean body weights of NA/STZ-induced diabetic mice were partly restored by the administration of selenocompounds, while SeMet led to a higher selenium content and glutathione peroxidase 1 activity in the pancreas. Non-fasting and oral glucose tolerance-tested blood glucose levels, which were elevated by NA/STZ, were significantly suppressed by the administration of SeMet. These results suggest that SeMet may improve glucose tolerance in a NA/STZ-induced mild diabetic mouse model by increasing bioavailability in the pancreas.

To clarify the relationship between selenium supplementation and type I allergic reaction, we investigated the effect of seleno-L-methionine (SeMet) supplementation on the active cutaneous anaphylaxis (ACA) reaction and cytokine production in splenocytes. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), and SeMet was administered orally for 2 weeks followed by a challenge with OVA to induce an ACA reaction. SeMet supplementation suppressed the ACA reaction in a dose-dependent manner. Plasma OVA-specific immunoglobulin E (IgE) level was strongly inhibited in SeMet-supplemented mice compared with control mice. The mRNA expression levels of the T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 in the spleen of SeMet-supplemented mice were lower than those in control mice. The mRNA expression level of a Th1 cytokine, interferon (IFN)-γ, in the spleen of SeMet-supplemented mice was higher than that in control mice. Splenocytes restimulated with OVA in vitro from SeMet-supplemented mice produced lower amounts of IL-4 and IL-13 than those of control mice and higher amounts of IFN-γ than those from the control mice. These results suggest that oral SeMet supplementation suppresses OVA-induced ACA reaction by lowered Th2 cytokine production and augmenting Th1 cytokine production.