Tissue-Specific Effects of Vitamin E Supplementation

Abstract

A multivitamin and mineral supplementation study of 6 weeks was conducted with male and female mice. The control group received a standard dose of vitamins and minerals of 1× the Recommended Daily Intake (RDI), whereas a second group received 3× RDI. A third group received a high dose of vitamin E (25× RDI), close to the upper limit of toxicity (UL), but still recommended and considered to be harmless and beneficial. The high dose of vitamin E caused a number of beneficial, but also adverse effects. Different biomarkers of tissue toxicity, oxidative stress related processes and inflammation were determined. These biomarkers did not change in plasma and erythrocytes to a large extent. In the liver of male mice, some beneficial effects were observed by a lower concentration of several biomarkers of inflammation. However, in the kidney of male mice, a number of biomarkers increased substantially with the higher dose of vitamin E, indicating tissue toxicity and an increased level of inflammation. Since this dose of vitamin E, which is lower than the UL, cause some adverse effects, even after a short exposure period, further studies are required to reconsider the UL for vitamin E.

Keywords: Il-6; MCP-1; PAI-1; TNF-α; oxidative stress; resistin; vitamin E; α-tocopherol.

Figure 1

(A) Plasma activities in male; and (B) female mice of alkaline phosphatase (ALP), alanine aminotransferase (ALT) and plasma concentrations of reactive oxygen metabolites (ROM), biological antioxidant potential (BAP) and total thiol levels in proteins (TTP) after exposure to the three different diets. The levels of ALP, ALT and BAP were multiplied by a factor of 3, 10 and 0.1, respectively to fit in the figure. The levels of feed B were tested statistically relative to those of feed A, and the levels of feed C relative to those of feed B. No statistical differences were found.

Figure 2

(A) Activities of catalase (CAT), glutathion peroxidase (GPX), gluthation reductase (GR), superoxide dismutase (SOD) and concentration of total glutathione (totGSH) in erythrocytes from male (Figure A); and (B) female mice. The levels of CAT, GPX, GR and SOD were multiplied by a factor of 10, 5, 0.3 and 2, respectively to fit in the figure. The levels of feed B were tested statistically relative to those of feed A, and the levels of feed C relative to those of feed B. * p < 0.05, ** p < 0.01.

Figure 3

(A) Activities of ALT, AST and LDH, and concentrations of BAP and TTP in the post-mitochondrial supernatant of liver tissue of male mice. The levels of LDH, BAP and TTL were multiplied by a factor of 0.2, 10 and 20, respectively to fit in the figure; (B) Concentrations of MCP-1, IL-6, TNF-α, PAI-1 and resistin in the post-mitochondrial supernatant of liver tissue of male mice. The levels of IL-6, TNFα and resistin were multiplied by a factor of 4 to fit in the figure. The levels of feed B were tested statistically relative to those of feed A, and the levels of feed C relative to those of feed B. * p < 0.05, ** p < 0.01.

Figure 4

(A) Activities of ALT, AST and LDH, and concentrations of BAP and TTP in the post-mitochondrial supernatant of liver tissue of female mice. The levels of AST, LDH, BAP and TTL were multiplied by a factor of 0.5, 0.2, 10 and 10, respectively to fit in the figure; (B). Concentrations of MCP-1, IL-6, TNF-α, PAI-1 and resistin in the post-mitochondrial supernatant of liver tissue of female mice. The levels of IL-6, TNF-α and resistin were multiplied by a factor of 4, 3 and 4, respectively to fit in the figure. The levels of feed B were tested statistically relative to those of feed A, and the levels of feed C relative to those of feed B. * p < 0.05.

Figure 5

(A) Activities of ALT, AST and LDH, and concentrations of BAP and TTP in the post-mitochondrial supernatant of kidney tissue of male mice. The levels of ALT, LDH, BAP and TTL were multiplied by a factor of 10, 0.1, 5 and 20, respectively, to fit in the figure; (B) Concentrations of MCP-1, IL-6, TNF-α, PAI-1 and resistin in the post-mitochondrial supernatant of kidney tissue of male mice. The levels of MCP-1, IL-6, TNF-α and resistin were multiplied by a factor of 5, 10, 20 and 0.25, respectively, to fit in the figure. The levels of feed B were tested statistically relative to those of feed A, and the levels of feed C relative to those of feed B. * p < 0.05, ** p < 0.01.

Figure 6

(A) Activities of ALT, AST and, LDH, and concentrations of BAP and TTP in the post-mitochondrial supernatant of kidney tissue of female mice. The levels of ALT, LDH, BAP and TTL were multiplied by a factor of 10, 0.1, 5 and 20, respectively, to fit in the figure; (B) Concentrations of MCP-1, IL-6, TNF-α, PAI-1 and resistin in the post-mitochondrial supernatant of kidney tissue of female mice. The levels of MCP-1, IL-6, TNF-α and resistin were multiplied by a factor of 5, 10, 20 and 5, respectively, to fit in the figure. The levels of feed B were tested statistically relative to those of feed A, and the levels of feed C relative to those of feed B. * p < 0.05; ** p < 0.01.