Evaluation of immunotoxicity of sodium metavanadate following drinking water exposure in female B6C3F1/N mice in a 28-day study

Abstract

Sodium metavanadate (NaVO₃ ) is a pentavalent vanadium compound used in the metal industry and dietary supplements; human exposure occurs through inhalation of fumes and dust and ingestion of NaVO₃ -containing products. The objective of this study was to assess the potential immunotoxicity of NaVO₃ . Female B6C3F1/N mice were exposed to 0-500 ppm NaVO₃ in drinking water for 28 days and evaluated for effects on immune cell populations and innate, cellular-mediated, and humoral-mediated immunity. There was a decreasing trend in body weight (BW) and BW gain in NaVO₃ exposed mice, with a decrease (p ≤ 0.05) in BW gain at ≥250 ppm, relative to control. Conversely, increasing trends in spleen weights and an increase (p ≤ 0.05) in the spleen:BW ratio at ≥250 ppm NaVO₃ were observed. NaVO₃ exposure altered antibody production against sheep red blood cells (SRBC). Antibody forming cells (AFC)/10⁶ spleen cells exhibited a decreasing trend, with a decrease (p ≤ 0.05) at 500 ppm NaVO₃ , concurrent with an increase in percent B cells. NaVO₃ had no effect on the serum anti-SRBC IgM antibody titers or anti-keyhole limpet hemocyanin antibody production. Exposure to NaVO₃ decreased the percentage of natural killer cells at all dose levels (p ≤ 0.05), with no effect on the lytic activity. NaVO₃ altered T-cell populations at 500 ppm but had no effect on T-cell proliferative responses or the lytic activity of cytotoxic T cells. Collectively, these data indicate that NaVO₃ exposure can adversely affect the immune system by inducing alterations in humoral-mediated immunity, specifically the AFC response, with no effect on cell-mediated or innate immunity.

Keywords: humoral immunity; vanadate.

Figure 1. Humoral mediated immune response to Sheep Red Blood Cells (SRBC) in female B6C3F1/N mice exposed to Sodium Metavanadate (NaVO₃) for 28 days

(A) Antibody Forming Cell (AFC)/10⁶ Spleen Cells, (B) AFC/Spleen, (C) Serum Anti-SRBC IgM Antibody Titer, (D) Total Spleen Cells and % B-cells. Mice were exposed to NaVO₃ via drinking water for 28 days, immunized with SRBC on day 24, and evaluated for the antibody forming response to SRBC via the AFC Plaque forming assay and the serum IgM antibody titer to SRBC as described in Methods. Statistically significant trend values: AFC/10⁶ Spleen Cells, Total Spleen Cells, % B-cells p≤0.01. Values represent the mean (± SEM) from 7–8 animals per group. * Value significantly different from vehicle control *p≤0.05, **p≤0.01. CPS=cyclophosphamide (positive control)

Figure 2. Humoral mediated immune response to Sheep Red Blood Cells (SRBC) and to Keyhole Limpet Hemocyanin (KLH) in female B6C3F1/N mice exposed to Sodium Metavanadate (NaVO₃) for 28 days

(A) Anti-SRBC IgM producing B-cells/10⁶ Spleen Cells, (B) Anti-SRBC IgM producing B-cells/Spleen, (C) Serum Anti-KLH IgM Antibody Titer, (D) Serum Anti-KLH IgG Antibody Titer. Mice were exposed to NaVO₃ via drinking water for 28 days. The remaining spleen cell suspensions from the animals referenced in Figure 1 were added to an ELISPOT plate coated with SRBC membranes and evaluated for IgM producing B-cells as described in Methods. Mice in the groups C and D were immunized with KLH on day 14 and evaluated for the antibody forming response to KLH via the serum IgM antibody titer to KLH as described in Methods. Statistically significant trend values: Anti-SRBC IgM producing B-cells/10⁶ Spleen Cells p ≤0.05; Anti-SRBC IgM producing B-cells/Spleen p ≤0.01. Values represent the mean (± SEM) from 7–8 animals per group. * Value significantly different from vehicle control *p≤0.05, **p≤0.01. CPS=cyclophosphamide (positive control)