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. 2016:2016:7276463.
doi: 10.1155/2016/7276463. Epub 2016 Dec 25.

Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

Leticia Riverón-Negrete  1 , Gloria Sicilia-Argumedo  1 , Carolina Álvarez-Delgado  2 , Elvia Coballase-Urrutia  3 , Jonathan Alcántar-Fernández  1 , Cristina Fernandez-Mejia  1
Affiliations

Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

Leticia Riverón-Negrete et al. Biomed Res Int. 2016.

Abstract

Pharmacological concentrations of biotin have pleiotropic effects. Several reports have documented that biotin supplementation decreases hyperglycemia. We have shown that a biotin-supplemented diet increased insulin secretion and the mRNA abundance of proteins regulating insulin transcription and secretion. We also found enlarged pancreatic islets and modified islet morphology. Other studies have shown that pharmacological concentrations of biotin modify tissue structure. Although biotin administration is considered safe, little attention has been given to its effect on tissue structure. In this study, we investigated the effect of biotin supplementation on hepatic morphology and liver toxicity markers. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 8 weeks. Versus the control mice, biotin-supplemented mice had an altered portal triad with dilated sinusoids, increased vascularity, and bile conducts. Furthermore, we observed an increased proportion of nucleomegaly and binucleated hepatocytes. In spite of the liver morphological changes, no differences were observed in the serum liver damage indicators, oxidative stress markers, or antioxidant enzymes. Our data demonstrate for the first time that biotin supplementation affects liver morphology in normal mice, and that these modifications are not paralleled with damage markers.

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Conflict of interest statement

The authors declare that there are no competing interests regarding the publication of this paper.

Figures

Figure 1
Figure 1
Effect of biotin supplementation on liver malondialdehyde and reduced and oxidized glutathione in mice fed a biotin-supplemented diet for 8 weeks. (a) Malondialdehyde concentrations. Values represent the mean ± SEM of 5 mice from each group. (b) Reduced and oxidized glutathione. Black bars: control group; patterned bars: biotin-supplemented group. Values represent the mean ± SEM of 8 mice from each group. All measurements were performed in triplicate.   NS p > 0.050.
Figure 2
Figure 2
Effect of biotin supplementation on superoxide dismutase and catalase activity in mice fed a biotin-supplemented diet for 8 weeks. (a) Liver superoxide dismutase activity. Values represent the mean ± SEM of 5 mice from each group. (b) Liver catalase activity. Black bars: control group; patterned bars: biotin-supplemented group. Values represent the mean ± SEM of 9 mice from each group. All measurements were performed in triplicate.   NS p > 0.050.
Figure 3
Figure 3
Effect of biotin supplementation on liver morphology in mice fed a biotin-supplemented diet for 8 weeks. Paraffin sections stained by hematoxylin and eosin. (a) Control group's representative image showing a normal portal triad. (b) Supplemented group. Left panel: representative image, showing an altered triad with dilated sinusoids and increased number of bile ducts. Right panel: enlarged portal vein with adjacent portal vein branch. pv: portal vein; ha: hepatic artery; bd: bile duct; ds: dilated sinusoids; pvb: portal vein branch. Scale bar represents 100 μm.
Figure 4
Figure 4
Effect of biotin supplementation on binucleated hepatocytes and nucleomegaly in mice fed a biotin-supplemented diet for 8 weeks. (a) Hematoxylin and eosin representative image of hepatocytes from control and biotin-supplemented group (right) showing mono and binucleated hepatocytes. (b) Quantification of binucleated hepatocytes per field. (c) Hematoxylin and eosin images of hepatocytes from control and biotin-supplemented group (right) showing nuclei <12 and >12 μm. (d) Nuclei quantification >12 μm per field. Black bars: control group; patterned bars: biotin-supplemented group. Values represent the mean ± SEM of 9 mice per group. ∗ p < 0.050 compared to the control group.
Figure 5
Figure 5
Effect of biotin supplementation on nitric oxide concentrations in mice fed a biotin-supplemented diet for 8 weeks. Values represent the mean ± SEM of 9 mice from each group. Measurements were performed in triplicate. Black bars: control group; patterned bars: biotin-supplemented group.   NS p > 0.050.
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