Excessive manganese alters serum biochemical indices, induces histopathological alterations, and activates apoptosis in liver and cerebrum of Jianzhou Da'er goat (Capra hircus)

The present study aimed to explore the toxic effects of excessive dietary Mn in livers and cerebrums of Jianzhou Da'er goat (Capra hircus). Three-month old goats were assigned into three groups: control group, fed on basal diet; Mn I group, fed on the basal diet mixed with MnCl2 (2.5 g/kg); Mn II group, fed on the basal diet mixed with MnCl2 (5 g/kg). Compared with the control group, the activities of serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the concentrations of interferon-gamma (IFN-gamma) in Mn I and Mn II groups were significantly increased, but the concentrations of IgG in Mn I and Mn II groups were significantly decreased (p < 0.05). The activities of superoxide dismutase (T-SOD), glutathione peroxidase (GSHPx), and the concentrations of glutathione (GSH) in Mn I and Mn II groups were significantly decreased, whereas the concentrations of malondialdehyde (MDA) in Mn I and Mn II groups were significantly increased in livers and cerebrums (p < 0.05). Moreover, the hepatocytes necrosed, inflammatory cells infiltrated, chromatin concentrated, mitochondrial cristae reduced in Mn I and Mn II groups. The nerve cells necrosed, blood vessels congested, inflammatory cells infiltrated, mitochondrial electron density and mitochondrial cristae decreased, and vacuolization increased in Mn I and Mn II groups. Furthermore, the mRNA expressions of tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor receptor type 1 (TNFR1), fas-associated protein via a death domain (FADD), Bcl2-associated X (Bax), cysteinyl aspartate specific proteinase 3, 8, 9 (Caspase-3, 8, 9) in Mn I and Mn II groups were significantly increased (p < 0.05), but the mRNA expressions of B-cell lymphoma-2 (Bcl-2) in Mn I and Mn II groups were significantly decreased (p < 0.05) in livers. The mRNA expressions of Bcl-2, Bax, Caspase-3, 9, 7, 12 in Mn I and Mn II groups were significantly increased (p < 0.05), however, the ratio of Bcl-2/Bax in Mn I and Mn II groups was significantly decreased (p < 0.05) in cerebrums. In summary, our results provided new insights for better understanding the mechanisms of Mn toxicity in Capra hircus.