Differential toxicity of Mn²⁺ and Mn³⁺ to rat liver tissues: Oxidative damage, membrane fluidity and histopathological changes
2012
Huang, Peili | Li, Guojun | Chen, Chunxia | Wang, Hui | Han, Ying | Zhang, Shuhua | Xiao, Yang | Zhang, Man | Liu, Na | Chu, Jinhua | Zhang, Long | Sun, Zhiwei
Toxicity due to overexposure to manganese (Mn) is becoming increasingly prevalent. Mn-induced neurodegenerative toxicity has been demonstrated, but little is known concerning the adverse effects of the element on the liver. Under physiological conditions, manganese primarily exists as divalent manganese (Mn²⁺) and trivalent manganese (Mn³⁺). The present study was designed to evaluate and compare the effects of Mn²⁺ and Mn³⁺ on oxidative hepatic damage, membrane fluidity and histopathological changes in rats. Rats exposed to Mn²⁺ or Mn³⁺ (2.0mg Mn/kg body weight) showed significant inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as well as decreased levels of glutathione (GSH) and increased levels of malondialdehyde (MDA) in liver tissues. We also showed a significant inhibition of SOD activity and increased MDA levels in hepatocyte nuclei. We also observed reduced Na⁺,K⁺-ATPase activity, increased MDA levels and decreased plasma membrane fluidity, which was accompanied by an increase of fluorescence anisotropy (r) values, in hepatic plasma membranes. In addition, Mn²⁺ and Mn³⁺ both caused histopathological changes, such as mononuclear cell infiltration, congestion, enlargement of the veins and sinusoids, hepatocellular damage, necrotic changes, mitochondrial hyperplasia, swelling and vacuolization, as determined by light and electron microscopy. Taken together, these data suggest that both Mn²⁺ and Mn³⁺ inhibit the normal physiological functioning of the liver. Under the experimental conditions used, the adverse effects of Mn²⁺ were more severe than those of Mn³⁺.
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