Differential toxicity of Mn2+ and Mn3+ to rat liver tissues: oxidative damage, membrane fluidity and histopathological changes.
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 (Mn(2+)) and trivalent manganese (Mn(3+)). The present study was designed to evaluate and compare the effects of Mn(2+) and Mn(3+) on oxidative hepatic damage, membrane fluidity and histopathological changes in rats. Rats exposed to Mn(2+) or Mn(3+) (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, Mn(2+) and Mn(3+) 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 Mn(2+) and Mn(3+) inhibit the normal physiological functioning of the liver. Under the experimental conditions used, the adverse effects of Mn(2+) were more severe than those of Mn(3+).
Huang
Peili
P
Department of Toxicology and Sanitary Chemistry, School of Public Health and Family Medicine, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China.
Li
Guojun
G
Chen
Chunxia
C
Wang
Hui
H
Han
Ying
Y
Zhang
Shuhua
S
Xiao
Yang
Y
Zhang
Man
M
Liu
Na
N
Chu
Jinhua
J
Zhang
Long
L
Sun
Zhiwei
Z
D000818:Animals; D008099:Liver / Q000187:drug effects*; D008297:Male; D008345:Manganese / Q000633:toxicity*; D008560:Membrane Fluidity / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D008345:Manganese