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Differential toxicity of Mn2+ and Mn3+ to rat liver tissues: oxidative damage, membrane fluidity and
Peili Huang1, Guojun Li, Chunxia Chen
1Department of Toxicology and Sanitary Chemistry, School of Public Health and Family Medicine, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China.
Abstract:
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+).
Insights
Manganese (Mn) overexposure harms the liver. Both divalent (Mn(2+)) and trivalent (Mn(3+)) forms cause oxidative damage, alter membrane fluidity, and lead to histopathological changes in rat livers, with Mn(2+) showing more severe effects.
Area of Science:
- Toxicology
- Hepatology
- Environmental Health
Background:
- Manganese (Mn) toxicity is a growing concern, particularly neurotoxicity.
- Limited data exists on Mn's adverse effects on liver function.
- Mn exists physiologically as divalent (Mn(2+)) and trivalent (Mn(3+)) ions.
Purpose of the Study:
- To evaluate and compare the effects of Mn(2+) and Mn(3+) on oxidative hepatic damage.
- To assess impacts on liver membrane fluidity and histopathological alterations in rats.
Main Methods:
- Rats were exposed to Mn(2+) or Mn(3+) at 2.0mg Mn/kg body weight.
- Assessed enzymatic activity (SOD, GPx), oxidative stress markers (GSH, MDA), and membrane properties (Na(+),K(+)-ATPase, fluorescence anisotropy).
- Utilized light and electron microscopy for histopathological evaluation.
Main Results:
- Both Mn(2+) and Mn(3+) significantly inhibited SOD and GPx activity, decreased GSH, and increased MDA in liver tissues and hepatocyte nuclei.
- Reduced Na(+),K(+)-ATPase activity, decreased plasma membrane fluidity, and increased fluorescence anisotropy were observed.
- Histopathological changes included mononuclear cell infiltration, congestion, hepatocellular damage, necrosis, and mitochondrial alterations.
- Adverse effects of Mn(2+) were more pronounced than Mn(3+).
Conclusions:
- Both Mn(2+) and Mn(3+) impair normal liver physiological functions.
- Mn exposure induces significant oxidative stress and membrane damage in hepatic tissues.
- Mn(2+) exhibits a more severe hepatotoxic profile compared to Mn(3+) under the tested conditions.
