Manganese and Ammonia Interactions in the Brain of Cirrhotic Rats: Effects on Brain Ammonia Metabolism
Hepatic encephalopathy is a major complication of cirrhosis. Ammonia and manganese have been associated with hepatic encephalopathy underlying mechanisms. Motor impairment and brain edema are common signs of hepatic encephalopathy. In the present study a model of liver damage in rats was combined with ammonia and manganese exposure to evaluate the role of these substances separately and their interactions on brain glutamine, water content and motor coordination. Additionally, we explored brain levels of each substance -Mn and ammonia- in the presence or absence of the other. Liver damage was induced by bile duct ligation. Rats were exposed to MnCl2 in drinking water (1 mg Mn/ml) and to ammonia in chow pellets containing 20% ammonium acetate (w/w). As expected, manganese and ammonia levels increased in the brain of cirrhotic rats exposed to these substances; in these animals, glutamine brain levels also increased and positively correlated with tissue water content in cortex. A three way-ANOVA showed that manganese favored ammonia and glutamine accumulation in brain, and possibly their subsequent deleterious effects, as evidenced by the fact that manganese and ammonia accumulation in the brain of cirrhotic rats severely affected motor function. These results suggest that even when controlling ammonia levels in cirrhotic patients, reduction of manganese intake is also a potential strategy to be considered in clinical practice.
KeywordsHepatic encephalopathy Manganese Ammonia Cirrhosis Brain edema Glutamine
This work was financially supported by Consejo Nacional de Ciencia y Tecnología (CONACYT) grant No. 51541. S. Rivera-Mancía wants to thank the Biomedical Research Graduate Program, the Biomedical Research Institute and the National Autonomous University of Mexico for their support to carry out this work. Authors wish to thank Marisela Méndez-Armenta for liver histological preparations, Yessica Heras ans Rodolfo Pérez-Madrigal for their assistance in animal care and Elena Rivera-Mancía for reviewing this manuscript. S Rivera-Mancía receives a fellowship from CONACYT (203330). Instruments acquired with CONACYT grant 61327 were used to carry out this study.
Conflict of interest
The authors declare that they have no conflict of interest.
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