Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury

Reza Heidari; Akram Jamshidzadeh; Mohammad Mehdi Ommati; Elaheh Rashidi; Forouzan Khodaei; Ala Sadeghi; Arghavan Hosseini; Hossein Niknahad

doi:10.5114/ceh.2019.85071

Abstract

2/2019 vol. 5

Original paper

Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury

Reza Heidari ¹

,

Akram Jamshidzadeh ²

,

Mohammad Mehdi Ommati ¹

,

Elaheh Rashidi ²

,

Forouzan Khodaei ²

,

Ala Sadeghi ²

,

Arghavan Hosseini ²

,

Hossein Niknahad ^{1, 2}

Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Clin Exp HEPATOL 2019; 5, 2: 109–117

DOI: https://doi.org/10.5114/ceh.2019.85071

Online publish date: 2019/05/23

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AMA

Heidari R, Jamshidzadeh A, Ommati M, et al. Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury. Clinical and Experimental Hepatology. 2019;5(2):109-117. doi:10.5114/ceh.2019.85071.

APA

Heidari, R., Jamshidzadeh, A., Ommati, M., Rashidi, E., Khodaei, F., & Sadeghi, A. et al. (2019). Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury. Clinical and Experimental Hepatology, 5(2), 109-117. https://doi.org/10.5114/ceh.2019.85071

Chicago

Heidari, Reza, Akram Jamshidzadeh, Mohammad Mehdi Ommati, Elaheh Rashidi, Forouzan Khodaei, Ala Sadeghi, and Arghavan Hosseini et al. 2019. "Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury". Clinical and Experimental Hepatology 5 (2): 109-117. doi:10.5114/ceh.2019.85071.

Harvard

Heidari, R., Jamshidzadeh, A., Ommati, M., Rashidi, E., Khodaei, F., Sadeghi, A., Hosseini, A., and Niknahad, H. (2019). Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury. Clinical and Experimental Hepatology, 5(2), pp.109-117. https://doi.org/10.5114/ceh.2019.85071

MLA

Heidari, Reza et al. "Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury." Clinical and Experimental Hepatology, vol. 5, no. 2, 2019, pp. 109-117. doi:10.5114/ceh.2019.85071.

Vancouver

Heidari R, Jamshidzadeh A, Ommati M, Rashidi E, Khodaei F, Sadeghi A et al. Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury. Clinical and Experimental Hepatology. 2019;5(2):109-117. doi:10.5114/ceh.2019.85071.

Aim of the study

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome ensuing from liver failure. The liver is the major site of ammonia detoxification in the human body. Hence, acute and chronic liver dysfunction can lead to hyperammonemia. Manganese (Mn) is a trace element incorporated in several physiological processes in the human body. Mn is excreted through bile. It has been found that cirrhosis is associated with hyperammonemia as well as body Mn accumulation. The brain is the primary target organ for both ammonia and Mn toxicity. On the other hand, brain mitochondria impairment is involved in the mechanism of Mn and ammonia neurotoxicity.

Material and methods

The current study was designed to evaluate the effect of Mn and ammonia and their combination on mitochondrial indices of functionality in isolated brain mitochondria. Isolated brain mitochondria were exposed to increasing concentrations of ammonia and Mn alone and/or in combination and several mitochondrial indices were assessed.

Results

The collapse of mitochondrial membrane potential, increased mitochondrial permeabilization, reactive oxygen species formation, and a significant decrease in mitochondrial dehydrogenase activity and ATP content were evident in Mn-exposed (0.005-1 mM) brain mitochondria. On the other hand, ammonia (0.005-0.5 mM) caused no significant changes in brain mitochondrial function. It was found that co-exposure of the brain mitochondria to Mn and ammonia causes more evident mitochondrial impairment in comparison with Mn and/or ammonia alone.

Conclusions

These data indicate additive toxicity of ammonia and Mn in isolated brain mitochondria exposed to these neurotoxins.

Keywords

brain injury, cirrhosis, energy crisis, hepatic encephalopathy, locomotor dysfunction

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