Ammonia-induced mitochondrial dysfunction and energy metabolism disturbances in isolated brain and liver mitochondria, and the effect of taurine administration: relevance to hepatic encephalopathy treatment

Abstract

IntroductionAmmonia-induced oxidative stress, mitochondrial dysfunction, and energy crisis are known as some the major mechanisms of brain injury in hepatic encephalopathy (HE). Hyperammonemia also affects the liver and hepatocytes. Therefore, targeting mitochondria seems to be a therapeutic point of intervention in the treatment of HE. Taurine is an abundant amino acid in the human body. Several biological functions including the mitochondrial protective properties are attributed to this amino acid. The aim of this study is to evaluate the effect of taurine administration on ammonia-induced mitochondrial dysfunction.Material and methodsIsolated mice liver and brain mitochondria were exposed to different concentrations of ammonia (1, 5, 10, and 20 mM) and taurine (1, 5, and 10 mM), and several mitochondrial indices were assessed.ResultsIt was found that ammonia inhibited mitochondrial dehydrogenases activity caused collapse of mitochondrial membrane potential (MMP), induced mitochondrial swelling (MPP), and increased reactive oxygen species (ROS) in isolated liver and brain mitochondria. Furthermore, a significant amount of lipid peroxidation (LPO), along with glutathione (GSH) and ATP depletion, was detected in ammonia exposed mitochondria. Taurine administration (5 and 10 mM) mitigated ammonia-induced mitochondrial dysfunction.ConclusionsThe current investigation demonstrates that taurine is instrumental in preserving brain and liver mitochondrial function in a hyperammonemic environment. The data suggest taurine as a potential protective agent with a therapeutic capability against hepatic encephalopathy and hyperammonemia.

Taurine supplementation abates cirrhosis-associated locomotor dysfunction

“…It has been established that hyperammonemia leads to a brain energy crisis [ 77 , 78 ]. Previously we found that TAU could preserve brain mitochondrial function in hyperammonemic conditions [ 79 , 80 ]. Hence, another dominant mechanism for the neuroprotective effects of TAU in cirrhosis could be mediated through its impact on cellular mitochondria.…”

Taurine mitigates cirrhosis-associated heart injury through mitochondrial-dependent and antioxidative mechanisms

“…Although the mechanisms underlying the antioxidative effects of Tau need more investigations to be precisely clarified, some investigations mentioned the regulatory effects of this amino acid on mitochondrial function as a pivotal mechanism for its antioxidative properties [ 43 , 114 - 116 ]. Interestingly, it has been shown that Tau effectively mitigated mitochondria-facilitated ROS formation and enhanced mitochondrial ATP content [ 12 , 36 , 37 , 117 - 119 ]. The protective properties of this amino acid might be mediated through its effect on mitochondria protein synthesis (e.g., mitochondria respiratory chain components) [ 120 , 121 ].…”

“…It has been found that Tau protects heart tissue against toxic insults by alleviation of oxidative stress and its associated events [ 10 , 26 - 31 ]. Interestingly, recent studies mentioned that the antioxidant effect of Tau is indirectly mediated by the effects of this amino acid on cellular mitochondria [ 16 , 32 - 37 ].…”

Neuroprotective Effect of Nortriptyline in Overt Hepatic Encephalopathy Through Attenuation of Mitochondrial Dysfunction

“…Furthermore, apart from the role in CytC translocation, the mPTP opening can disrupt the proton gradient, which in turn mediates the concurrent dissipation of mitochondrial membrane potential (△Ψ m ; Precht et al., 2005 ). The mitochondrial events described earlier are believed to mediate the mitochondrial dysfunction and eventual demise of the host neuron in various CNS pathologies associated with OHE ( Lax et al., 2017 ; Niknahad et al., 2017 ). In this regard, the pharmacological means to interfere one or more steps in these cascades can offer the opportunity to retard or even stop the progression of OHE; however, the therapeutic potential of the pharmacological inhibition of the opening of mPTP on HE must be further investigated.…”