Alogliptin abates memory injuries of hepatic encephalopathy induced by acute paracetamol intoxication via switching-off autophagy-related apoptosis

Saad, Marina; Rastanawi, Alyasaa A.; El-Yamany, Muhammed F.

doi:10.1016/j.lfs.2018.10.069

Cited by 17 publications

(10 citation statements)

References 68 publications

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“…APAP‐induced ALF in mice leads to brain oedema and coma together with increased blood ammonia levels 19 . Additionally, activation of intracellular signalling mechanisms, including elevated levels of cytokines, activation of brain transcription factors (increased levels of NF‐kB, NRf2 etc), induction of oxidative stress, glial fibrillary acidic protein expression, as well as autophagy‐related events have been observed in the brains of these animals 19‐27 …”

Section: Current Animal Models Of Hementioning

confidence: 99%

2021 ISHEN guidelines on animal models of hepatic encephalopathy

DeMorrow

Cudalbu

Davies

et al. 2021

Liver International

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This working group of the International Society of Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) was commissioned to summarize and update current efforts in the development and characterization of animal models of hepatic encephalopathy (HE). As defined in humans, HE in animal models is based on the underlying degree and severity of liver pathology. Although hyperammonemia remains the key focus in the pathogenesis of HE, other factors associated with HE have been identified, together with recommended animal models, to help explore the pathogenesis and pathophysiological mechanisms of HE. While numerous methods to induce liver failure and disease exist, less have been characterized with neurological and neurobehavioural impairments. Moreover, there still remains a paucity of adequate animal models of Type C HE induced by alcohol, viruses and non‐alcoholic fatty liver disease; the most common etiologies of chronic liver disease.

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Section: Current Animal Models Of Hementioning

confidence: 99%

2021 ISHEN guidelines on animal models of hepatic encephalopathy

DeMorrow

Cudalbu

Davies

et al. 2021

Liver International

View full text Add to dashboard Cite

show abstract

“…79 Acute APAP intoxication disturbs neurotransmitters including γ-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine, and acetylcholine, increases oxidative stress and reactive astrogliosis in the brain, and consequently induces HE. 80,81 Moreover, similar to the case in antibiotics, maternal use of APAP also induces neurofunctional impairments in the progeny. 82 In addition to the fact that APAP also is distributed in the brain, which directly affects brain function, the gut-brain axis may play a part therein.…”

Section: Chemotherapeutics-induced Gastrointestinal Toxicity (Cigt) and Gut Dysbiosismentioning

confidence: 86%

“…Although alterations in the brain caused by APAP have long been considered secondary effects of acute liver injury, recently APAP is found to be a cannabinoid system modulator and cause “in situ” toxicity in the brain, especially at high doses 79 . Acute APAP intoxication disturbs neurotransmitters including γ‐aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine, and acetylcholine, increases oxidative stress and reactive astrogliosis in the brain, and consequently induces HE 80,81 . Moreover, similar to the case in antibiotics, maternal use of APAP also induces neurofunctional impairments in the progeny 82 .…”

Section: Drugs Modify the Microbiome To Elicit Toxicitymentioning

confidence: 99%

Connecting the dots: Targeting the microbiome in drug toxicity

Luo

Zhou

2021

Medicinal Research Reviews

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The gut microbiota has a vast influence on human health and its role in initiating, aggravating, or ameliorating diseases is beginning to emerge. Recently, its contribution to heterogeneous toxicological responses is also gaining attention, especially in drug-induced toxicity. Whether they are orally administered or not, drugs may interact with the gut microbiota directly or indirectly, which leads to altered toxicity. Present studies focus more on the unidirectional influence of how xenobiotics disturb intestinal microbial composition and functions, and thus induce altered homeostasis. However, interactions between the gut microbiota and xenobiotics are bidirectional and the impact of the gut microbiota on xenobiotics, especially on drugs, should not be neglected. Thus, in this review, we focus on how the gut microbiota modulates drug toxicity by highlighting the microbiome, microbial enzyme, and microbial metabolites. We connect the dots between drugs, the microbiome, microbial enzymes or metabolites, drug metabolites, and host

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“…The cage was thoroughly cleaned with 75% alcohol before the next rat test. The Y-maze test was performed to evaluate the spatial orientation learning ability of rats [19]. The Ymaze test apparatus included three closed plastic arms with an angle of 120 °between them.…”

Section: Behavioral Testingmentioning

confidence: 99%

Role of SIRT1 in Hepatic Encephalopathy: In Vivo and In Vitro Studies Focusing on the NLRP3 Inflammasome

Jiao

Wang

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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Hepatic encephalopathy (HE) is a neuropsychiatric disorder resulting from acute or chronic liver failure. This study is aimed at investigating the therapeutic effects and mechanisms of SIRT1 in thioacetamide- (TAA-) induced rat HE models. A selective activator (CAY10602) and inhibitor (EX527) of SIRT1 were used in this study. All male rats were separated into control, TAA, CAY10602+TAA, and EX527+TAA groups. Histological damage, liver function, serum ammonia, behavioral changes, and brain oxidative stress were measured in each group. Western blotting was used to measure SIRT1, NLRP3, ASC, and IL-1β protein expression. The results showed that CAY10602 alleviated liver injury, improved neurological decline, reduced microglial activation and brain oxidative stress, and improved the survival rates of HE rats. Moreover, CAY10602 inhibited activation of the NLRP3 inflammasome in microglia of the brain cortex in HE rats. Next, cell experiments confirmed that CAY10602 inhibited activation of the NLRP3 inflammasome in BV2 microglial cells. However, inhibition of SIRT1 by EX527 or lentivirus could enhance activation of the NLRP3 inflammasome in this process. Finally, CAY10602 reduced the neurotoxicity induced by high levels of ammonia in HT22 cells. Taken together, CAY10602 alleviates TAA-induced HE by suppressing microglial activation and the NLRP3 inflammasome and reducing the neurotoxicity of NH4Cl in HT22 cells. A pharmacologic activator of SIRT1 may be a promising approach for the treatment of HE.

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Alogliptin abates memory injuries of hepatic encephalopathy induced by acute paracetamol intoxication via switching-off autophagy-related apoptosis

Cited by 17 publications

References 68 publications

2021 ISHEN guidelines on animal models of hepatic encephalopathy

2021 ISHEN guidelines on animal models of hepatic encephalopathy

Connecting the dots: Targeting the microbiome in drug toxicity

Role of SIRT1 in Hepatic Encephalopathy: In Vivo and In Vitro Studies Focusing on the NLRP3 Inflammasome

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