Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity

Hossein Niknahad; Ali Mobasheri; Abdollah Arjmand; Elahe Rafiei; Sepideh Alidaee; Hadi Razavi; Sara Bagheri; Heresh Rezaei; Samira Sabouri; Asma Najibi; Forouzan Khodaei; Seyyed Mohammad Amin Kashani; Mohammad Mehdi Ommati; Reza Heidari

doi:10.1016/j.heliyon.2023.e20557

Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity

Hossein Niknahad, Ali Mobasheri^*, Abdollah Arjmand, Elahe Rafiei, Sepideh Alidaee, Hadi Razavi, Sara Bagheri, Heresh Rezaei, Samira Sabouri, Asma Najibi, Forouzan Khodaei, Seyyed Mohammad Amin Kashani, Mohammad Mehdi Ommati^*, Reza Heidari^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: of the study: Hepatic encephalopathy (HE) is a complication in which brain ammonia (NH₄ ⁺) levels reach critically high concentrations because of liver failure. HE could lead to a range of neurological complications from locomotor and behavioral disturbances to coma. Several tactics have been established for subsiding blood and brain NH₄ ⁺. However, there is no precise intervention to mitigate the direct neurological complications of NH₄ ⁺. Purpose: It has been found that oxidative stress, mitochondrial damage, and neuro-inflammation play a fundamental role in NH₄ ⁺ neurotoxicity. Piracetam is a drug used clinically in neurological complications such as stroke and head trauma. Piracetam could significantly diminish oxidative stress and improve brain mitochondrial function. Research methods: In the current study, piracetam (100 and 500 mg/kg, oral) was used in a mice model of HE induced by thioacetamide (TA, 800 mg/kg, single dose, i.p). Results: Significant disturbances in animals’ locomotor activity, along with increased oxidative stress biomarkers, including reactive oxygen species formation, protein carbonylation, lipid peroxidation, depleted tissue glutathione, and decreased antioxidant capacity, were evident in the brain of TA-treated mice. Meanwhile, mitochondrial permeabilization, mitochondrial depolarization, suppression of dehydrogenases activity, and decreased ATP levels were found in the brain of the TA group. The level of pro-inflammatory cytokines was also significantly high in the brain of HE animals. Conclusion: It was found that piracetam significantly enhanced mice's locomotor activity, blunted oxidative stress biomarkers, decreased inflammatory cytokines, and improved mitochondrial indices in hyperammonemic mice. These data suggest piracetam as a neuroprotective agent which could be repurposed for the management of HE.

Original language	English
Article number	e20557
Journal	Heliyon
Volume	9
Issue number	10
DOIs	https://doi.org/10.1016/j.heliyon.2023.e20557
Publication status	Published - Oct 2023

Keywords

Brain injury
Hepatic encephalopathy
Liver failure
Locomotor disturbances
Pharmacotherapy

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Niknahad, H., Mobasheri, A., Arjmand, A., Rafiei, E., Alidaee, S., Razavi, H., Bagheri, S., Rezaei, H., Sabouri, S., Najibi, A., Khodaei, F., Kashani, S. M. A., Ommati, M. M., & Heidari, R. (2023). Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity. Heliyon, 9(10), Article e20557. https://doi.org/10.1016/j.heliyon.2023.e20557

@article{3f7ab708a9924ca08657cf763ef25f3b,

title = "Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity",

abstract = "Background: of the study: Hepatic encephalopathy (HE) is a complication in which brain ammonia (NH4 +) levels reach critically high concentrations because of liver failure. HE could lead to a range of neurological complications from locomotor and behavioral disturbances to coma. Several tactics have been established for subsiding blood and brain NH4 +. However, there is no precise intervention to mitigate the direct neurological complications of NH4 +. Purpose: It has been found that oxidative stress, mitochondrial damage, and neuro-inflammation play a fundamental role in NH4 + neurotoxicity. Piracetam is a drug used clinically in neurological complications such as stroke and head trauma. Piracetam could significantly diminish oxidative stress and improve brain mitochondrial function. Research methods: In the current study, piracetam (100 and 500 mg/kg, oral) was used in a mice model of HE induced by thioacetamide (TA, 800 mg/kg, single dose, i.p). Results: Significant disturbances in animals{\textquoteright} locomotor activity, along with increased oxidative stress biomarkers, including reactive oxygen species formation, protein carbonylation, lipid peroxidation, depleted tissue glutathione, and decreased antioxidant capacity, were evident in the brain of TA-treated mice. Meanwhile, mitochondrial permeabilization, mitochondrial depolarization, suppression of dehydrogenases activity, and decreased ATP levels were found in the brain of the TA group. The level of pro-inflammatory cytokines was also significantly high in the brain of HE animals. Conclusion: It was found that piracetam significantly enhanced mice's locomotor activity, blunted oxidative stress biomarkers, decreased inflammatory cytokines, and improved mitochondrial indices in hyperammonemic mice. These data suggest piracetam as a neuroprotective agent which could be repurposed for the management of HE.",

keywords = "Brain injury, Hepatic encephalopathy, Liver failure, Locomotor disturbances, Pharmacotherapy",

author = "Hossein Niknahad and Ali Mobasheri and Abdollah Arjmand and Elahe Rafiei and Sepideh Alidaee and Hadi Razavi and Sara Bagheri and Heresh Rezaei and Samira Sabouri and Asma Najibi and Forouzan Khodaei and Kashani, {Seyyed Mohammad Amin} and Ommati, {Mohammad Mehdi} and Reza Heidari",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = oct,

doi = "10.1016/j.heliyon.2023.e20557",

language = "English",

volume = "9",

number = "10",

}

Niknahad, H, Mobasheri, A, Arjmand, A, Rafiei, E, Alidaee, S, Razavi, H, Bagheri, S, Rezaei, H, Sabouri, S, Najibi, A, Khodaei, F, Kashani, SMA, Ommati, MM & Heidari, R 2023, 'Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity', Heliyon, vol. 9, no. 10, e20557. https://doi.org/10.1016/j.heliyon.2023.e20557

Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity. / Niknahad, Hossein; Mobasheri, Ali; Arjmand, Abdollah et al.
In: Heliyon, Vol. 9, No. 10, e20557, 10.2023.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity

AU - Niknahad, Hossein

AU - Mobasheri, Ali

AU - Arjmand, Abdollah

AU - Rafiei, Elahe

AU - Alidaee, Sepideh

AU - Razavi, Hadi

AU - Bagheri, Sara

AU - Rezaei, Heresh

AU - Sabouri, Samira

AU - Najibi, Asma

AU - Khodaei, Forouzan

AU - Kashani, Seyyed Mohammad Amin

AU - Ommati, Mohammad Mehdi

AU - Heidari, Reza

PY - 2023/10

Y1 - 2023/10

N2 - Background: of the study: Hepatic encephalopathy (HE) is a complication in which brain ammonia (NH4 +) levels reach critically high concentrations because of liver failure. HE could lead to a range of neurological complications from locomotor and behavioral disturbances to coma. Several tactics have been established for subsiding blood and brain NH4 +. However, there is no precise intervention to mitigate the direct neurological complications of NH4 +. Purpose: It has been found that oxidative stress, mitochondrial damage, and neuro-inflammation play a fundamental role in NH4 + neurotoxicity. Piracetam is a drug used clinically in neurological complications such as stroke and head trauma. Piracetam could significantly diminish oxidative stress and improve brain mitochondrial function. Research methods: In the current study, piracetam (100 and 500 mg/kg, oral) was used in a mice model of HE induced by thioacetamide (TA, 800 mg/kg, single dose, i.p). Results: Significant disturbances in animals’ locomotor activity, along with increased oxidative stress biomarkers, including reactive oxygen species formation, protein carbonylation, lipid peroxidation, depleted tissue glutathione, and decreased antioxidant capacity, were evident in the brain of TA-treated mice. Meanwhile, mitochondrial permeabilization, mitochondrial depolarization, suppression of dehydrogenases activity, and decreased ATP levels were found in the brain of the TA group. The level of pro-inflammatory cytokines was also significantly high in the brain of HE animals. Conclusion: It was found that piracetam significantly enhanced mice's locomotor activity, blunted oxidative stress biomarkers, decreased inflammatory cytokines, and improved mitochondrial indices in hyperammonemic mice. These data suggest piracetam as a neuroprotective agent which could be repurposed for the management of HE.

AB - Background: of the study: Hepatic encephalopathy (HE) is a complication in which brain ammonia (NH4 +) levels reach critically high concentrations because of liver failure. HE could lead to a range of neurological complications from locomotor and behavioral disturbances to coma. Several tactics have been established for subsiding blood and brain NH4 +. However, there is no precise intervention to mitigate the direct neurological complications of NH4 +. Purpose: It has been found that oxidative stress, mitochondrial damage, and neuro-inflammation play a fundamental role in NH4 + neurotoxicity. Piracetam is a drug used clinically in neurological complications such as stroke and head trauma. Piracetam could significantly diminish oxidative stress and improve brain mitochondrial function. Research methods: In the current study, piracetam (100 and 500 mg/kg, oral) was used in a mice model of HE induced by thioacetamide (TA, 800 mg/kg, single dose, i.p). Results: Significant disturbances in animals’ locomotor activity, along with increased oxidative stress biomarkers, including reactive oxygen species formation, protein carbonylation, lipid peroxidation, depleted tissue glutathione, and decreased antioxidant capacity, were evident in the brain of TA-treated mice. Meanwhile, mitochondrial permeabilization, mitochondrial depolarization, suppression of dehydrogenases activity, and decreased ATP levels were found in the brain of the TA group. The level of pro-inflammatory cytokines was also significantly high in the brain of HE animals. Conclusion: It was found that piracetam significantly enhanced mice's locomotor activity, blunted oxidative stress biomarkers, decreased inflammatory cytokines, and improved mitochondrial indices in hyperammonemic mice. These data suggest piracetam as a neuroprotective agent which could be repurposed for the management of HE.

KW - Brain injury

KW - Hepatic encephalopathy

KW - Liver failure

KW - Locomotor disturbances

KW - Pharmacotherapy

UR - http://www.scopus.com/inward/record.url?scp=85173149692&partnerID=8YFLogxK

U2 - 10.1016/j.heliyon.2023.e20557

DO - 10.1016/j.heliyon.2023.e20557

M3 - Article

AN - SCOPUS:85173149692

SN - 2405-8440

VL - 9

JO - Heliyon

JF - Heliyon

IS - 10

M1 - e20557

ER -

Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity

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