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; Rafiei, Elahe; Alidaee, Sepideh; Razavi, Hadi; Bagheri, Sara; Rezaei, Heresh; Sabouri, Samira; Najibi, Asma; Khodaei, Forouzan; Kashani, Seyyed Mohammad Amin; Ommati, Mohammad Mehdi; Heidari, Reza (2023-09-29)
Elsevier
29.09.2023
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), e20557. https://doi.org/10.1016/j.heliyon.2023.e20557
https://creativecommons.org/licenses/by-nc-nd/4.0/
© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://creativecommons.org/licenses/by-nc-nd/4.0/
© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://creativecommons.org/licenses/by-nc-nd/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202312053501
https://urn.fi/URN:NBN:fi:oulu-202312053501
Tiivistelmä
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.
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.
Kokoelmat
- Avoin saatavuus [38319]
Ellei muuten mainita, aineiston lisenssi on https://creativecommons.org/licenses/by-nc-nd/4.0/