Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration
Modulation of the AMP-activated protein kinase (AMPK) pathway activity is considered to be a promising option in the development of approaches to chronic alcoholic hepatitis treatment. Phenformin, which is a biguanide, has been reported to increase AMPK activity. The aim of this work was to estimat...
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2024-06-01
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| Series: | The Ukrainian Biochemical Journal |
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| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2024/06/Mykytenko_96_3.pdf |
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| author | A. Mykytenko O. Akimov G. Yeroshenko K. Neporada |
| author_facet | A. Mykytenko O. Akimov G. Yeroshenko K. Neporada |
| author_sort | A. Mykytenko |
| collection | DOAJ |
| description | Modulation of the AMP-activated protein kinase (AMPK) pathway activity is considered to be a promising option in the development of approaches to chronic alcoholic hepatitis treatment. Phenformin, which is a biguanide, has been reported to increase AMPK activity. The aim of this work was to estimate the effect of phenformin as AMPK activator on the development of oxidative-nitrosative stress in the liver of rats under conditions of long-term ethanol administration. The experiments were performed on 24 male Wistar rats, divided into 4 groups: control; animals, which received phenformin hydrochloride orally at a dose of 10 mg/kg daily for 63 days; animals with a forced intermittent alcoholization for 5 days by intraperitoneal administration of 16.5% ethanol solution in 5% glucose at the rate of 4 ml/kg b.w. and subsequent transfer to 10% ethanol as the only source of drinking; animals with chronic alcohol hepatitis simulation and phenformin administration. Superoxide dismutase, catalase, NO synthase isoforms activity, superoxide anion radical production, concentration of malonic dialdehyde, peroxynitrite, nitrites, nitrosothiols concentration and oxidative modification of proteins (OMP) were estimated in liver homogenates. The increased production of oxygen and nitrogen active forms and OMP intensification in the liver of rats under long-term administration of ethanol was detected. Phenformin introduction under long-term ethanol administration was shown to limit the excess peroxynitrite formation and to prevent oxidative damage to rat liver proteins. |
| format | Article |
| id | doaj-art-ffa5992f75024931a534f0601cc21b05 |
| institution | OA Journals |
| issn | 2409-4943 2413-5003 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj-art-ffa5992f75024931a534f0601cc21b052025-08-20T02:02:32ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032024-06-01963223010.15407/ubj96.03.022Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administrationA. Mykytenko0https://orcid.org/0000-0002-4205-2699O. Akimov1https://orcid.org/0000-0002-4958-3695G. Yeroshenko2K. Neporada3https://orcid.org/0000-0001-5430-346XDepartment of Bioorganic and Biological Chemistry, Poltava State Medical University, Poltava, UkraineDepartment of Pathophysiology, Poltava State Medical University, Poltava, UkraineDepartment of Medical Biology, Poltava State Medical University, Poltava, UkraineDepartment of Bioorganic and Biological Chemistry, Poltava State Medical University, Poltava, UkraineModulation of the AMP-activated protein kinase (AMPK) pathway activity is considered to be a promising option in the development of approaches to chronic alcoholic hepatitis treatment. Phenformin, which is a biguanide, has been reported to increase AMPK activity. The aim of this work was to estimate the effect of phenformin as AMPK activator on the development of oxidative-nitrosative stress in the liver of rats under conditions of long-term ethanol administration. The experiments were performed on 24 male Wistar rats, divided into 4 groups: control; animals, which received phenformin hydrochloride orally at a dose of 10 mg/kg daily for 63 days; animals with a forced intermittent alcoholization for 5 days by intraperitoneal administration of 16.5% ethanol solution in 5% glucose at the rate of 4 ml/kg b.w. and subsequent transfer to 10% ethanol as the only source of drinking; animals with chronic alcohol hepatitis simulation and phenformin administration. Superoxide dismutase, catalase, NO synthase isoforms activity, superoxide anion radical production, concentration of malonic dialdehyde, peroxynitrite, nitrites, nitrosothiols concentration and oxidative modification of proteins (OMP) were estimated in liver homogenates. The increased production of oxygen and nitrogen active forms and OMP intensification in the liver of rats under long-term administration of ethanol was detected. Phenformin introduction under long-term ethanol administration was shown to limit the excess peroxynitrite formation and to prevent oxidative damage to rat liver proteins.http://ukrbiochemjournal.org/wp-content/uploads/2024/06/Mykytenko_96_3.pdfamp-activated protein kinase.chronic alcoholic hepatitisliveroxidative and nitrosative stressphenformin |
| spellingShingle | A. Mykytenko O. Akimov G. Yeroshenko K. Neporada Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration The Ukrainian Biochemical Journal amp-activated protein kinase. chronic alcoholic hepatitis liver oxidative and nitrosative stress phenformin |
| title | Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration |
| title_full | Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration |
| title_fullStr | Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration |
| title_full_unstemmed | Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration |
| title_short | Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration |
| title_sort | phenformin attenuates the oxidative nitrosative stress in the liver of rats under long term ethanol administration |
| topic | amp-activated protein kinase. chronic alcoholic hepatitis liver oxidative and nitrosative stress phenformin |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2024/06/Mykytenko_96_3.pdf |
| work_keys_str_mv | AT amykytenko phenforminattenuatestheoxidativenitrosativestressintheliverofratsunderlongtermethanoladministration AT oakimov phenforminattenuatestheoxidativenitrosativestressintheliverofratsunderlongtermethanoladministration AT gyeroshenko phenforminattenuatestheoxidativenitrosativestressintheliverofratsunderlongtermethanoladministration AT kneporada phenforminattenuatestheoxidativenitrosativestressintheliverofratsunderlongtermethanoladministration |