دورية أكاديمية
The short-term effects of berberine in the liver: Narrow margins between benefits and toxicity.
| العنوان: | The short-term effects of berberine in the liver: Narrow margins between benefits and toxicity. |
|---|---|
| المؤلفون: | Moreira ES; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., Ames-Sibin AP; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., Bonetti CI; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., Leal LE; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., Peralta RM; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., de Sá-Nakanishi AB; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., Comar JF; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., Bracht A; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil., Bracht L; Department of Biochemistry, State University of Maringá, Maringá, PR, Brazil. Electronic address: lbracht@uem.br. |
| المصدر: | Toxicology letters [Toxicol Lett] 2022 Sep 01; Vol. 368, pp. 56-65. Date of Electronic Publication: 2022 Aug 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Amsterdam, Elsevier/North Holland. |
| مواضيع طبية MeSH: | Berberine*/toxicity, Ammonia/metabolism ; Animals ; Gluconeogenesis ; Hypoglycemic Agents/pharmacology ; Liver ; Mitochondria, Liver ; NAD/metabolism ; Perfusion ; Pyruvic Acid/metabolism ; Rats |
| مستخلص: | Berberine is a plant alkaloid to which antihyperglycemic properties have been attributed. It is also known as an inhibitor of mitochondrial functions. In this work short-term translation of the latter effects on hepatic metabolism were investigated using the isolated perfused rat liver. Once-through perfusion with a buffered saline solution was done. At low portal concentrations berberine modified several metabolic pathways. It inhibited hepatic gluconeogenesis, increased glycolysis, inhibited ammonia detoxification, increased the cytosolic NADH/NAD + ratio and diminished the ATP levels. Respiration of intact mitochondria was impaired as well as the mitochondrial pyruvate carboxylation activity. These results can be regarded as evidence that the direct inhibitory effects of berberine on gluconeogenesis, mediated by both energy metabolism and pyruvate carboxylation inhibition, represent most likely a significant contribution to its clinical efficacy as an antihyperglycemic agent. However, safety concerns also arise because all effects occur at similar concentrations and there is a narrow margin between the expected benefits and toxicity. Even mild inhibition of gluconeogenesis is accompanied by diminutions in oxygen uptake and ammonia detoxification and increases in the NADH/NAD + ratio. All combined, desired and undesired effects could well in the end represent a deleterious combination of events leading to disruption of cellular homeostasis. (Copyright © 2022 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Alkaloid; Ammonia detoxification; Energy metabolism; Gluconeogenesis; Glycolysis |
| المشرفين على المادة: | 0 (Hypoglycemic Agents) 0I8Y3P32UF (Berberine) 0U46U6E8UK (NAD) 7664-41-7 (Ammonia) 8558G7RUTR (Pyruvic Acid) |
| تواريخ الأحداث: | Date Created: 20220813 Date Completed: 20220831 Latest Revision: 20220831 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.toxlet.2022.08.005 |
| PMID: | 35963428 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-3169 |
|---|---|
| DOI: | 10.1016/j.toxlet.2022.08.005 |