l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures
Background and aims: Excessive amounts of bile acids (ΒΑ) exert hepatotoxic effects. We investigated the effects of glycochenodeoxycholic acid (GCDC) on mitochondrial function and insulin-like growth factor-1 (IGF-1) activity in hepatocytes and also examined if l-carnitine (CRNT) has any protective...
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Elsevier
2025-06-01
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| Series: | Endocrine and Metabolic Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666396125000354 |
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| author | Wafa'a Alqabandi Maira Alsaeid Gursev Dhaunsi |
| author_facet | Wafa'a Alqabandi Maira Alsaeid Gursev Dhaunsi |
| author_sort | Wafa'a Alqabandi |
| collection | DOAJ |
| description | Background and aims: Excessive amounts of bile acids (ΒΑ) exert hepatotoxic effects. We investigated the effects of glycochenodeoxycholic acid (GCDC) on mitochondrial function and insulin-like growth factor-1 (IGF-1) activity in hepatocytes and also examined if l-carnitine (CRNT) has any protective role. Methods: Primary hepatocyte cultures were treated with 0–100 μM GCDC with or without 5 mM l-carnitine (CRNT). DNA synthesis was measured by bromodeoxyuridine incorporation assay. Enzymic activities of carnitine palmitoyltransferase-1 (CPT-1), cytochrome c oxidase (CcO) and medium chain-acylCoA dehydrogenase (MCAD), were measured in hepatocyte homogenates. Expression of peroxisome proliferator activated receptor gamma coactivator 1-α (PGC-1α) and IGF-1 receptor (IGF-1R) was detected by RT- PCR and Western blot analysis, respectively. Results: Treatment with GCDC significantly decreased the enzymatic activity of MCAD, CPT-1 and CcO (P < 0.01), and mitochondrial ATP content. Additionally, GCDC significantly increased malondialdehyde (MDA) levels in mitochondria and downregulated PGC-1α (p < 0.01). Furthermore, the IGF-1-induced DNA synthesis and IGF-1R gene expression were also notably reduced in GCDC-treated hepatocytes. However, co-treatment with 5 mM CRNT markedly abrogated the GCDC-induced impairment of CcO activity and PGC-1α downregulation, while it had no effect on MCAD activity. In addition, CRNT treatment also restored the enzymatic activity of CPT-1 and the gene expression levels of IGF-1 in GCDC-treated hepatocytes (p < 0.05). Conclusions: GCDC-induced hepatotoxic effects could be triggered by mitochondrial dysfunction and impairment of IGF-1 activity. CRNT has potential beneficial effects against ΒΑ-induced cytotoxicity via enhancing the CPT-1 and CcO enzyme activities, and ATP production in addition to upregulation of PGC-1α and IGF-1R. |
| format | Article |
| id | doaj-art-ba3aafbc0465423abcff88fcc8a8f0f6 |
| institution | OA Journals |
| issn | 2666-3961 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Endocrine and Metabolic Science |
| spelling | doaj-art-ba3aafbc0465423abcff88fcc8a8f0f62025-08-20T01:52:25ZengElsevierEndocrine and Metabolic Science2666-39612025-06-011810024910.1016/j.endmts.2025.100249l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte culturesWafa'a Alqabandi0Maira Alsaeid1Gursev Dhaunsi2Corresponding author at: Department of Pediatrics, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait.; Department of Pediatrics, College of Medicine, Kuwait University, KuwaitDepartment of Pediatrics, College of Medicine, Kuwait University, KuwaitDepartment of Pediatrics, College of Medicine, Kuwait University, KuwaitBackground and aims: Excessive amounts of bile acids (ΒΑ) exert hepatotoxic effects. We investigated the effects of glycochenodeoxycholic acid (GCDC) on mitochondrial function and insulin-like growth factor-1 (IGF-1) activity in hepatocytes and also examined if l-carnitine (CRNT) has any protective role. Methods: Primary hepatocyte cultures were treated with 0–100 μM GCDC with or without 5 mM l-carnitine (CRNT). DNA synthesis was measured by bromodeoxyuridine incorporation assay. Enzymic activities of carnitine palmitoyltransferase-1 (CPT-1), cytochrome c oxidase (CcO) and medium chain-acylCoA dehydrogenase (MCAD), were measured in hepatocyte homogenates. Expression of peroxisome proliferator activated receptor gamma coactivator 1-α (PGC-1α) and IGF-1 receptor (IGF-1R) was detected by RT- PCR and Western blot analysis, respectively. Results: Treatment with GCDC significantly decreased the enzymatic activity of MCAD, CPT-1 and CcO (P < 0.01), and mitochondrial ATP content. Additionally, GCDC significantly increased malondialdehyde (MDA) levels in mitochondria and downregulated PGC-1α (p < 0.01). Furthermore, the IGF-1-induced DNA synthesis and IGF-1R gene expression were also notably reduced in GCDC-treated hepatocytes. However, co-treatment with 5 mM CRNT markedly abrogated the GCDC-induced impairment of CcO activity and PGC-1α downregulation, while it had no effect on MCAD activity. In addition, CRNT treatment also restored the enzymatic activity of CPT-1 and the gene expression levels of IGF-1 in GCDC-treated hepatocytes (p < 0.05). Conclusions: GCDC-induced hepatotoxic effects could be triggered by mitochondrial dysfunction and impairment of IGF-1 activity. CRNT has potential beneficial effects against ΒΑ-induced cytotoxicity via enhancing the CPT-1 and CcO enzyme activities, and ATP production in addition to upregulation of PGC-1α and IGF-1R.http://www.sciencedirect.com/science/article/pii/S2666396125000354Mitochondria IGF-1CarnitineBile acidsHepatocytes |
| spellingShingle | Wafa'a Alqabandi Maira Alsaeid Gursev Dhaunsi l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures Endocrine and Metabolic Science Mitochondria IGF-1 Carnitine Bile acids Hepatocytes |
| title | l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures |
| title_full | l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures |
| title_fullStr | l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures |
| title_full_unstemmed | l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures |
| title_short | l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures |
| title_sort | l carnitine protects against bile acid induced mitochondrial dysfunction and igf 1 impairment in hepatocyte cultures |
| topic | Mitochondria IGF-1 Carnitine Bile acids Hepatocytes |
| url | http://www.sciencedirect.com/science/article/pii/S2666396125000354 |
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