β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats
Abstract Background Non-alcoholic steatohepatitis (NASH) is a chronic disease characterized by inflammation, steatosis, and liver fibrosis. The liver is particularly affected by alterations in lipid metabolism. Our aim was to evaluate the effect of β-hydroxyphosphocarnitine (β-HPC) on NASH induced i...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | BMC Pharmacology and Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40360-022-00613-2 |
| _version_ | 1797998409452355584 |
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| author | Janet Sánchez-Quevedo Emmanuel Ocampo-Rodríguez Elizabeth Alvarez-Ayala Anahí Rodríguez-López Miguel Angel Duarte-Vázquez Jorge Luis Rosado Lourdes Rodríguez-Fragoso |
| author_facet | Janet Sánchez-Quevedo Emmanuel Ocampo-Rodríguez Elizabeth Alvarez-Ayala Anahí Rodríguez-López Miguel Angel Duarte-Vázquez Jorge Luis Rosado Lourdes Rodríguez-Fragoso |
| author_sort | Janet Sánchez-Quevedo |
| collection | DOAJ |
| description | Abstract Background Non-alcoholic steatohepatitis (NASH) is a chronic disease characterized by inflammation, steatosis, and liver fibrosis. The liver is particularly affected by alterations in lipid metabolism. Our aim was to evaluate the effect of β-hydroxyphosphocarnitine (β-HPC) on NASH induced in rats. Methods NASH was produced via the ad libitum daily chronic administration of a fructose solution (400 kcal) for 9 weeks, an oral dose of fat solution (16 kcal) for 7 weeks and a subcutaneous injection of CCl4 (30%) two times a week for 2 weeks to Wistar rats. To evaluate the effect of β-HPC, a dose of 100 mg/kg was administered perorally for 4 weeks and its biochemical and hepatic effects on rats with NASH were analyzed. Serum levels of glucose, triglycerides, cholesterol, and liver enzymes were quantified. Histological changes were evaluated on slices stained with H&E, trichromic and PAS. Glycogen content was measured in liver samples. α-SMA and SREBP-1 immunopositive cells were identified in liver tissue. Results NASH was characterized by elevated triglycerides, elevated liver damage enzymes, and the presence of necrosis, inflammation, steatosis, and fibrosis. Significant amounts of glycogen were found, along with α-SMA positive cells in fibrosis areas. The over-expression of SREBP-1 in cytoplasm and nuclei was evident. Animals with NASH treated with β-HPC showed a significant reduction in inflammation, necrosis, and glycogen content in the liver. A reduction in α-SMA and SREBP-1 immunopositive cells correlated with a significant reduction in the degree of fibrosis and steatosis found in liver tissue. β-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with β-HPC did not show any alterations in liver enzyme function. Conclusions Our research shows that β-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting β-HPC could be potentially used in the treatment of NASH. |
| first_indexed | 2024-04-11T10:48:20Z |
| format | Article |
| id | doaj.art-f66d83181c884916b00c621d17a3709b |
| institution | Directory Open Access Journal |
| issn | 2050-6511 |
| language | English |
| last_indexed | 2024-04-11T10:48:20Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj.art-f66d83181c884916b00c621d17a3709b2022-12-22T04:29:00ZengBMCBMC Pharmacology and Toxicology2050-65112022-09-0123111210.1186/s40360-022-00613-2β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in ratsJanet Sánchez-Quevedo0Emmanuel Ocampo-Rodríguez1Elizabeth Alvarez-Ayala2Anahí Rodríguez-López3Miguel Angel Duarte-Vázquez4Jorge Luis Rosado5Lourdes Rodríguez-Fragoso6Facultad de Farmacia, Universidad Autónoma del Estado de MorelosFacultad de Farmacia, Universidad Autónoma del Estado de MorelosFacultad de Farmacia, Universidad Autónoma del Estado de MorelosFacultad de Farmacia, Universidad Autónoma del Estado de MorelosNucitec S.A. de C.V.Nucitec S.A. de C.V.Facultad de Farmacia, Universidad Autónoma del Estado de MorelosAbstract Background Non-alcoholic steatohepatitis (NASH) is a chronic disease characterized by inflammation, steatosis, and liver fibrosis. The liver is particularly affected by alterations in lipid metabolism. Our aim was to evaluate the effect of β-hydroxyphosphocarnitine (β-HPC) on NASH induced in rats. Methods NASH was produced via the ad libitum daily chronic administration of a fructose solution (400 kcal) for 9 weeks, an oral dose of fat solution (16 kcal) for 7 weeks and a subcutaneous injection of CCl4 (30%) two times a week for 2 weeks to Wistar rats. To evaluate the effect of β-HPC, a dose of 100 mg/kg was administered perorally for 4 weeks and its biochemical and hepatic effects on rats with NASH were analyzed. Serum levels of glucose, triglycerides, cholesterol, and liver enzymes were quantified. Histological changes were evaluated on slices stained with H&E, trichromic and PAS. Glycogen content was measured in liver samples. α-SMA and SREBP-1 immunopositive cells were identified in liver tissue. Results NASH was characterized by elevated triglycerides, elevated liver damage enzymes, and the presence of necrosis, inflammation, steatosis, and fibrosis. Significant amounts of glycogen were found, along with α-SMA positive cells in fibrosis areas. The over-expression of SREBP-1 in cytoplasm and nuclei was evident. Animals with NASH treated with β-HPC showed a significant reduction in inflammation, necrosis, and glycogen content in the liver. A reduction in α-SMA and SREBP-1 immunopositive cells correlated with a significant reduction in the degree of fibrosis and steatosis found in liver tissue. β-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with β-HPC did not show any alterations in liver enzyme function. Conclusions Our research shows that β-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting β-HPC could be potentially used in the treatment of NASH.https://doi.org/10.1186/s40360-022-00613-2Non-alcoholic steatohepatitisFibrosisSteatosisInflammationβ-hydroxyphosphocarnitine |
| spellingShingle | Janet Sánchez-Quevedo Emmanuel Ocampo-Rodríguez Elizabeth Alvarez-Ayala Anahí Rodríguez-López Miguel Angel Duarte-Vázquez Jorge Luis Rosado Lourdes Rodríguez-Fragoso β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats BMC Pharmacology and Toxicology Non-alcoholic steatohepatitis Fibrosis Steatosis Inflammation β-hydroxyphosphocarnitine |
| title | β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats |
| title_full | β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats |
| title_fullStr | β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats |
| title_full_unstemmed | β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats |
| title_short | β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats |
| title_sort | β hydroxyphosphocarnitine modifies fibrosis steatosis and improves liver function in non alcoholic steatohepatitis induced in rats |
| topic | Non-alcoholic steatohepatitis Fibrosis Steatosis Inflammation β-hydroxyphosphocarnitine |
| url | https://doi.org/10.1186/s40360-022-00613-2 |
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