Bile acid synthesis in HepG2 cells: effect of cyclosporin

J, Levy; Budai, K; Javitt, Norman B.

doi:10.1016/s0022-2275(20)39774-1

Cited by 14 publications

(4 citation statements)

References 20 publications

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“…Chenodeoxycholic acid levels were detected in solvent controls and were diminished after CsA treatment, which suggests that CsA treatment inhibits the alternative bile acid biosynthesis. Previous studies showed a decreased activity of CYP27A1 after CsA exposure, resulting in a down-regulation of the alternative bile acid biosynthesis pathway [63][64] , which was confirmed in our study. CYP27A1 was significantly down-regulated after 20 µM CsA exposure for 48 and 72 hours with a FC of -1.76 and -2.2, respectively.…”

Section: Discussionsupporting

confidence: 91%

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In vitro toxicogenomics : unravelling the mechanisms underlying drug-induced hepatotoxicity

Hof¹

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Section: Discussionsupporting

confidence: 91%

“…62 The recent introduction and advances of next generation sequencing of RNA molecules has the potential to further improve the transcriptomic field, where sequencing can lead to the discovery of new transcripts involved in drug-induced toxicity. 63…”

Section: Transcriptomicsmentioning

confidence: 99%

In vitro toxicogenomics : unravelling the mechanisms underlying drug-induced hepatotoxicity

Hof¹

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“…The presence of BAs in the medium can stimulate BA synthesis itself [33][34][35]. Therefore, the medium supplemented with TUDCA (CTC and PTC, Figure 9B) may have stimulated BA production in the cells under detectable conditions (above both the LOD and LOQ of the method).…”

Section: Results Obtained For the Experimental Groupsmentioning

confidence: 99%

“…When the method is applied to the analyses of real samples, interfering species from the DMEM medium may be present, even after solid phase extraction, which may explain the higher proximity between the TUDCA and GCA peaks to the system signal (absent in the analytical standards analyses—Figure 7). The HepG2 cells are reportedly capable of synthesizing BAs [31–33]. However, no TUDCA concentrations were detected in the CON and PMT experimental groups (Figure 9A), which may be explained by the method's LOD 00 µmol/L.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of tauroursodeoxycholic acid in liver cells’ cultures by MEKC: Initial hints to comprehend its role in diabetes mellitus of obese individuals

Simões,

Muniz,

Araujo

et al. 2024

Electrophoresis

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Genetic factors, diet, lifestyle, and other factors lead to various complications in the body, such as obesity and other chronic diseases. The inflammatory state caused by excessive accumulation of body fat affects the pathways related to the control of glycemic homeostasis, leading to a high demand for insulin, to subsequent failure of stressed β cells, and development of type 2 diabetes mellitus (T2DM). The study of new endocrine signalers, such as bile acids (BAs), becomes necessary as it allows the development of alternatives for T2DM treatment. In this work, a methodology was developed to quantify tauroursodeoxycholic BA (TUDCA) in liver cells of the HepG2 strain treated in hyperlipidic medium. This BA helps to improve insulin clearance by increasing the expression of the insulin‐degrading enzyme, restoring sensitivity to this hormone, and making it viable for treating T2DM. Herein, a targeted metabolomic method for TUDCA determination in extracellular medium of hepatocyte matrices by micellar electrokinetic chromatography‐UV was optimized, validated, and applied. The optimized background electrolyte was composed of 40 mmol/L sodium cholate and 30 mmol/L sodium tetraborate at pH 9.0. The following figures of merit were evaluated: linearity, limit of quantification, limit of detection, accuracy, and precision. Data obtained with the validated electrophoretic method showed a self‐stimulation of TUDCA production in media supplemented only with BA. On the other hand, TUDCA concentration was reduced in the hyperlipidic medium. This suggests that, in these media, the effect of TUDCA is reduced, such as self‐stimulated production and consequent regulation of glycemic homeostasis. Therefore, the results reinforce the need for investigating TUDCA as a potential T2DM biomarker as well as its use to treat several comorbidities, such as obesity and diabetes mellitus.

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Cyclosporine A-Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation

et al. 2004

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Hyperlipidemia is a common side effect of cyclosporine A (CsA) after solid organ transplantation. CsA also markedly reduces the synthesis rate of bile salts in rats and can inhibit biliary bile salt secretion. It is not known, however, whether CsA inhibits the synthesis of bile salts in humans, and whether the hyperlipidemic effects of CsA are related to bile salt metabolism. Our objective was to assess the effects of CsA on the synthesis rate of bile salts and on plasma triglycerides and cholesterol levels in pediatric liver transplant patients. Before and after discontinuation of CsA treatment after liver transplantation, synthesis rate and pool size of the primary bile salts cholate and chenodeoxycholate were determined using a stable isotope dilution technique and related to plasma lipids. In 6 children (age: 3 -16 years) CsA treatment was discontinued at 2 years (median 2.3 years) after liver transplantation. Discontinuation of CsA increased synthesis rate of chenodeoxycholate (؉38%, P < .001) and cholate (؉21%, P < .05) and the pool size of chenodeoxycholate (؉54%, P < .001). Discontinuation of CsA decreased plasma levels of cholesterol ( -18%, P < .05) and triglycerides ( -23%, P < .05). Bile salt synthesis rate appeared to be inversely correlated with plasma cholesterol (Spearman rank correlation coefficient [r s ] ‫؍‬ -0.82, P < .01) and plasma triglyceride levels (r s ‫؍‬ -0.62, P < .05).

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Bile acid synthesis in HepG2 cells: effect of cyclosporin

Cited by 14 publications

References 20 publications

In vitro toxicogenomics : unravelling the mechanisms underlying drug-induced hepatotoxicity

In vitro toxicogenomics : unravelling the mechanisms underlying drug-induced hepatotoxicity

Evaluation of tauroursodeoxycholic acid in liver cells’ cultures by MEKC: Initial hints to comprehend its role in diabetes mellitus of obese individuals

Cyclosporine A-Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation

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