Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis

Background: Cholestasis is a disorder of the formation or flow of bile. Among its contributors, tumour necrosis factor (TNF)-α stands out as the most influential inducer of apoptosis. Meanwhile, ursodeoxycholic acid (UDCA) is a valuable agent with choleretic properties, protecting the hepatobiliary...

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Main Authors: Danu Darmawan, Endang Sri Lestari, Sigit Adi Prasetyo, Muflihatul Muniroh, Agung Aji Prasetyo
Format: Article
Language:English
Published: Faculty of Medicine 2023-08-01
Series:JKKI (Jurnal Kedokteran dan Kesehatan Indonesia)
Online Access:https://jurnal.uii.ac.id/JKKI/article/view/28100
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author Danu Darmawan
Endang Sri Lestari
Sigit Adi Prasetyo
Muflihatul Muniroh
Agung Aji Prasetyo
author_facet Danu Darmawan
Endang Sri Lestari
Sigit Adi Prasetyo
Muflihatul Muniroh
Agung Aji Prasetyo
author_sort Danu Darmawan
collection DOAJ
description Background: Cholestasis is a disorder of the formation or flow of bile. Among its contributors, tumour necrosis factor (TNF)-α stands out as the most influential inducer of apoptosis. Meanwhile, ursodeoxycholic acid (UDCA) is a valuable agent with choleretic properties, protecting the hepatobiliary system. Glutathione (GSH) enhances endothelial response and prevents liver fibrosis Objectives: This study evaluates the effect of a combination of GSH-UDCA on splenic TNF-α expression and apoptosis index in Sprague Dawley (SD) rats with cholestasis Methods: This experiment with a post-tests-only control group design involving 28 male SD rats. They were randomly into four groups: group (K) with 20 mg UDCA, group 1 (P1) with 10 mg UDCA + 10 mg GSH, group 2 (P2) was given UDCA 20 mg + GSH 15 mg, and group 3 (P3) was given UDCA 30 mg + GSH 20 mg. Cholestasis was obtained by ligation of the common bile duct through a laparotomy. During three weeks of trial, rats were administered daily with UDCA orally and GSH intramuscularly. On day 22, rats were sacrificed and spleen samples were taken for anatomical pathology examination. Results: There were significant differences in TNF-α expression between groups K vs P3; P1 vs P3, and P2 vs P3 (p=0.002). There was a significant difference in the apoptotic index between groups K vs P1 (p<0.001); K vs P2 (p=0.004), and K vs P3 (p=0.005). Conclusions: The UDCA-GSH combination demonstrated a prophylactic effect in SD rats with cholestasis and might be an effective supplemental therapy with UDCA for cholestatic diseases. The difference in TNF-α expression and apoptotic index was lower in SD rats UDCA-glutathione combination group than single dose UDCA. Between TNF-α and the apoptotic index, there is a moderate positive relation.
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spelling doaj.art-8b9d815e80f847da8cac7cae1bc174b82023-09-21T04:54:28ZengFaculty of MedicineJKKI (Jurnal Kedokteran dan Kesehatan Indonesia)2085-41452527-29502023-08-0115316210.20885/JKKI.Vol14.Iss2.art637510Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasisDanu Darmawan0Endang Sri Lestari1https://orcid.org/0000-0002-6803-3453Sigit Adi Prasetyo2https://orcid.org/0000-0002-9595-0716Muflihatul Muniroh3https://orcid.org/0000-0003-0020-6722Agung Aji Prasetyo4General Surgery Resident, Faculty of Medicine Diponegoro University/Kariadi Central Hospital, Semarang, IndonesiaMicrobiology Department, Faculty of Medicine Diponegoro University/Kariadi Central Hospital, Semarang, IndonesiaDigestive Surgery Division, Surgery Department, Faculty of Medicine Diponegoro University / Kariadi Central Hospital, Semarang, IndonesiaPhysiology Department, Faculty of Medicine Diponegoro University / Kariadi Central Hospital, Semarang, IndonesiaPediatric Surgery Division, Surgery Department, Faculty of Medicine Diponegoro University / Kariadi Central Hospital, Semarang, IndonesiaBackground: Cholestasis is a disorder of the formation or flow of bile. Among its contributors, tumour necrosis factor (TNF)-α stands out as the most influential inducer of apoptosis. Meanwhile, ursodeoxycholic acid (UDCA) is a valuable agent with choleretic properties, protecting the hepatobiliary system. Glutathione (GSH) enhances endothelial response and prevents liver fibrosis Objectives: This study evaluates the effect of a combination of GSH-UDCA on splenic TNF-α expression and apoptosis index in Sprague Dawley (SD) rats with cholestasis Methods: This experiment with a post-tests-only control group design involving 28 male SD rats. They were randomly into four groups: group (K) with 20 mg UDCA, group 1 (P1) with 10 mg UDCA + 10 mg GSH, group 2 (P2) was given UDCA 20 mg + GSH 15 mg, and group 3 (P3) was given UDCA 30 mg + GSH 20 mg. Cholestasis was obtained by ligation of the common bile duct through a laparotomy. During three weeks of trial, rats were administered daily with UDCA orally and GSH intramuscularly. On day 22, rats were sacrificed and spleen samples were taken for anatomical pathology examination. Results: There were significant differences in TNF-α expression between groups K vs P3; P1 vs P3, and P2 vs P3 (p=0.002). There was a significant difference in the apoptotic index between groups K vs P1 (p<0.001); K vs P2 (p=0.004), and K vs P3 (p=0.005). Conclusions: The UDCA-GSH combination demonstrated a prophylactic effect in SD rats with cholestasis and might be an effective supplemental therapy with UDCA for cholestatic diseases. The difference in TNF-α expression and apoptotic index was lower in SD rats UDCA-glutathione combination group than single dose UDCA. Between TNF-α and the apoptotic index, there is a moderate positive relation.https://jurnal.uii.ac.id/JKKI/article/view/28100
spellingShingle Danu Darmawan
Endang Sri Lestari
Sigit Adi Prasetyo
Muflihatul Muniroh
Agung Aji Prasetyo
Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis
JKKI (Jurnal Kedokteran dan Kesehatan Indonesia)
title Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis
title_full Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis
title_fullStr Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis
title_full_unstemmed Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis
title_short Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis
title_sort effects of ursodeoxycholic acid and glutathione combination in spleen tnf α and apoptotic index in rats with cholestasis
url https://jurnal.uii.ac.id/JKKI/article/view/28100
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