Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats
Cholestasis is a hepatobiliary condition that manifests as acute or chronic and results from disruptions in the bile flow, formation, or secretion processes. The Farnesoid X receptor (FXR) is a vital target for the therapy of cholestasis since it regulates BA homeostasis. Despite the discovery of mu...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Current Research in Pharmacology and Drug Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S259025712400004X |
| _version_ | 1797338198172499968 |
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| author | Doaa Adnan Atshan Munaf Hashim Zalzala |
| author_facet | Doaa Adnan Atshan Munaf Hashim Zalzala |
| author_sort | Doaa Adnan Atshan |
| collection | DOAJ |
| description | Cholestasis is a hepatobiliary condition that manifests as acute or chronic and results from disruptions in the bile flow, formation, or secretion processes. The Farnesoid X receptor (FXR) is a vital target for the therapy of cholestasis since it regulates BA homeostasis. Despite the discovery of multiple active FXR agonists, there are still no effective treatments for cholestasis. Papaverine is identified as an FXR agonist.This study investigates papaverine's efficacy and probable mechanism in protecting against alpha naphthylisothiocyanate (ANIT) induced cholestasis. Thirty male albino rats were divided into three groups, each with ten rats. Group I (control) rats were administered 1 mL/kg corn oil 48 h before sacrifice; group II rats were orally administered 100 mg/kg ANIT. Group III received a 200 mg/kg dosage of papaverine over seven consecutive days. A single dose of ANIT at a concentration of 100 mg/kg was orally administered on the fifth day; group II and III animals were euthanized 48 h after inducing cholestasis, and serum concentrations of liver function tests and total bile acid (TBA) were measured. Besides measuring the inflammatory mediator's tumor necrosis factor-alpha (TNF-α) and interleukin 1 (IL-1β), antioxidant markers such as superoxide dismutase (SOD) and glutathione (GSH) were also assessed. The findings indicated the enhancement in the liver function test and total bile acids, as well as in liver histology; papaverine significantly lowered TNF-α and IL-1β while SOD and GSH significantly increased. Additionally, papaverine upregulates Fxr gene expression, bile salt export pump (Besp), small heterodimer partner (shp), hepatocyte nuclear factor 1α (Hnfα), nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase (Ho-1), NAD(P)H quinone oxidoreductase 1 (Nqo1). Furthermore, papaverine increased protein expressions of Sirtuin1.(SIRT 1), FXR, HO-1, and BSEP levels in the rats' livers. The protective effects of papaverine may be attributed to the activation of FXR signaling pathways. These findings revealed that papaverine protects against ANIT-induced Cholestasis. |
| first_indexed | 2024-03-08T09:27:31Z |
| format | Article |
| id | doaj.art-0c5a9aea5bce418587fe953514325f82 |
| institution | Directory Open Access Journal |
| issn | 2590-2571 |
| language | English |
| last_indexed | 2024-03-08T09:27:31Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Pharmacology and Drug Discovery |
| spelling | doaj.art-0c5a9aea5bce418587fe953514325f822024-01-31T05:45:34ZengElsevierCurrent Research in Pharmacology and Drug Discovery2590-25712024-01-016100177Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in ratsDoaa Adnan Atshan0Munaf Hashim Zalzala1Ministry Of Health And Environment, Alnuman Teaching Hospital, Baghdad, IraqUniversity of Baghdad, College of Pharmacy, Department of Pharmacology and Toxicology, Baghdad, Iraq; Corresponding author.Cholestasis is a hepatobiliary condition that manifests as acute or chronic and results from disruptions in the bile flow, formation, or secretion processes. The Farnesoid X receptor (FXR) is a vital target for the therapy of cholestasis since it regulates BA homeostasis. Despite the discovery of multiple active FXR agonists, there are still no effective treatments for cholestasis. Papaverine is identified as an FXR agonist.This study investigates papaverine's efficacy and probable mechanism in protecting against alpha naphthylisothiocyanate (ANIT) induced cholestasis. Thirty male albino rats were divided into three groups, each with ten rats. Group I (control) rats were administered 1 mL/kg corn oil 48 h before sacrifice; group II rats were orally administered 100 mg/kg ANIT. Group III received a 200 mg/kg dosage of papaverine over seven consecutive days. A single dose of ANIT at a concentration of 100 mg/kg was orally administered on the fifth day; group II and III animals were euthanized 48 h after inducing cholestasis, and serum concentrations of liver function tests and total bile acid (TBA) were measured. Besides measuring the inflammatory mediator's tumor necrosis factor-alpha (TNF-α) and interleukin 1 (IL-1β), antioxidant markers such as superoxide dismutase (SOD) and glutathione (GSH) were also assessed. The findings indicated the enhancement in the liver function test and total bile acids, as well as in liver histology; papaverine significantly lowered TNF-α and IL-1β while SOD and GSH significantly increased. Additionally, papaverine upregulates Fxr gene expression, bile salt export pump (Besp), small heterodimer partner (shp), hepatocyte nuclear factor 1α (Hnfα), nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase (Ho-1), NAD(P)H quinone oxidoreductase 1 (Nqo1). Furthermore, papaverine increased protein expressions of Sirtuin1.(SIRT 1), FXR, HO-1, and BSEP levels in the rats' livers. The protective effects of papaverine may be attributed to the activation of FXR signaling pathways. These findings revealed that papaverine protects against ANIT-induced Cholestasis.http://www.sciencedirect.com/science/article/pii/S259025712400004XPapaverine effectANITCholestasisFXRInflammationLiver injury |
| spellingShingle | Doaa Adnan Atshan Munaf Hashim Zalzala Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats Current Research in Pharmacology and Drug Discovery Papaverine effect ANIT Cholestasis FXR Inflammation Liver injury |
| title | Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats |
| title_full | Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats |
| title_fullStr | Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats |
| title_full_unstemmed | Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats |
| title_short | Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats |
| title_sort | papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats |
| topic | Papaverine effect ANIT Cholestasis FXR Inflammation Liver injury |
| url | http://www.sciencedirect.com/science/article/pii/S259025712400004X |
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