Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats
Incidence of hepatotoxicity caused by the broad spectrum antibiotic combination amoxicillin-clavulanic acid (Co-amoxyclav) has been increasingly recognized and the mechanism of this toxicity remains undefined. On the other hand, Ursodeoxycholic acid (UDCA) has been suggested as efficient antioxidant...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-04-01
|
| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119317922 |
| _version_ | 1818588272873439232 |
|---|---|
| author | Gamal A. El-Sherbiny Ashraf Taye Ihab T. Abdel-Raheem |
| author_facet | Gamal A. El-Sherbiny Ashraf Taye Ihab T. Abdel-Raheem |
| author_sort | Gamal A. El-Sherbiny |
| collection | DOAJ |
| description | Incidence of hepatotoxicity caused by the broad spectrum antibiotic combination amoxicillin-clavulanic acid (Co-amoxyclav) has been increasingly recognized and the mechanism of this toxicity remains undefined. On the other hand, Ursodeoxycholic acid (UDCA) has been suggested as efficient antioxidant therapy in various liver diseases. Therefore, the present study was designed to elucidate the possible role of oxidative stress in hepatotoxicity induced by Co-amoxyclav and the putative protective role of UDCA in rats. Effects of amoxicillin (Amox; 50 mg/kg, orally, 21 d) or clavulanic acid (Clav; 10 mg/kg, orally, 21 d) and their combined administration on the biochemical liver parameters, reduced glutathione (GSH), lipid peroxidation measured as hepatic malondialdehyde (MDA) levels. In addition, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) production in liver homogenate were also evaluated. On the other hand, the protective effects of pretreatment with UDCA (20 mg/kg, orally, 21 d) on these parameters were also evaluated. Our results show that pretreatment with UDCA reduced the liver parameters that were enhanced by single or combined administration of Amox and/or Clav such as serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum bilirubin levels. Moreover, pretreatment with UDCA normalized the GSH level and inhibited the elevation in hepatic MDA concentration. The enhanced MPO activity and ROS production in liver homogenate of rats treated with Clav or Co-amoxyclav were also normalized by UDCA pretreatment. In conclusion, the present data suggest that UDCA acts as effective hepatoprotective agent against liver dysfunction caused by Co-amoxyclav and this effect is related to its antioxidant properties. |
| first_indexed | 2024-12-16T09:22:07Z |
| format | Article |
| id | doaj.art-8938c42b11c74b628172b53381d569e5 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-16T09:22:07Z |
| publishDate | 2009-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-8938c42b11c74b628172b53381d569e52022-12-21T22:36:45ZengElsevierAnnals of Hepatology1665-26812009-04-0182134140Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in ratsGamal A. El-Sherbiny0Ashraf Taye1Ihab T. Abdel-Raheem2Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University. EgyptDepartments of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, EgyptDepartment of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt; Address for correspondence:Incidence of hepatotoxicity caused by the broad spectrum antibiotic combination amoxicillin-clavulanic acid (Co-amoxyclav) has been increasingly recognized and the mechanism of this toxicity remains undefined. On the other hand, Ursodeoxycholic acid (UDCA) has been suggested as efficient antioxidant therapy in various liver diseases. Therefore, the present study was designed to elucidate the possible role of oxidative stress in hepatotoxicity induced by Co-amoxyclav and the putative protective role of UDCA in rats. Effects of amoxicillin (Amox; 50 mg/kg, orally, 21 d) or clavulanic acid (Clav; 10 mg/kg, orally, 21 d) and their combined administration on the biochemical liver parameters, reduced glutathione (GSH), lipid peroxidation measured as hepatic malondialdehyde (MDA) levels. In addition, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) production in liver homogenate were also evaluated. On the other hand, the protective effects of pretreatment with UDCA (20 mg/kg, orally, 21 d) on these parameters were also evaluated. Our results show that pretreatment with UDCA reduced the liver parameters that were enhanced by single or combined administration of Amox and/or Clav such as serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum bilirubin levels. Moreover, pretreatment with UDCA normalized the GSH level and inhibited the elevation in hepatic MDA concentration. The enhanced MPO activity and ROS production in liver homogenate of rats treated with Clav or Co-amoxyclav were also normalized by UDCA pretreatment. In conclusion, the present data suggest that UDCA acts as effective hepatoprotective agent against liver dysfunction caused by Co-amoxyclav and this effect is related to its antioxidant properties.http://www.sciencedirect.com/science/article/pii/S1665268119317922Ursodeoxycholic acidamoxicillinclavulanic acidhepatotoxicityoxidative stress. |
| spellingShingle | Gamal A. El-Sherbiny Ashraf Taye Ihab T. Abdel-Raheem Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats Annals of Hepatology Ursodeoxycholic acid amoxicillin clavulanic acid hepatotoxicity oxidative stress. |
| title | Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats |
| title_full | Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats |
| title_fullStr | Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats |
| title_full_unstemmed | Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats |
| title_short | Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats |
| title_sort | role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin clavulanic acid in rats |
| topic | Ursodeoxycholic acid amoxicillin clavulanic acid hepatotoxicity oxidative stress. |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119317922 |
| work_keys_str_mv | AT gamalaelsherbiny roleofursodeoxycholicacidinpreventionofhepatotoxicitycausedbyamoxicillinclavulanicacidinrats AT ashraftaye roleofursodeoxycholicacidinpreventionofhepatotoxicitycausedbyamoxicillinclavulanicacidinrats AT ihabtabdelraheem roleofursodeoxycholicacidinpreventionofhepatotoxicitycausedbyamoxicillinclavulanicacidinrats |