Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats
Background and Aim: Fipronil (FPN) is a potent pesticide that is heavily used around the world in agriculture. However, its irrational use could potentially have deleterious effects on animals and humans. The present study aimed to investigate the ability of sitagliptin (Sit) and losartan (LOS), whe...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Veterinary World
2021-07-01
|
| Series: | Veterinary World |
| Subjects: | |
| Online Access: | http://www.veterinaryworld.org/Vol.14/July-2021/25.pdf |
| _version_ | 1819088154153451520 |
|---|---|
| author | Sara T. Elazab Omar Samir Marwa E. Abass |
| author_facet | Sara T. Elazab Omar Samir Marwa E. Abass |
| author_sort | Sara T. Elazab |
| collection | DOAJ |
| description | Background and Aim: Fipronil (FPN) is a potent pesticide that is heavily used around the world in agriculture. However, its irrational use could potentially have deleterious effects on animals and humans. The present study aimed to investigate the ability of sitagliptin (Sit) and losartan (LOS), when used both individually or concurrently, to guard rat liver against the acute hepatotoxicity caused by FPN.
Materials and Methods: Forty-two adult male Wistar rats were equally divided into seven groups (6/group). Group I (control) received normal saline (0.5 mL/rat, vehicle for all treatments) by gavage once daily for 10 days. Group II received oral Sit (10 mg/kg body weight [BW]) daily for 10 days and Group III received oral LOS (5 mg/kg BW) daily for 10 days. Group IV received oral FPN (19.4 mg/kg BW; 1/5 of the oral LD50) for the past 5 days of the study. Groups V and VI received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) daily, respectively, 5 days prior and 5 days during FPN administration (19.4 mg/kg BW). Group VII received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) for 10 days with daily FPN during the past 5 days. After the end of the treatment period, the rats were humanely sacrificed and blood and liver tissue samples were collected for biochemical analysis and histopathological and immunohistochemical investigations.
Results: FPN administration resulted in elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase serum concentrations as well as increased malondialdehyde levels and reduced catalase, superoxide dismutase, glutathione peroxidase, and glutathione activity. The histopathological investigation showed disorganization of the hepatic cords and focal necrosis of the hepatocytes in FPN-intoxicated rats. Furthermore, the immunohistochemical examination showed that hepatic caspase-3 was overexpressed in the FPN-treated rats. The administration of Sit and LOS before and alongside FPN markedly mitigated the alterations caused by FPN and the hepatoprotective effects were more prominent in the combination group.
Conclusion: Sit and LOS, both individually or in combination, confers considerable hepatoprotection against FPN-induced hepatotoxicity. |
| first_indexed | 2024-12-21T21:47:31Z |
| format | Article |
| id | doaj.art-de89058b05164693b9e5ee689f98007e |
| institution | Directory Open Access Journal |
| issn | 0972-8988 2231-0916 |
| language | English |
| last_indexed | 2024-12-21T21:47:31Z |
| publishDate | 2021-07-01 |
| publisher | Veterinary World |
| record_format | Article |
| series | Veterinary World |
| spelling | doaj.art-de89058b05164693b9e5ee689f98007e2022-12-21T18:49:11ZengVeterinary WorldVeterinary World0972-89882231-09162021-07-011471901190710.14202/vetworld.2021.1901-1907Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in ratsSara T. Elazab0https://orcid.org/0000-0002-3348-7084Omar Samir1https://orcid.org/0000-0002-2022-5069Marwa E. Abass2Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura,35516, Egypt.Laboratory Animal Resource Center in Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.Department of Surgery, Anesthesiology and Radiology Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.Background and Aim: Fipronil (FPN) is a potent pesticide that is heavily used around the world in agriculture. However, its irrational use could potentially have deleterious effects on animals and humans. The present study aimed to investigate the ability of sitagliptin (Sit) and losartan (LOS), when used both individually or concurrently, to guard rat liver against the acute hepatotoxicity caused by FPN. Materials and Methods: Forty-two adult male Wistar rats were equally divided into seven groups (6/group). Group I (control) received normal saline (0.5 mL/rat, vehicle for all treatments) by gavage once daily for 10 days. Group II received oral Sit (10 mg/kg body weight [BW]) daily for 10 days and Group III received oral LOS (5 mg/kg BW) daily for 10 days. Group IV received oral FPN (19.4 mg/kg BW; 1/5 of the oral LD50) for the past 5 days of the study. Groups V and VI received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) daily, respectively, 5 days prior and 5 days during FPN administration (19.4 mg/kg BW). Group VII received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) for 10 days with daily FPN during the past 5 days. After the end of the treatment period, the rats were humanely sacrificed and blood and liver tissue samples were collected for biochemical analysis and histopathological and immunohistochemical investigations. Results: FPN administration resulted in elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase serum concentrations as well as increased malondialdehyde levels and reduced catalase, superoxide dismutase, glutathione peroxidase, and glutathione activity. The histopathological investigation showed disorganization of the hepatic cords and focal necrosis of the hepatocytes in FPN-intoxicated rats. Furthermore, the immunohistochemical examination showed that hepatic caspase-3 was overexpressed in the FPN-treated rats. The administration of Sit and LOS before and alongside FPN markedly mitigated the alterations caused by FPN and the hepatoprotective effects were more prominent in the combination group. Conclusion: Sit and LOS, both individually or in combination, confers considerable hepatoprotection against FPN-induced hepatotoxicity.http://www.veterinaryworld.org/Vol.14/July-2021/25.pdffipronilhepatotoxicitylosartanoxidative stresssitagliptin |
| spellingShingle | Sara T. Elazab Omar Samir Marwa E. Abass Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats Veterinary World fipronil hepatotoxicity losartan oxidative stress sitagliptin |
| title | Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats |
| title_full | Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats |
| title_fullStr | Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats |
| title_full_unstemmed | Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats |
| title_short | Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats |
| title_sort | synergistic effects of sitagliptin and losartan against fipronil induced hepatotoxicity in rats |
| topic | fipronil hepatotoxicity losartan oxidative stress sitagliptin |
| url | http://www.veterinaryworld.org/Vol.14/July-2021/25.pdf |
| work_keys_str_mv | AT saratelazab synergisticeffectsofsitagliptinandlosartanagainstfipronilinducedhepatotoxicityinrats AT omarsamir synergisticeffectsofsitagliptinandlosartanagainstfipronilinducedhepatotoxicityinrats AT marwaeabass synergisticeffectsofsitagliptinandlosartanagainstfipronilinducedhepatotoxicityinrats |