Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in Mice
Background and purpose: Amikacin (AMK) is a commonly used aminoglycoside antibiotic with rapid onset of action, low cost, and high antibacterial efficacy. However, its long-term use has been associated with kidney toxicity, which is a significant concern for patients. Hence, the present study was de...
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| Format: | Article |
| Language: | English |
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Mazandaran University of Medical Sciences
2023-10-01
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| Series: | Journal of Mazandaran University of Medical Sciences |
| Subjects: | |
| Online Access: | http://jmums.mazums.ac.ir/article-1-17906-en.pdf |
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| author | Mohammad Shokati Sayad Zahra Ramezanpour Fereshteh Talebpour Amiri Sholeh Akbari Maloos Naderi Fatemeh Shaki |
| author_facet | Mohammad Shokati Sayad Zahra Ramezanpour Fereshteh Talebpour Amiri Sholeh Akbari Maloos Naderi Fatemeh Shaki |
| author_sort | Mohammad Shokati Sayad |
| collection | DOAJ |
| description | Background and purpose: Amikacin (AMK) is a commonly used aminoglycoside antibiotic with rapid onset of action, low cost, and high antibacterial efficacy. However, its long-term use has been associated with kidney toxicity, which is a significant concern for patients. Hence, the present study was designed to evaluate the protective effect of pentoxifylline (PTX) against amikacin-induced nephrotoxicity in male mice.
Materials and methods: Forty-two Balb/c mice were allocated to seven groups as follows: I, control; II, AMK (500 mg/kg/day); III to V, received AMK plus PTX (50,100,200 mg/kg/day); VI, AMK plus vitamin C (500 mg/kg/day); and VII, PTX alone (200 mg/kg). All the treatment was done intraperitoneally for 15 consecutive days. Then, kidney tissues were separated and several factors including level of reactive oxygen species (ROS), protein carbonyl (PrC), lipid peroxidation (LPO), antioxidant content (glutathione), nitric oxide (NO) production, and expression of apoptosis-related genes (Bax and Bcl-2) were evaluated. Also, evaluation of biochemical parameters (BUN and Cr) as well as histopathological changes were performed.
Results: Administration of AMK led to significant changes in tissue pathology and the level of BUN and Cr. AMK significantly promoted ROS, LPO, PrC, and NO levels in kidney while it reduced GSH storage. Also, AMK injection led to significant increase in Bax/Bcl2 expression ratio. PTX alleviated oxidative stress markers and nitric oxide induced by AMK in kidney tissue. Moreover, AMK recovered biochemical and pathological changes associated with AMK. PTX treatment decreased the Bax expression and increased the expression of Bcl-2 significantly.
Conclusion: Pentoxifylline showed protective effects against amikacin-induced nephrotoxicity which may be attributed to its antioxidant activity and anti-apoptotic effects. So, it can be considered as a therapeutic approach against toxic effects of amikacin in kidney tissue. |
| first_indexed | 2024-03-10T13:33:06Z |
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| id | doaj.art-9a46a3b12bd44a35995add4d521eb2fb |
| institution | Directory Open Access Journal |
| issn | 1735-9260 1735-9279 |
| language | English |
| last_indexed | 2024-03-10T13:33:06Z |
| publishDate | 2023-10-01 |
| publisher | Mazandaran University of Medical Sciences |
| record_format | Article |
| series | Journal of Mazandaran University of Medical Sciences |
| spelling | doaj.art-9a46a3b12bd44a35995add4d521eb2fb2023-11-21T07:44:49ZengMazandaran University of Medical SciencesJournal of Mazandaran University of Medical Sciences1735-92601735-92792023-10-0133225115Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in MiceMohammad Shokati Sayad0Zahra Ramezanpour1Fereshteh Talebpour Amiri2Sholeh Akbari3Maloos Naderi4Fatemeh Shaki5 PhD Candidate of Toxicology, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran Student of Pharmacy, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran Associate professor, Department of Anatomy, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran PhD Candidate of Toxicology, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran PhD Candidate of Toxicology, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran Associate professor, Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran . Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran . The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran Background and purpose: Amikacin (AMK) is a commonly used aminoglycoside antibiotic with rapid onset of action, low cost, and high antibacterial efficacy. However, its long-term use has been associated with kidney toxicity, which is a significant concern for patients. Hence, the present study was designed to evaluate the protective effect of pentoxifylline (PTX) against amikacin-induced nephrotoxicity in male mice. Materials and methods: Forty-two Balb/c mice were allocated to seven groups as follows: I, control; II, AMK (500 mg/kg/day); III to V, received AMK plus PTX (50,100,200 mg/kg/day); VI, AMK plus vitamin C (500 mg/kg/day); and VII, PTX alone (200 mg/kg). All the treatment was done intraperitoneally for 15 consecutive days. Then, kidney tissues were separated and several factors including level of reactive oxygen species (ROS), protein carbonyl (PrC), lipid peroxidation (LPO), antioxidant content (glutathione), nitric oxide (NO) production, and expression of apoptosis-related genes (Bax and Bcl-2) were evaluated. Also, evaluation of biochemical parameters (BUN and Cr) as well as histopathological changes were performed. Results: Administration of AMK led to significant changes in tissue pathology and the level of BUN and Cr. AMK significantly promoted ROS, LPO, PrC, and NO levels in kidney while it reduced GSH storage. Also, AMK injection led to significant increase in Bax/Bcl2 expression ratio. PTX alleviated oxidative stress markers and nitric oxide induced by AMK in kidney tissue. Moreover, AMK recovered biochemical and pathological changes associated with AMK. PTX treatment decreased the Bax expression and increased the expression of Bcl-2 significantly. Conclusion: Pentoxifylline showed protective effects against amikacin-induced nephrotoxicity which may be attributed to its antioxidant activity and anti-apoptotic effects. So, it can be considered as a therapeutic approach against toxic effects of amikacin in kidney tissue.http://jmums.mazums.ac.ir/article-1-17906-en.pdfamikacinpentoxifyllinerenal toxicityoxidative damageapoptosis |
| spellingShingle | Mohammad Shokati Sayad Zahra Ramezanpour Fereshteh Talebpour Amiri Sholeh Akbari Maloos Naderi Fatemeh Shaki Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in Mice Journal of Mazandaran University of Medical Sciences amikacin pentoxifylline renal toxicity oxidative damage apoptosis |
| title | Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in Mice |
| title_full | Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in Mice |
| title_fullStr | Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in Mice |
| title_full_unstemmed | Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in Mice |
| title_short | Protective Effect of Pentoxifylline on Amikacin-Induced Renal Toxicity in Mice |
| title_sort | protective effect of pentoxifylline on amikacin induced renal toxicity in mice |
| topic | amikacin pentoxifylline renal toxicity oxidative damage apoptosis |
| url | http://jmums.mazums.ac.ir/article-1-17906-en.pdf |
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