Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats

Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing...

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Veröffentlicht in:Oxidative medicine and cellular longevity 2023, Vol.2023, p.9944985-11
Hauptverfasser: Sheweita, Salah A., Alian, Dalia M. Elsayed, Haroun, Medhat, Nounou, Mohamed Ismail, Patel, Ayyub, El-Khordagui, Labiba
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container_issue
container_start_page 9944985
container_title Oxidative medicine and cellular longevity
container_volume 2023
creator Sheweita, Salah A.
Alian, Dalia M. Elsayed
Haroun, Medhat
Nounou, Mohamed Ismail
Patel, Ayyub
El-Khordagui, Labiba
description Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) as in an indirect measure of free radicals. Interestingly, SF-CS NPs and T-SF-CS-NPs treatments significantly attenuated the inhibitory effects of SF on the activity of these enzymes whereas, GST activity was inhibited. Moreover, the protein expression of GST was downregulated upon treatment of rats with free SF, SF-CS-NPs, and T-SF CS-NPs. In contrast, the activity and protein expression of GPx was induced by SF-CS NPs and T-SF-CS-NPs treatments. The histopathological study showed that SF induced multiple adverse effects on the rat liver architecture which were markedly suppressed particularly by T-SF-CS NPs. In conclusion, chitosan nanoencapsulation of SF counteracted the adverse effects of SF on the activity of antioxidant enzymes and liver architecture. Findings might have significant implications in improving the safety and efficacy of SF treatment of the widely expanding disease conditions.
doi_str_mv 10.1155/2023/9944985
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Elsayed ; Haroun, Medhat ; Nounou, Mohamed Ismail ; Patel, Ayyub ; El-Khordagui, Labiba</creator><contributor>Selakovic, Dragica ; Dragica Selakovic</contributor><creatorcontrib>Sheweita, Salah A. ; Alian, Dalia M. Elsayed ; Haroun, Medhat ; Nounou, Mohamed Ismail ; Patel, Ayyub ; El-Khordagui, Labiba ; Selakovic, Dragica ; Dragica Selakovic</creatorcontrib><description>Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) as in an indirect measure of free radicals. Interestingly, SF-CS NPs and T-SF-CS-NPs treatments significantly attenuated the inhibitory effects of SF on the activity of these enzymes whereas, GST activity was inhibited. Moreover, the protein expression of GST was downregulated upon treatment of rats with free SF, SF-CS-NPs, and T-SF CS-NPs. In contrast, the activity and protein expression of GPx was induced by SF-CS NPs and T-SF-CS-NPs treatments. The histopathological study showed that SF induced multiple adverse effects on the rat liver architecture which were markedly suppressed particularly by T-SF-CS NPs. In conclusion, chitosan nanoencapsulation of SF counteracted the adverse effects of SF on the activity of antioxidant enzymes and liver architecture. Findings might have significant implications in improving the safety and efficacy of SF treatment of the widely expanding disease conditions.</description><identifier>ISSN: 1942-0900</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2023/9944985</identifier><identifier>PMID: 36891377</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Acids ; Animals ; Antioxidants ; Antioxidants - pharmacology ; Bioavailability ; Catalase - metabolism ; Chitosan - pharmacology ; Endangered &amp; extinct species ; Enzymes ; Erectile dysfunction ; Glutathione - metabolism ; Glutathione Peroxidase - metabolism ; Laboratory animals ; Liver ; Liver - metabolism ; Male ; Molecular weight ; Nanoparticles ; Nitric oxide ; Nitrogen dioxide ; Oxidative Stress ; Particle size ; Physical properties ; Potassium ; Protein expression ; Proteins ; Rats ; Sildenafil Citrate - metabolism ; Sildenafil Citrate - pharmacology ; Sildenafil Citrate - therapeutic use ; Sodium ; Superoxide Dismutase - metabolism</subject><ispartof>Oxidative medicine and cellular longevity, 2023, Vol.2023, p.9944985-11</ispartof><rights>Copyright © 2023 Salah A. Sheweita et al.</rights><rights>Copyright © 2023 Salah A. Sheweita et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2023 Salah A. 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Elsayed</au><au>Haroun, Medhat</au><au>Nounou, Mohamed Ismail</au><au>Patel, Ayyub</au><au>El-Khordagui, Labiba</au><au>Selakovic, Dragica</au><au>Dragica Selakovic</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats</atitle><jtitle>Oxidative medicine and cellular longevity</jtitle><addtitle>Oxid Med Cell Longev</addtitle><date>2023</date><risdate>2023</risdate><volume>2023</volume><spage>9944985</spage><epage>11</epage><pages>9944985-11</pages><issn>1942-0900</issn><eissn>1942-0994</eissn><abstract>Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) as in an indirect measure of free radicals. Interestingly, SF-CS NPs and T-SF-CS-NPs treatments significantly attenuated the inhibitory effects of SF on the activity of these enzymes whereas, GST activity was inhibited. Moreover, the protein expression of GST was downregulated upon treatment of rats with free SF, SF-CS-NPs, and T-SF CS-NPs. In contrast, the activity and protein expression of GPx was induced by SF-CS NPs and T-SF-CS-NPs treatments. The histopathological study showed that SF induced multiple adverse effects on the rat liver architecture which were markedly suppressed particularly by T-SF-CS NPs. In conclusion, chitosan nanoencapsulation of SF counteracted the adverse effects of SF on the activity of antioxidant enzymes and liver architecture. 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subjects Acids
Animals
Antioxidants
Antioxidants - pharmacology
Bioavailability
Catalase - metabolism
Chitosan - pharmacology
Endangered & extinct species
Enzymes
Erectile dysfunction
Glutathione - metabolism
Glutathione Peroxidase - metabolism
Laboratory animals
Liver
Liver - metabolism
Male
Molecular weight
Nanoparticles
Nitric oxide
Nitrogen dioxide
Oxidative Stress
Particle size
Physical properties
Potassium
Protein expression
Proteins
Rats
Sildenafil Citrate - metabolism
Sildenafil Citrate - pharmacology
Sildenafil Citrate - therapeutic use
Sodium
Superoxide Dismutase - metabolism
title Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats
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