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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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 & 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. Sheweita et al. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3635-3c70b535d43292c221ad0f60fc59956680b9655fcee6c8e635a729259a105a03</citedby><cites>FETCH-LOGICAL-c3635-3c70b535d43292c221ad0f60fc59956680b9655fcee6c8e635a729259a105a03</cites><orcidid>0000-0002-3511-7765 ; 0000-0001-8113-4403 ; 0000-0002-5320-3202 ; 0000-0002-6607-8113 ; 0000-0003-3814-8986 ; 0000-0002-8589-2700</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988388/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988388/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,4025,27928,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36891377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Selakovic, Dragica</contributor><contributor>Dragica Selakovic</contributor><creatorcontrib>Sheweita, Salah A.</creatorcontrib><creatorcontrib>Alian, Dalia M. Elsayed</creatorcontrib><creatorcontrib>Haroun, Medhat</creatorcontrib><creatorcontrib>Nounou, Mohamed Ismail</creatorcontrib><creatorcontrib>Patel, Ayyub</creatorcontrib><creatorcontrib>El-Khordagui, Labiba</creatorcontrib><title>Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats</title><title>Oxidative medicine and cellular longevity</title><addtitle>Oxid Med Cell Longev</addtitle><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><subject>Acids</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Bioavailability</subject><subject>Catalase - metabolism</subject><subject>Chitosan - pharmacology</subject><subject>Endangered & extinct species</subject><subject>Enzymes</subject><subject>Erectile dysfunction</subject><subject>Glutathione - metabolism</subject><subject>Glutathione Peroxidase - metabolism</subject><subject>Laboratory animals</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Molecular weight</subject><subject>Nanoparticles</subject><subject>Nitric oxide</subject><subject>Nitrogen dioxide</subject><subject>Oxidative Stress</subject><subject>Particle size</subject><subject>Physical properties</subject><subject>Potassium</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Rats</subject><subject>Sildenafil Citrate - metabolism</subject><subject>Sildenafil Citrate - pharmacology</subject><subject>Sildenafil Citrate - therapeutic use</subject><subject>Sodium</subject><subject>Superoxide Dismutase - metabolism</subject><issn>1942-0900</issn><issn>1942-0994</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kU9vEzEQxS0Eom3gxhlZ4oIEof6z3l1fkKIolEqFSrR3a-KdJS4bO9hOoP0OfOc6TYiAA5Ile-TfvJmnR8gLzt5xrtSpYEKeal1VulWPyDHXlRizUj8-vBk7Iicp3TBWS1Hxp-RI1q3msmmOya_pwuWQwNPP4MMKYnZ2wEQnw4AbBxk7mhdIJ90GY0I663u0OdHQ0ys3dOihdwMN_gG6_Ok6yG6D9CpHTIl-gvittFHwHZ347MIW8JnO_N3tsojaArvsyjjn6RfI6Rl50sOQ8Pn-HpHrD7Pr6cfxxeXZ-XRyMbaylmosbcPmSqqukkILKwSHjvU1663SWtV1y-a6Vqq3iLVtsbRAU0ClgTMFTI7I-53saj1fYmfR5wiDWUW3hHhrAjjz9493C_M1bIzWbSvLGZHXe4EYvq8xZbN0yeIwgMewTkY0reJaayYL-uof9Casoy_uCtWoSulKbjd6u6NsDClF7A_LcGa2MZttzGYfc8Ff_mngAP_OtQBvdsDC-Q5-uP_L3QPcm7ET</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Sheweita, Salah A.</creator><creator>Alian, Dalia M. 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Elsayed ; Haroun, Medhat ; Nounou, Mohamed Ismail ; Patel, Ayyub ; El-Khordagui, Labiba</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3635-3c70b535d43292c221ad0f60fc59956680b9655fcee6c8e635a729259a105a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acids</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Bioavailability</topic><topic>Catalase - metabolism</topic><topic>Chitosan - pharmacology</topic><topic>Endangered & extinct species</topic><topic>Enzymes</topic><topic>Erectile dysfunction</topic><topic>Glutathione - metabolism</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>Laboratory animals</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Molecular weight</topic><topic>Nanoparticles</topic><topic>Nitric oxide</topic><topic>Nitrogen dioxide</topic><topic>Oxidative Stress</topic><topic>Particle size</topic><topic>Physical properties</topic><topic>Potassium</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Rats</topic><topic>Sildenafil Citrate - metabolism</topic><topic>Sildenafil Citrate - pharmacology</topic><topic>Sildenafil Citrate - therapeutic use</topic><topic>Sodium</topic><topic>Superoxide Dismutase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sheweita, Salah A.</creatorcontrib><creatorcontrib>Alian, Dalia M. Elsayed</creatorcontrib><creatorcontrib>Haroun, Medhat</creatorcontrib><creatorcontrib>Nounou, Mohamed Ismail</creatorcontrib><creatorcontrib>Patel, Ayyub</creatorcontrib><creatorcontrib>El-Khordagui, Labiba</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oxidative medicine and cellular longevity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sheweita, Salah A.</au><au>Alian, Dalia M. 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. Findings might have significant implications in improving the safety and efficacy of SF treatment of the widely expanding disease conditions.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>36891377</pmid><doi>10.1155/2023/9944985</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3511-7765</orcidid><orcidid>https://orcid.org/0000-0001-8113-4403</orcidid><orcidid>https://orcid.org/0000-0002-5320-3202</orcidid><orcidid>https://orcid.org/0000-0002-6607-8113</orcidid><orcidid>https://orcid.org/0000-0003-3814-8986</orcidid><orcidid>https://orcid.org/0000-0002-8589-2700</orcidid><oa>free_for_read</oa></addata></record> |
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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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