Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study
The therapeutic benefit of doxorubicin has led to a tremendous improvement in treating cancer. However, it has been associated with cardiotoxicity, renal, and hepatic toxicities, among others. Hence, the continuous search for natural scavengers of DOX-induced toxicity remains imperative. This study...
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description | The therapeutic benefit of doxorubicin has led to a tremendous improvement in treating cancer. However, it has been associated with cardiotoxicity, renal, and hepatic toxicities, among others. Hence, the continuous search for natural scavengers of DOX-induced toxicity remains imperative. This study evaluated the hepatoprotective and nephroprotective effects of ethanol extracts of
Urtica dioica
(UD) leaves on doxorubicin-induced oxidative stress. This study comprised 5 groups: control, doxorubicin (DOX: 15 mg/kg), UD-treated group (DOX + 300 mg/kg), a second UD-treated group (DOX + 600 mg/kg), and UD-treated group (600 mg/kg alone). The in vitro antioxidant potential of UD was assayed with FRAP and DPPH, and GCMS-identified UD phytoconstituents were docked against NADPH oxidase (2CDU) and nitric oxide synthase (2FLQ) using molecular docking tools such as Discovery Studio, Open Babel, and PyRX. UD had a concentration-dependent FRAP better than BHT and a DPPH scavenging activity of IC50 265.96 g/ml. The DOX group had hepatic and renal alteration that was evident in the significant (
p
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doi_str_mv | 10.1007/s00580-024-03550-0 |
format | Article |
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Urtica dioica
(UD) leaves on doxorubicin-induced oxidative stress. This study comprised 5 groups: control, doxorubicin (DOX: 15 mg/kg), UD-treated group (DOX + 300 mg/kg), a second UD-treated group (DOX + 600 mg/kg), and UD-treated group (600 mg/kg alone). The in vitro antioxidant potential of UD was assayed with FRAP and DPPH, and GCMS-identified UD phytoconstituents were docked against NADPH oxidase (2CDU) and nitric oxide synthase (2FLQ) using molecular docking tools such as Discovery Studio, Open Babel, and PyRX. UD had a concentration-dependent FRAP better than BHT and a DPPH scavenging activity of IC50 265.96 g/ml. The DOX group had hepatic and renal alteration that was evident in the significant (
p
< 0.05) elevation of hepatic (AST and ALT) and renal (BUN, creatinine, Na+) markers with reduced antioxidant markers (GPx, CAT, GSH). The CRP level of the DOX group was also significantly (
p
< 0.05) higher than that of the control group. The UD-treated group (DOX + 300 mg/kg) showed a significant (
p
< 0.05) reduction in the CRP, hepatic, and renal biomarkers, with a significant improvement in the activities of the antioxidant markers. The selected UD compounds showed good binding affinities against 2CDU and 2FLQ. Beta-Bissabolene (-9.2 and -8.0 kg/mol) and Alpha-Terpineol (-7.7 and -7.0 kg/mol) have higher binding affinities and good hydrogen interactions with 2FLQ and 2CDU, with acceptable drug-likeness properties.
Urtica dioica
extract and its compounds showed great potential for preventing DOX-induced hepatotoxicity and nephrotoxicity through modulation and reduction of biomarkers of cellular toxicity and enhancement of endogenous antioxidant enzymes. Beta-Bissabolene and Alpha-Terpineol from UD, through molecular docking, showed to be very potent in preventing ROS-mediated oxidative stress; hence, they may be adopted as toxicity-preventive candidates in doxorubicin treatments.</description><identifier>ISSN: 1618-565X</identifier><identifier>ISSN: 1618-5641</identifier><identifier>EISSN: 1618-565X</identifier><identifier>DOI: 10.1007/s00580-024-03550-0</identifier><language>eng</language><publisher>London: Springer London</publisher><subject>alpha-terpineol ; antioxidant activity ; Antioxidants ; Biomarkers ; Cardiotoxicity ; chemical constituents of plants ; Creatinine ; cytotoxicity ; Doxorubicin ; ethanol ; Hematology ; Hepatotoxicity ; hydrogen ; inhibitory concentration 50 ; Kidneys ; Liver ; Medicine ; Medicine & Public Health ; NAD(P)H oxidase ; NAD(P)H oxidase (H2O2-forming) ; nephroprotective effect ; nephrotoxicity ; Nitric-oxide synthase ; Oncology ; Original Article ; Oxidative stress ; Pathology ; Terpineol ; therapeutics ; Toxicity ; Urtica dioica</subject><ispartof>Comparative clinical pathology, 2024-04, Vol.33 (2), p.287-302</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2180-74d2792348e044064a7b853b8c6d97196f89dd2d89ff003be7e5e9e55a766c223</cites><orcidid>0000-0001-5716-7897 ; 0000-0003-4591-0318 ; 0000-0002-2845-3429</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00580-024-03550-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00580-024-03550-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Ajah, Obinna</creatorcontrib><creatorcontrib>Onyedikachi, Uchechi Bliss</creatorcontrib><creatorcontrib>Nkwocha, Callistus Chukwuebuka</creatorcontrib><title>Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study</title><title>Comparative clinical pathology</title><addtitle>Comp Clin Pathol</addtitle><description>The therapeutic benefit of doxorubicin has led to a tremendous improvement in treating cancer. However, it has been associated with cardiotoxicity, renal, and hepatic toxicities, among others. Hence, the continuous search for natural scavengers of DOX-induced toxicity remains imperative. This study evaluated the hepatoprotective and nephroprotective effects of ethanol extracts of
Urtica dioica
(UD) leaves on doxorubicin-induced oxidative stress. This study comprised 5 groups: control, doxorubicin (DOX: 15 mg/kg), UD-treated group (DOX + 300 mg/kg), a second UD-treated group (DOX + 600 mg/kg), and UD-treated group (600 mg/kg alone). The in vitro antioxidant potential of UD was assayed with FRAP and DPPH, and GCMS-identified UD phytoconstituents were docked against NADPH oxidase (2CDU) and nitric oxide synthase (2FLQ) using molecular docking tools such as Discovery Studio, Open Babel, and PyRX. UD had a concentration-dependent FRAP better than BHT and a DPPH scavenging activity of IC50 265.96 g/ml. The DOX group had hepatic and renal alteration that was evident in the significant (
p
< 0.05) elevation of hepatic (AST and ALT) and renal (BUN, creatinine, Na+) markers with reduced antioxidant markers (GPx, CAT, GSH). The CRP level of the DOX group was also significantly (
p
< 0.05) higher than that of the control group. The UD-treated group (DOX + 300 mg/kg) showed a significant (
p
< 0.05) reduction in the CRP, hepatic, and renal biomarkers, with a significant improvement in the activities of the antioxidant markers. The selected UD compounds showed good binding affinities against 2CDU and 2FLQ. Beta-Bissabolene (-9.2 and -8.0 kg/mol) and Alpha-Terpineol (-7.7 and -7.0 kg/mol) have higher binding affinities and good hydrogen interactions with 2FLQ and 2CDU, with acceptable drug-likeness properties.
Urtica dioica
extract and its compounds showed great potential for preventing DOX-induced hepatotoxicity and nephrotoxicity through modulation and reduction of biomarkers of cellular toxicity and enhancement of endogenous antioxidant enzymes. Beta-Bissabolene and Alpha-Terpineol from UD, through molecular docking, showed to be very potent in preventing ROS-mediated oxidative stress; hence, they may be adopted as toxicity-preventive candidates in doxorubicin treatments.</description><subject>alpha-terpineol</subject><subject>antioxidant activity</subject><subject>Antioxidants</subject><subject>Biomarkers</subject><subject>Cardiotoxicity</subject><subject>chemical constituents of plants</subject><subject>Creatinine</subject><subject>cytotoxicity</subject><subject>Doxorubicin</subject><subject>ethanol</subject><subject>Hematology</subject><subject>Hepatotoxicity</subject><subject>hydrogen</subject><subject>inhibitory concentration 50</subject><subject>Kidneys</subject><subject>Liver</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>NAD(P)H oxidase</subject><subject>NAD(P)H oxidase (H2O2-forming)</subject><subject>nephroprotective effect</subject><subject>nephrotoxicity</subject><subject>Nitric-oxide synthase</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Oxidative stress</subject><subject>Pathology</subject><subject>Terpineol</subject><subject>therapeutics</subject><subject>Toxicity</subject><subject>Urtica dioica</subject><issn>1618-565X</issn><issn>1618-5641</issn><issn>1618-565X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhSMEEmXgBVhZYsMm4H8n7FDFT6VK3VCJneXYNzMuiR1sZzTzcH03PJ1KRSzY-F4df-f6yqdp3hL8gWCsPmaMRYdbTHmLmRC1e9ZcEEm6Vkjx8_lf_cvmVc53GBPRMXbR3N-m4q1BzsdTgUNJxhY0--K3pkBGLh5iWgdvfWh9cKsFh3awmBJLPFS1HJEJDgVYdulJGo4or8uSIGcftqjKzhS_B5TLSXuwzNGtU1Xr_eCj3cFcN5hQfcRbyJ_QVUB7v4-P7AS20qnuY3-dLLms7vi6eTGaKcObx7ppbr9--XH5vb2--XZ1-fm6tZTUb1HcUdVTxjvAnGPJjRo6wYbOStcr0sux652jruvHEWM2gAIBPQhhlJSWUrZp3p_nLin-XiEXPftsYZpMgLhmzYhgSklKRUXf_YPexTWFup1mmHHBKSeyUvRM2RRzTjDqJfnZpKMmWJ8S1edEdU1UPyRaz03DzqZc4bCF9DT6P64_g5WpAQ</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Ajah, Obinna</creator><creator>Onyedikachi, Uchechi Bliss</creator><creator>Nkwocha, Callistus Chukwuebuka</creator><general>Springer London</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0001-5716-7897</orcidid><orcidid>https://orcid.org/0000-0003-4591-0318</orcidid><orcidid>https://orcid.org/0000-0002-2845-3429</orcidid></search><sort><creationdate>20240401</creationdate><title>Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study</title><author>Ajah, Obinna ; Onyedikachi, Uchechi Bliss ; Nkwocha, Callistus Chukwuebuka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2180-74d2792348e044064a7b853b8c6d97196f89dd2d89ff003be7e5e9e55a766c223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>alpha-terpineol</topic><topic>antioxidant activity</topic><topic>Antioxidants</topic><topic>Biomarkers</topic><topic>Cardiotoxicity</topic><topic>chemical constituents of plants</topic><topic>Creatinine</topic><topic>cytotoxicity</topic><topic>Doxorubicin</topic><topic>ethanol</topic><topic>Hematology</topic><topic>Hepatotoxicity</topic><topic>hydrogen</topic><topic>inhibitory concentration 50</topic><topic>Kidneys</topic><topic>Liver</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>NAD(P)H oxidase</topic><topic>NAD(P)H oxidase (H2O2-forming)</topic><topic>nephroprotective effect</topic><topic>nephrotoxicity</topic><topic>Nitric-oxide synthase</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Oxidative stress</topic><topic>Pathology</topic><topic>Terpineol</topic><topic>therapeutics</topic><topic>Toxicity</topic><topic>Urtica dioica</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ajah, Obinna</creatorcontrib><creatorcontrib>Onyedikachi, Uchechi Bliss</creatorcontrib><creatorcontrib>Nkwocha, Callistus Chukwuebuka</creatorcontrib><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Comparative clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ajah, Obinna</au><au>Onyedikachi, Uchechi Bliss</au><au>Nkwocha, Callistus Chukwuebuka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study</atitle><jtitle>Comparative clinical pathology</jtitle><stitle>Comp Clin Pathol</stitle><date>2024-04-01</date><risdate>2024</risdate><volume>33</volume><issue>2</issue><spage>287</spage><epage>302</epage><pages>287-302</pages><issn>1618-565X</issn><issn>1618-5641</issn><eissn>1618-565X</eissn><abstract>The therapeutic benefit of doxorubicin has led to a tremendous improvement in treating cancer. However, it has been associated with cardiotoxicity, renal, and hepatic toxicities, among others. Hence, the continuous search for natural scavengers of DOX-induced toxicity remains imperative. This study evaluated the hepatoprotective and nephroprotective effects of ethanol extracts of
Urtica dioica
(UD) leaves on doxorubicin-induced oxidative stress. This study comprised 5 groups: control, doxorubicin (DOX: 15 mg/kg), UD-treated group (DOX + 300 mg/kg), a second UD-treated group (DOX + 600 mg/kg), and UD-treated group (600 mg/kg alone). The in vitro antioxidant potential of UD was assayed with FRAP and DPPH, and GCMS-identified UD phytoconstituents were docked against NADPH oxidase (2CDU) and nitric oxide synthase (2FLQ) using molecular docking tools such as Discovery Studio, Open Babel, and PyRX. UD had a concentration-dependent FRAP better than BHT and a DPPH scavenging activity of IC50 265.96 g/ml. The DOX group had hepatic and renal alteration that was evident in the significant (
p
< 0.05) elevation of hepatic (AST and ALT) and renal (BUN, creatinine, Na+) markers with reduced antioxidant markers (GPx, CAT, GSH). The CRP level of the DOX group was also significantly (
p
< 0.05) higher than that of the control group. The UD-treated group (DOX + 300 mg/kg) showed a significant (
p
< 0.05) reduction in the CRP, hepatic, and renal biomarkers, with a significant improvement in the activities of the antioxidant markers. The selected UD compounds showed good binding affinities against 2CDU and 2FLQ. Beta-Bissabolene (-9.2 and -8.0 kg/mol) and Alpha-Terpineol (-7.7 and -7.0 kg/mol) have higher binding affinities and good hydrogen interactions with 2FLQ and 2CDU, with acceptable drug-likeness properties.
Urtica dioica
extract and its compounds showed great potential for preventing DOX-induced hepatotoxicity and nephrotoxicity through modulation and reduction of biomarkers of cellular toxicity and enhancement of endogenous antioxidant enzymes. Beta-Bissabolene and Alpha-Terpineol from UD, through molecular docking, showed to be very potent in preventing ROS-mediated oxidative stress; hence, they may be adopted as toxicity-preventive candidates in doxorubicin treatments.</abstract><cop>London</cop><pub>Springer London</pub><doi>10.1007/s00580-024-03550-0</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-5716-7897</orcidid><orcidid>https://orcid.org/0000-0003-4591-0318</orcidid><orcidid>https://orcid.org/0000-0002-2845-3429</orcidid></addata></record> |
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subjects | alpha-terpineol antioxidant activity Antioxidants Biomarkers Cardiotoxicity chemical constituents of plants Creatinine cytotoxicity Doxorubicin ethanol Hematology Hepatotoxicity hydrogen inhibitory concentration 50 Kidneys Liver Medicine Medicine & Public Health NAD(P)H oxidase NAD(P)H oxidase (H2O2-forming) nephroprotective effect nephrotoxicity Nitric-oxide synthase Oncology Original Article Oxidative stress Pathology Terpineol therapeutics Toxicity Urtica dioica |
title | Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study |
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