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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Veröffentlicht in:Comparative clinical pathology 2024-04, Vol.33 (2), p.287-302
Hauptverfasser: Ajah, Obinna, Onyedikachi, Uchechi Bliss, Nkwocha, Callistus Chukwuebuka
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creator Ajah, Obinna
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Nkwocha, Callistus Chukwuebuka
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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Medical Complete (Alumni)</collection><collection>Nursing &amp; 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  &lt; 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  &lt; 0.05) higher than that of the control group. The UD-treated group (DOX + 300 mg/kg) showed a significant ( p  &lt; 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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