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Comparative Clinical Pathology

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20.02.2024 | Original Article

Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study

verfasst von: Obinna Ajah, Uchechi Bliss Onyedikachi, Callistus Chukwuebuka Nkwocha

Erschienen in: Comparative Clinical Pathology | Ausgabe 2/2024

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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.

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Titel: Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study
verfasst von: Obinna Ajah
Uchechi Bliss Onyedikachi
Callistus Chukwuebuka Nkwocha
Publikationsdatum: 20.02.2024
Verlag: Springer London
Erschienen in: Comparative Clinical Pathology / Ausgabe 2/2024
Print ISSN: 1618-5641
Elektronische ISSN: 1618-565X
DOI: https://doi.org/10.1007/s00580-024-03550-0

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Urtica dioica extract mitigates doxorubicin-induced hepatotoxicity and nephrotoxicity by suppressing oxidative stress and modulating biochemical indices: In vivo and molecular docking study

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

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