Tissue & cell · 2026
Olea europaea leaf extract mitigates doxorubicin-induced hepatotoxicity associated with modulation of oxidative stress, inflammation, and apoptosis: Integrated biochemical, molecular, and histopathological evidence.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ibrahim Mahrous A, Khalifa Athar M, Galhom Rania A, Shehata Shaimaa A
Аннотация
BACKGROUND: Doxorubicin (DOX) is an effective antineoplastic agent whose clinical use is limited by hepatotoxicity. This study evaluated the hepatoprotective effects of Olea europaea leaf extract (OLE) in a rat model of DOX -induced hepatotoxicity.
METHODS: Thirty-two male Wistar rats were randomly assigned to four groups: control, OLE (200 mg/kg/day by oral gavage for 20 days), DOX (20 mg/kg, single intraperitoneal injection), and DOX and OLE. Biochemical, histopathological, immunohistochemical, and qPCR analyses were performed to evaluate oxidative stress and antioxidant status, while molecular docking was used to investigate potential molecular interactions.
RESULTS: DOX induced hepatotoxicity, as evidenced by significant reductions in hepatic reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. It also significantly increased hepatic malondialdehyde (MDA) levels and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin concentrations, accompanied by marked histopathological alterations. Pretreatment with OLE significantly attenuated these changes by restoring antioxidant status, reducing oxidative stress, and improving liver histology. At the molecular level, OLE upregulated silent information regulator 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2), while downregulating forkhead box protein O1 (FOXO1), inducible nitric oxide synthase (iNOS), p53 and interleukin-6 (IL-6) compared with the DOX group. Molecular docking suggested potential interactions between OLE constituents and multiple proteins involved in oxidative stress and inflammatory pathways, providing computational support for the observed hepatoprotective effects.
CONCLUSION: OLE ameliorated DOX -induced hepatotoxicity by enhancing antioxidant defenses and suppressing inflammatory and apoptotic pathways, suggesting its potential as an adjuvant therapy to reduce DOX-induced liver toxicity.
METHODS: Thirty-two male Wistar rats were randomly assigned to four groups: control, OLE (200 mg/kg/day by oral gavage for 20 days), DOX (20 mg/kg, single intraperitoneal injection), and DOX and OLE. Biochemical, histopathological, immunohistochemical, and qPCR analyses were performed to evaluate oxidative stress and antioxidant status, while molecular docking was used to investigate potential molecular interactions.
RESULTS: DOX induced hepatotoxicity, as evidenced by significant reductions in hepatic reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. It also significantly increased hepatic malondialdehyde (MDA) levels and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin concentrations, accompanied by marked histopathological alterations. Pretreatment with OLE significantly attenuated these changes by restoring antioxidant status, reducing oxidative stress, and improving liver histology. At the molecular level, OLE upregulated silent information regulator 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2), while downregulating forkhead box protein O1 (FOXO1), inducible nitric oxide synthase (iNOS), p53 and interleukin-6 (IL-6) compared with the DOX group. Molecular docking suggested potential interactions between OLE constituents and multiple proteins involved in oxidative stress and inflammatory pathways, providing computational support for the observed hepatoprotective effects.
CONCLUSION: OLE ameliorated DOX -induced hepatotoxicity by enhancing antioxidant defenses and suppressing inflammatory and apoptotic pathways, suggesting its potential as an adjuvant therapy to reduce DOX-induced liver toxicity.