Geraniol activates Nrf-2/HO-1 signaling pathway mediating protection against oxidative stress-induced apoptosis in hepatic ischemia-reperfusion injury

El-Emam, Soad Z.; Soubh, Ayman A.; Al-Mokaddem, Asmaa K.; El-Ella, Dina Moustafa Abo

doi:10.1007/s00210-020-01887-1

Cited by 32 publications

(26 citation statements)

References 64 publications

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“…Therefore, the observed induction of antioxidant enzymes by Ger could be explained, at least in part, by the functional activation of the Nrf2/HO-1 signaling pathway in the kidneys of MTX-induced rats. The role of Nrf2 in mediating the anti-inflammatory and antiapoptotic efficacies of Ger in MTX-administered rats was supported by previous reports, which demonstrated increased expression of Nrf2 and suppressed inflammation in hepatic ischemia-reperfusion injury [40], diet-induced experimental atherosclerosis [41] and in ovalbumin-induced allergic asthma [18].…”

Section: Ger and Oxidative Stress Parameters And Pathwayssupporting

confidence: 65%

“…Given its dual ability to attenuate oxidative injury and inflammation, geraniol administration prior to MTX prevented apoptotic signaling induced by MTX as shown by the diminished Bax and caspases and upregulation of the antiapoptotic Bcl2. In the same context, previous studies have shown that Ger suppressed apoptosis in LPS-induced acute lung injury [44], hepatic ischemia-reperfusion injury [40], isoproterenol-induced cardiotoxicity [12], traumatic injury of the spinal cord [35], chronic MPTP/probenecid-induced Parkinson's disease [45] and others.…”

Section: Ger and Apoptotic Signalingmentioning

confidence: 90%

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Geraniol Averts Methotrexate-Induced Acute Kidney Injury via Keap1/Nrf2/HO-1 and MAPK/NF-κB Pathways

Younis

Elsewedy

Shehata

et al. 2021

CIMB

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Objectives: Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways. Methods: Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg). Results: Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1β, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues. Conclusion: The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury.

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Section: Ger and Oxidative Stress Parameters And Pathwayssupporting

confidence: 65%

Section: Ger and Apoptotic Signalingmentioning

confidence: 90%

Geraniol Averts Methotrexate-Induced Acute Kidney Injury via Keap1/Nrf2/HO-1 and MAPK/NF-κB Pathways

Younis

Elsewedy

Shehata

et al. 2021

CIMB

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“…This effect was associated with various molecular mechanisms, such as increasing the TAC and GSH levels, decreasing MDA levels, activation of Nrf2, as well as the upregulation of HO-1 expression. In the same years, El-Emam et al [111] confirmed this result. The authors reported that oral administration of geraniol 100 and 200 mg/kg exhibited a protective effect against isoproterenol-induced cardiotoxicity by decreasing Keap1 expression and increasing nuclear accumulation of Nrf2.…”

Section: Shata and Eldebakymentioning

confidence: 74%

“…Terpenoids are volatile compounds that have various biological proprieties, such as antioxidant activity. Indeed, more than 20 works (Table 3) studied this effect in vivo [92][93][94][95][96][97][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126].…”

Section: Terpenoidsmentioning

confidence: 99%

Preclinical and Clinical Antioxidant Effects of Natural Compounds against Oxidative Stress-Induced Epigenetic Instability in Tumor Cells

et al. 2021

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ROS (reactive oxygen species) are produced via the noncomplete reduction in molecular oxygen in the mitochondria of higher organisms. The produced ROS are placed in various cell compartments, such as the mitochondria, cytoplasm, and endoplasmic reticulum. In general, there is an equilibrium between the synthesis of ROS and their reduction by the natural antioxidant defense system, called the redox system. Therefore, when this balance is upset, the excess ROS production can affect different macromolecules, such as proteins, lipids, nucleic acids, and sugars, which can lead to an electronic imbalance than oxidation of these macromolecules. Recently, it has also been shown that ROS produced at the cellular level can affect different signaling pathways that participate in the stimulation of transcription factors linked to cell proliferation and, consequently, to the carcinogenesis process. Indeed, ROS can activate the pathway of tyrosine kinase, MAP kinase, IKK, NF-KB, phosphoinositol 3 phosphate, and hypoxia-inducible factor (HIF). The activation of these signaling pathways directly contributes to the accelerated proliferation process and, as a result, the appearance of cancer. In addition, the use of antioxidants, especially natural ones, is now a major issue in the approach to cancer prevention. Some natural molecules, especially phytochemicals isolated from medicinal plants, have now shown interesting preclinical and clinical results.

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“…Geraniol has also been reported to induce activation of nuclear factor erythroid 2-related factor 2 (Nrf2). As upon oxidative stress, Nrf2 detaches from its cytoplasmic inhibitor protein and transfers into the nucleus to activate various antioxidant enzymes (e.g., glutathione peroxidase and superoxide dismutase), the activation of the Nrf2 pathway could be involved in the maintenance of the cellular defense mechanism through antioxidant properties [ 64 ]. Furthermore, previous studies have demonstrated that the administration of essential oil of Rosa damascena Mill L., whose major constituents are citronellol (38.04%) and geraniol (26.32%), promotes moderate inhibition of MDA production and increase in SOD activity in injured brain tissue [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Cymbopogon winterianus Essential Oil Attenuates Bleomycin-Induced Pulmonary Fibrosis in a Murine Model

et al. 2021

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The essential oil of Cymbopogon winterianus (EOCW) is a natural product with antioxidant, anti-inflammatory, and antifibrotic properties. We studied the effect of EOCW in the progression of histological changes of pulmonary fibrosis (PF) in a rodent model. The oil was obtained by hydrodistillation and characterized using gas chromatography–mass spectrometry. Intratracheal instillation of bleomycin was performed in 30 rats to induce PF, while Sham animals were subjected to instillation of saline solution. The treatment was performed using daily oral administration of distilled water, EOCW at 50, 100, and 200 mg/kg, and deflazacort (DFC). After 28 days, hemogram and bronchoalveolar lavage fluid (BALF), tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were assayed. Histological grading of PF, immunohistochemical expression of α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were also analyzed. The EOCW major compounds were found to be citronellal, geraniol, and citronellol. EOCW significantly reduced inflammation in BALF, reduced MDA levels, and increased SOD activity. EOCW attenuated histological grading of PF and reduced immunohistochemical expression of α-SMA and TGF-β in a dose-dependent way, likely due to the reduction of oxidative stress, inflammation, and TGF-β-induced myofibroblast differentiation.

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Geraniol activates Nrf-2/HO-1 signaling pathway mediating protection against oxidative stress-induced apoptosis in hepatic ischemia-reperfusion injury

Cited by 32 publications

References 64 publications

Geraniol Averts Methotrexate-Induced Acute Kidney Injury via Keap1/Nrf2/HO-1 and MAPK/NF-κB Pathways

Geraniol Averts Methotrexate-Induced Acute Kidney Injury via Keap1/Nrf2/HO-1 and MAPK/NF-κB Pathways

Preclinical and Clinical Antioxidant Effects of Natural Compounds against Oxidative Stress-Induced Epigenetic Instability in Tumor Cells

Cymbopogon winterianus Essential Oil Attenuates Bleomycin-Induced Pulmonary Fibrosis in a Murine Model

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