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histology of the stomach in control rats. a: non-glandular forestomach showing normal histological structure of stratified squamous keratinized (arrows) epithelium (e) with underlying submucosa (mu) and muscularis (m), B: fundus showing normal histological structure of gastric gland (G), and c: Pylorus showing normal histological structure of the mucosal layer (Mu) with crypts, h & e × 200.
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The current systemic treatments of the various solid tumors involve Cisplatin (CIS)-based chemotherapy. Due to its cytotoxicity, this approach is limited. Moreover, the safety of CIS is only discussed especially in breast and stomach cancers. Therefore, we, for the first time, explored the restorative efficacy of oleuropein (OLE), in stomach and lu...
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Background
Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family and is a key proto-oncogene in solid tumors. This pilot study investigated the safety and efficacy of pyrotinib in HER2-positive non-breast advanced solid tumors.
Patients and Methods
Twenty-five patients with HER2-positive advanced solid tumors excluding bre...
Citations
... A strong relationship between inflammation and tumor development has been recently identified and both are positively correlated with tumor metastasis, neovascularization, and tumor immunity [22]. Highdoses of OLP have a relevant impact on cisplatin-induced oxidative stress, genotoxicity and pathological changes in rat stomach and lung [23]. OLP downregulates tissue infiltration of macrophages and neutrophils by blocking OVA inhalation and ICAM-1, F4/80, CD68, and CD11b expression induced by cigarette smoke in mouse lungs [24]. ...
... Defining the mechanisms of action of drugs already used in clinical practice, and finding new pharmacological solutions is fundamental for the management of cancer [29,[40][41][42]. OLP exerts pharmacological benefits as antioxidant, anti-inflammatory, antiatherogenic, anticancer, antimicrobial, and antiviral activities [43,44], and high-doses of OLP reduce cisplatin-induced oxidative stress, genotoxicity and pathological changes in rat stomach and lung [23]. It is a food supplement [45] involved in the inhibition of cell proliferation and in the induction of apoptosis in cancer cell lines via different mechanisms. ...
IL-17A drives inflammation and oxidative stress, affecting the progression of chronic lung diseases (asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis). Oleuropein (OLP) is a polyphenolic compound present in olive oil and widely included in the Mediterranean diet. It exerts antioxidant and anti-inflammatory activities, oxidative stress resistance, and anticarcinogenic effects with a conceivable positive impact on human health. We hypothesized that OLP positively affects the mechanisms of oxidative stress, apoptosis, DNA damage, cell viability during proliferation, and cell growth in alveolar epithelial cells and tested its effect in a human alveolar epithelial cell line (A549) in the presence of IL-17A. Our results show that OLP decreases the levels of oxidative stress (Reactive Oxygen Species, Mitochondrial membrane potential) and DNA damage (H2AX phosphorylation-ser139, Olive Tail Moment data) and increases cell apoptosis in A549 cells exposed to IL-17A. Furthermore, OLP decreases the number of viable cells during proliferation, the migratory potential (Scratch test), and the single cell capacity to grow within colonies as a cancer phenotype in A549 cells exposed to IL-17A. In conclusion, we suggest that OLP might be useful to protect lung epithelial cells from oxidative stress, DNA damage, cell growth, and cell apoptosis. This effect might be exerted in lung diseases by the downregulation of IL-17A activities. Our results suggest a positive effect of the components of olive oil on human lung health.
... Thus, the development of myofibroblasts and the generation of extracellular matrix are diminished, and the advancement of pulmonary fibrosis is impeded.. [34][35][36][37][38][39] Our results are also consistent with other experimental studies reporting that the treatment with oleuropein on BLM induced fibrosis [40] and on cisplatin-induced oxidative stress reduce the MDA level in lung. [41] Dikmen et al. [42] reported that oleuropein raises CAT, SOD and GPX activities on Lipopolysaccharide LPS induced fibrosis. It was reported that hesperidin and oleuropein used separately alleviate BLM-IPF in a biphasic manner, through the modulation of the oxido-inflammatory markers of pulmonary fibrosis. ...
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia with acute lung damage leading to the deterioration of lung function and increased mortality risk. In this study, we aimed to investigate the effects of the orange coproduct extract (OCE) and the combination of pure hesperidin and oleuropein (HO) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM). Wistar rats were divided into 6 groups: the control group (G1), the BLM group (G2), 3 groups (G3, G4, G5) receiving a single dose of BLM combined with OCE extract at 100, 200 and 300 mg/kg and group 6 (G6) receiving a single dose of BLM combined with HO: both pure major phenolic compounds of OCE (hesperidin at 50 mg/kg) and olive leaves (oleuropein at 2.5 mg/kg). Oxidative stress in lung tissues was investigated using catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) assays and the measurement of malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. Treatment with OCE and HO were able to normalize the disturbance in oxidative markers' levels and showed a significant reduction in fibrosis score with no renal or hepatic toxic effects. In conclusion, OCE and HO exhibit antifibrotic effects on rat model of pulmonary fibrosis.
... Therefore, oxidant-antioxidant parameters (MDA, GSH, GSH-Px, catalase), inflammatory cytokines (TNF-α, IL-6 and IL-1β) and serum CK, CK-MB and cTnI levels were measured. Cisplatin causes damage to many tissues, such as the kidney, muscle atrophy, pancreas, brain, stomach and lung (Gong et al. 2021, Geyikoglu et al. 2017, Stošić et al. 2020, Oliveros et al. 2022). The numerous adverse effects of cisplatin-based therapy are often accompanied by increased oxidative damage and cell apoptosis in various tissues (Kumburovic et al. 2019). ...
This study investigated the cardioprotective effect of oleuropein against cisplatin-induced cardiac damage in terms of inflammatory, oxidative stress and cardiac parameters. In this study, 40 female Wistar albino rats were divided into four groups: control, cisplatin, oleuropein and cisplatin+oleuropein. To establish the experimental model, oleuropein (200 mg/kg) was administered for 14 days and cisplatin (7 mg/kg) was administered as a single dose on the seventh day. Cisplatin increased MDA cardiac parameters (CK, CK-MB and cTnI) and inflammatory cytokines (TNF-α, IL-1β and IL-6) in cardiac tissue and decreased GSH, GSH-Px and catalase levels. On the other hand, oleuropein improved cardiac parameters and decreased inflammatory cytokine and oxidative stress levels in cardiac tissue.
... The olive tree and its fruits have been considered symbols of peace and hope for centuries and are sacred in Holy Books. Olive and olive oil, the traditional and essential foods of the In addition, it has restorative efficacy in organ injuries induced by chemotherapy [6]. Gastric cancer is the most frequent and fatal malignancy in many parts of the world and it is generally related to harmful dietetic factors. ...
... Nowadays, the effectiveness and anticarcinogenic role of OLE and HT on gastric cancer cells has not been studied satisfactorily, and the underlying mechanisms of its action remain yet unknown. OLE has significantly reduced ROS levels, increased total antioxidant status levels, and repaired cisplatin-induced stomach cell damage in rats in an experimental investigation about the antioxidant and therapeutic effects of the substance [6]. Recently, the synthesis of Nano-Paramagnetic Oleuropein has been reported as an inducer of KRAS Over-Expression and inhibition of AGS Cancer Cells. ...
Background
Oleuropein (OLE), the main phenolic compound of the olive fruit and leaves, has many heathful effects. Gastric cancer is the most fatal malignancy in many parts of the world and it is generally related to harmful dietetic factors. The anticarcinogenic role of OLE in gastric cancer has not been studied sufficiently yet. In this study, we aimed to research the cytotoxic, genotoxic and apoptotic effects of OLE on gastric adenocancer (AGS) cells in vitro.
Methods and Results
A standard cell line derived from gastric adeno cancer (AGS) cells was employed, and its performance following a 24-hour exposure to OLE at various doses was examined. The ATP cell viability assay, 2’,7’-dichlorodihydrofluorescein-diacetate assay (H2DCF-DA) and alkaline single cell gel electrophoresis assay (Comet Assay) were used to study the cytotoxicity, production of reactive oxygen species (ROS) and genotoxicity respectively. The induction of apoptosis was discovered using flow cytometry. OLE reduced AGS cells viability about 60% at maximum concentration (500 µmol/L) and also resulted in approximately 100% DNA damage and about 40% apoptosis with necrosis in AGS cells depending on the increased doses. Cell viability was also significantly decreased in relation to increased intracellular reactive oxygen species (ROS) levels (p < 0.05 − 0.001).
Conclusions
Oleuropein has shown significant anticarcinogen effects against gastric adenocancer (AGS) cells in vitro. Oleuropein, a nutrient rich in olive and olive oil, seems to be both protective and therapeutic against gastric cancer and may be a new chemotherapeutic agent in the future.
... CIS-associated ALI can culminate in hypoxemia and mortality [5]. The multi-organ toxicity induced by CIS is associated with oxidative stress and inflammation [6][7][8][9]. Inflammation plays a key role in CIS-induced ALI, and a case report published by Ideguchi et al. demonstrated that eosinophilic pneumonia is an adverse effect of CIS [4]. In mice challenged with CIS, inflammatory cell infiltration, thickening of the interalveolar septa, ciliary fragmentation, and elevated levels of reactive oxygen species (ROS) were reported in the lung [10]. ...
... ALI is a serious side effect of CIS, with eosinophilic pneumonia, non-cardiogenic pulmonary edema, and alveolar-capillary membrane injury representing the characteristic clinical features [4,5]. Oxidative stress and inflammation-mediated tissue injury are implicated in CIS-induced cell death and lung injury [9,10,44]. Thus, attenuation of these pathological processes might be effective against CISinduced ALI. Given the immunomodulatory potential and the beneficial effect of AZM in preventing the inflammatory response [35], we evaluated its protective role against ALI, with emphasis on oxidative stress, inflammation, necroptosis, and the possible involvement of SIRT1 and PPARγ. ...
... Very recently, we demonstrated venous congestion, inflammatory exudates, thickened interalveolar septa and arterial wall, and perivascular edema in the lung of CIS-administered rats [44]. In support to these findings, infiltrating inflammatory cells, alveolar edema and damage, hemorrhage, and fibrotic changes were reported in other studies [8,9]. AZM effectively prevented CIS-induced lung tissue injury, with no evidence of edema or inflammatory cellular reaction in the alveoli, pinpointing its potent protective effect. ...
Acute lung injury (ALI) is one of the adverse effects of the antineoplastic agent cisplatin (CIS). Oxidative stress, inflammation, and necroptosis are linked to the emergence of lung injury in various disorders. This study evaluated the effect of the macrolide antibiotic azithromycin (AZM) on oxidative stress, inflammatory response, and necroptosis in the lungs of CIS-administered rats, pinpointing the involvement of PPARγ, SIRT1, and Nrf2/HO-1 signaling. The rats received AZM for 10 days and a single dose of CIS on the 7th day. CIS provoked bronchial and alveolar injury along with increased levels of ROS, MDA, NO, MPO, NF-κB p65, TNF-α, and IL-1β, and decreased levels of GSH, SOD, GST, and IL-10, denoting oxidative and inflammatory responses. The necrop-tosis-related proteins RIP1, RIP3, MLKL, and caspase-8 were upregulated in CIS-treated rats. AZM effectively prevented lung tissue injury, ameliorated oxidative stress and NF-κB p65 and pro-in-flammatory markers levels, boosted antioxidants and IL-10, and downregulated necroptosis-related proteins in CIS-administered rats. AZM decreased the concentration of Ang II and increased those of Ang (1-7), cytoglobin, PPARγ, SIRT1, Nrf2, and HO-1 in the lungs of CIS-treated rats. In conclusion , AZM attenuated the lung injury provoked by CIS in rats through the suppression of inflammation , oxidative stress, and necroptosis. The protective effect of AZM was associated with the up-regulation of Nrf2/HO-1 signaling, cytoglobin, PPARγ, and SIRT1.
... CIS caused lung injury manifested by the histopathological changes in the bronchi and lungs, including inflammatory changes, inflammatory exudates, thickening of the interalveolar septa, venous congestion, deformed and thickened arterial wall, and perivascular edema. CIS-induced histopathological alterations, such as alveolar septal fibrosis, leukocyte infiltration, hemorrhage, alveolar edema, and severe alveolar damage have been previously observed, pinpointing its pulmonary toxicity [8,9]. These changes were ...
... CIS caused lung injury manifested by the histopathological changes in the bronchi and lungs, including inflammatory changes, inflammatory exudates, thickening of the interalveolar septa, venous congestion, deformed and thickened arterial wall, and perivascular edema. CIS-induced histopathological alterations, such as alveolar septal fibrosis, leukocyte infiltration, hemorrhage, alveolar edema, and severe alveolar damage have been previously observed, pinpointing its pulmonary toxicity [8,9]. These changes were potently ameliorated by the administration of CAN, establishing its protective effect against CIS pulmonary intoxication. ...
... Owing to the role ROS and inflammation play in CIS-induced lung injury [8][9][10][11], we assumed that amelioration of oxidative stress and inflammation mediated, at least in part, the protective effect of CAN. In support of previous studies [8,9], CIS caused oxidative stress evidenced by elevated TBARS, NO, and LPO along with decreased GSH and SOD. ...
Cisplatin (CIS) is an effective chemotherapeutic agent against different cancers. The use of CIS is associated with acute lung injury (ALI) and other adverse effects, and oxidative stress and inflammation were implicated in its toxic effects. Candesartan (CAN), an angiotensin II (Ang II) receptor blocker, showed beneficial effects against oxidative stress and inflammation. Therefore, this study investigated the potential of CAN to prevent CIS-induced oxidative stress, inflammation, and lung injury in rats, pointing to the involvement of TLR4/NF-κB, JAK1/STAT3, PPARγ, and Nrf2/HO-1 signaling. The rats received CAN (5 mg/kg) for 10 days and were challenged with a single dose of CIS (7 mg/kg) on day 7. CIS caused injury to the alveoli and the bronchial tree, increased lipid peroxidation, nitric oxide, myeloperoxidase, TLR-4, NF-κB p65, iNOS, TNF-α, IL-6, IL-1β, and caspase-3, and decreased cellular antioxidants and IL-6 in the lungs of rats. CAN effectively prevented tissue injury, suppressed TLR-4/ NF-κB signaling, and ameliorated oxidative stress, inflammatory markers, and caspase-3 in CIS-administered rats. CAN enhanced antioxidants and IL-10, decreased Ang II, increased Ang (1–7), suppressed the phosphorylation of JAK1 and STAT3, and upregulated SOCS3 in CIS-administered rats. These effects were associated with the downregulation of Keap1 and enhanced Nrf2, GCLC, HO-1, and PPARγ. In conclusion, CAN prevented CIS-induced lung injury by attenuating oxidative stress, suppressing TLR-4/NF-κB and JAK1/STAT3 signaling, Ang II, and pro-inflammatory mediators, and upregulating PPARγ, and Nrf2/HO-1 signaling.
... Several in vitro studies have highlighted the antitumor role of quercetin: for example, in ovarian carcinoma (SKOV3 cell line), quercetin induced a decrease in cyclin D1, with consequent arrest in the S and G2/M phases of the cellular cycle. In human leukemia (U937 cell line), quercetin has been shown to induce cell cycle arrest at G2/M following the decrease in cyclins D, E, and E2F, and in osteosarcoma cells (HOS), quercetin was able to induce changes in the G0/G1 phase [140][141][142]. In addition, quercetin modulates the regulation of p53related pathways, inhibiting the activity of CDK2 and cyclins A and B. Direct involvement of p53 was also demonstrated in breast cancer, where the MDA-MB-453 cell line increased the expression of this protein [143,144]. ...
Cancer is one of the leading causes of death globally, associated with multifactorial pathophysiological components. In particular, genetic mutations, infection or inflammation, unhealthy eating habits, exposition to radiation, work stress, and/or intake of toxins have been found to contribute to the development and progression of cancer disease states. Early detection of cancer and proper treatment have been found to enhance the chances of survival and healing, but the side effects of anticancer drugs still produce detrimental responses that counteract the benefits of treatment in terms of hospitalization and survival. Recently, several natural bioactive compounds were found to possess anticancer properties, capable of killing transformed or cancerous cells without being toxic to their normal counterparts. This effect occurs when natural products are associated with conventional treatments, thereby suggesting that nutraceutical supplementation may contribute to successful anticancer therapy. This review aims to discuss the current literature on four natural bioactive extracts mostly characterized by a specific polyphenolic profile. In particular, several activities have been reported to contribute to nutraceutical support in anticancer treatment: (1) inhibition of cell proliferation, (2) antioxidant activity, and (3) anti-inflammatory activity. On the other hand, owing to their attenuation of the toxic effect of current anticancer therapies, natural antioxidants may contribute to improving the compliance of patients undergoing anticancer treatment. Thus, nutraceutical supplementation, along with current anticancer drug treatment, may be considered for better responses and compliance in patients with cancer. It should be noted, however, that when data from studies with bioactive plant preparations are discussed, it is appropriate to ensure that experiments have been conducted in accordance with accepted pharmacological research practices so as not to disclose information that is only partially correct.
... Interstitial inflammation, fibrosis, structural pulmonary damage, and other severe complications have also been reported during cisplatin chemotherapy [5]. These adverse effects of cisplatin-induced pulmonary damage may be due to the ability of cisplatin to produce oxidant-induced inflammatory and fibrotic lesions in lungs [6]. Previous study reported that cisplatin induces ROS formation and generates oxygen free radicals and initiates lipid peroxidation and reduces enzymatic and nonenzymatic antioxidant levels [7]. ...
Silver nanoparticles (AgNPs) are gaining interest in medical applications for their prominent antibacterial and antimicrobial potentials. AgNPs possess remarkable anti-inflammatory and antioxidant activities and enhances wound healing. The main objective of the current study was to investigate the therapeutic effect of administration of AgNPs on cisplatin (CP) induced pulmonary inflammation in rats. Sixty male albino rats were used in this study. Rats were divided into 6 groups (n=10). Group I control group. Group II and III control groups received AgNPs at doses (5 and 10 ppm). Group IV CP group received CP (2.5 mg/kg). Group V and VI CP group received AgNPs (5, and 10 ppm). All doses were administered intraperitoneally once a day for 4 weeks. Oxidative stress and antioxidant status, inflammatory mediators, fibrogenic as well as apoptotic markers were determined in lung tissues. The results revealed that rats treated with CP showed remarkable elevation in lung tissues MDA, TNF-α, IFN-γ, IL-6, CRP, Fibrinogen and P53 levels associated with depression in SOD, GSH and CAT activities. However, administration of AgNPs (5 or 10 ppm) to CP group resulted in significant amelioration of the aforementioned parameters in a dose dependent manner. Histopathological investigation of lung tissues of CP group demonstrated disruption of normal lung architecture and lung injury. However, treatment with AgNPs revealed significant improvement in lung tissue against CP- induced inflammatory changes and lung tissue damage. It could be concluded that AgNPs exert potent cytoprotective effects via combating oxidative stress, inflammation, fibrogenic and apoptotic markers and repairing histopathological changes in lung tissues.
... Herbal ingredients with anti-inflammatory effects are known to be effective in the inhibition of the NF-κB cascade and the cytokines released by it. Various studies have reported that oleuropein, which is a compound present in olive that is one of the main components of the Mediterranean diet, has a protective effect in multiple organ injury models [20,64,65]. In the present study, NF-κB, TNF-α, and IL-6 levels were found to be significantly decreased in the group treated with oleuropein. ...
Acute lung injury (ALI) is one of the most common causes of death in diseases with septic shock. Oleuropein, one of the important components of olive leaf, has antioxidant and anti-inflammatory effects. The objective of this study was to investigate the effects of oleuropein on lipopolysaccharide (LPS)-induced ALI in rats. Oleuropein was administered to rats at a dose of 200 mg/kg for 20 days and LPS was given through intratracheal administration to induce ALI. The study was terminated after 12 h. The results showed that in the group treated with oleuropein, inflammatory cytokines and oxidative stress decreased in serum, bronchoalveolar lavage fluid (BALF), and lung tissue, and there were significant improvements in the picture of acute interstitial pneumonia (AIP) caused by LPS in histopathological examination. Based on the findings of the present study, oleuropein showed protective effects against LPS-induced ALI.
... In cisplatin-induced oxidative stress it increased plasma antioxidant capacity (trolox-equivalent antioxidant capacity), significantly reduced total oxidant state and reduced 9-OH-dG, a marker of oxidative DNA damage (Geyikoglu et al., 2017). The same results were observed in rat kidneys (Geyikoglu et al., 2017b), in stomach and lungs (Geyikoglu et al., 2017c), and, most relevant to this article, in pancreas (Bakir, Geyikoglu, Koc, & Cerig, 2018). In bisphenol A-treated rats, oleuropein significantly reduced malondialdehyde levels and increased COD and TEAC in both livers and kidneys of rats (A. ...
