Fig 1 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Cell viability assessment by MTS assay. A Effect of different concentrations of CYL against percentage of cell viability of WI-38 and A549 cells after 24 h incubation for evaluating IC 50 . B Cell viability-response curve of SES in WI-38 cells after incubation for 24
Source publication
Cyclophosphamide (CYL) is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia. Though, CYL has been documented to induce lung toxicity. Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns (DAMPs). Sesamol (SES) is a natural antioxidant...
Contexts in source publication
Context 1
... cytotoxic effect of CYL was evaluated by determining the effect of different concentrations of CYL (100-1.56 µM) on the viability of WI-38 and A549 cells after 24 h of incubation using MTS assay. As presented in Fig. 1A, the cell viability was decreased by increasing the concentration of CYL when compared with untreated cells (control group) and the half-maximal inhibitory concentrations (IC 50 ) were calculated to be 40.7 µM and 10.5 µM respectively for both cell lines. On the other hand, to select the suitable dose for SES, cell viability was also ...
Context 2
... SES, cell viability was also evaluated by MTS assay after treating WI-38 and A549 cells with different concentrations of SES (200-6.25 µM) and incubated for 24 and 48 h. According to SES concentration-cell viability response curve, the IC 50 was estimated after 24 h and 48 h of incubation to be 110.4 µM and 48.9 µM respectively for WI-38 cells (Fig. 1B) and 69 µM and 21 µM respectively for A549 cells (Fig. 1C). Accordingly, the concentration of 12.5 µM of SES was selected to study its protective effect against CYL-induced lung toxicity, based on using the highest dose with maximal cell viability when compared to the control group. By trypan exclusion assay, pretreatment of WI-38 cells ...
Context 3
... treating WI-38 and A549 cells with different concentrations of SES (200-6.25 µM) and incubated for 24 and 48 h. According to SES concentration-cell viability response curve, the IC 50 was estimated after 24 h and 48 h of incubation to be 110.4 µM and 48.9 µM respectively for WI-38 cells (Fig. 1B) and 69 µM and 21 µM respectively for A549 cells (Fig. 1C). Accordingly, the concentration of 12.5 µM of SES was selected to study its protective effect against CYL-induced lung toxicity, based on using the highest dose with maximal cell viability when compared to the control group. By trypan exclusion assay, pretreatment of WI-38 cells with SES 12.5 µM 24 h before CYL, significantly ...
Similar publications
Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon and a serious environmental pollutant. BaP is formed by the incomplete combustion of organic matter at high temperatures. In addition, tobacco smoke and many foods, especially charbroiled food and grilled meats, contain BaP and can cause it to enter human body. Melatonin, a pineal gland horm...
Citations
... Cyclophosphamide (CYL) is a DNA alkylating agent commonly used in cancer treatment. Active CYL metabolites can suppress cancer cells (Ahlmann and Hempel 2016;El-Emam 2021;Natsuko et al. 2010). The effect of CYL on T cells is complex and dose dependent, and T cell lymphopenia and immunomodulatory effects can develop into immunosuppressive effects at higher doses (Huyan et al. 2011;Gladstone et al. 2002). ...
Background and aim
Morinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo.
Methods
In vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells.
Results
Individual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group.
Conclusions
The present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.
... To explore the relevant molecular mechanisms, we further detected the mRNA levels of the cellular autophagy-related gene Beclin-1, apoptosis-related gene Caspase-3, and inflammation-key gene NF-κB [23][24][25][26]. The results showed that the mRNA levels of Beclin-1 were significantly higher in A549 cells with FPS-ZM1treatment than those with non-treatment at48 h and 72 h post H1N1 infection (Fig. 2D-F), while the mRNA levels of Caspase-3 and NF-κB were significantly lower in A549 cells with FPS-ZM1 treatment than those with non-treatment ( Fig. 2G-L). ...
... Autophagy is an important intracellular process that plays a crucial role in the maintenance of cellular homeostasis and the regulation of cellular differentiation and survival [49]. The affection of the mediators of autophagy was regarded as a possible explanation for the toxic effects of CPA on the lungs [5]. As evidenced in the current study, the autophagic stream was proven to be significantly inhibited in the lung tissues following the administration of CPA. ...
Background and objectives: Cyclophosphamide (CPA) is an alkylating agent that is used for the management of various types of malignancies and as an immunosuppressive agent for the treatment of immunological disorders. However, its use is limited by its potential to cause a wide range of pulmonary toxicities. Amentoflavone (AMV) is a flavonoid that had proven efficacy in the treatment of disease states in which oxidative stress, inflammation, and apoptosis may play a pathophysiologic role. This study investigated the potential ameliorative effects of the different doses of AMV on CPA-induced pulmonary toxicity, with special emphasis on its antioxidant, anti-inflammatory, and apoptosis-modulating effects. Materials and methods: In a rat model of CPA-induced pulmonary toxicity, the effect of AMV at two dose levels (50 mg/kg/day and 100 mg/kg/day) was investigated. The total and differential leucocytic counts, lactate dehydrogenase activity, and levels of pro-inflammatory cytokines in the bronchoalveolar lavage fluid were estimated. Also, the levels of oxidative stress parameters, sirtuin-1, Keap1, Nrf2, JAK2, STAT3, hydroxyproline, matrix metalloproteinases 3 and 9, autophagy markers, and the cleaved caspase 3 were assessed in the pulmonary tissues. In addition, the histopathological and electron microscopic changes in the pulmonary tissues were evaluated. Results: AMV dose-dependently ameliorated the pulmonary toxicities induced by CPA via modulation of the SIRT-1/Nrf2/Keap1 axis, mitigation of the inflammatory and fibrotic events, impaction of JAK-2/STAT-3 axis, and modulation of the autophagic and apoptotic signals. Conclusions: AMV may open new horizons towards the mitigation of the pulmonary toxicities induced by CPA.
... Evidence suggests that inhibiting RAGE exerts a therapeutic effect in ARDS animals by restoring alveolar epithelial permeability and pulmonary fluid clearance [19]. Interestingly, it was reported that RAGE mediates autophagy which participates in the pathogenesis of different lung diseases, including ALI [20]. A recent study found that the suppression of autophagy improved pulmonary epithelial cell viability and tight junctions [21]. ...
Background
Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death.
Methods
Acute lung injury animal models were established using C57BL/6 and Ager gene knockout ( Ager −/− mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test.
Results
The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager −/− mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway.
Conclusion
RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells.
... The active anticancer agent acting on DNA causing cancer cell mortality is phosphoramide, whereas acrolein is the CP-toxic metabolite leading to toxicity (Sun et al. 2014a, b). CP is associated with genotoxicity and numerous hazardous impacts on numerous organs due to its capability to stimulate oxidative burden with consequent cell death (El-Emam 2020). Among these toxicities are cardiotoxicity (Iqubal et al. 2019), hepatotoxicity (Abdelfattah-Hassan et al. 2019), nephrotoxicity (Sharma et al. 2017), in addition to lung toxicity (El-kashef 2018;Abdel-Latif et al. 2020). ...
Cyclophosphamide (CP)-induced lung toxicity is a remaining obstacle against the beneficial use of this chemotherapeutic agent. More considerations were given to the role of Alogliptin (ALO) in ameliorating CP-induced toxicities in many tissues. We designed this study to clarify the protective potential of ALO against CP-induced lung toxicity in rats. ALO was administered for 7 days. Single-dose CP was injected on the 2nd day (200 mg/kg: i.p.) to induce lung toxicity. Rats were divided into four groups: control, ALO-treated, CP-treated and ALO + CP-treated group. Leucocytic count, total proteins, LDH activity, TNF-α, and IL-6 were estimated in the bronchoalveolar lavage fluid (BALF). The oxidative/antioxidants (MDA, Nrf2, TAO and GSH), inflammatory (NFκB), fibrotic (TGF-β1) and apoptotic (PI3K/Akt/FoxO1) markers in pulmonary homogenates were biochemically evaluated. Rat lung sections were examined histologically (light and electron microscopic examination) and immunohistochemically (for iNOS and CD68 positive alveolar macrophages). CP significantly increased oxidative stress, inflammation, fibrosis, and apoptosis markers as well as deteriorated the histopathological pulmonary architecture. These hazardous effects were significantly ameliorated by ALO treatment. ALO protected against CP-induced lung toxicity by mitigating the oxidative, inflammatory and fibrotic impacts making it a promising pharmacological therapy for mitigating CP-induced lung toxicity.
Graphical abstract
We fabricated silver nanoparticles (AgNPs) using Pterorhachis zenkeri , characterized by Atomic Force Microscopy (AFM) and determined their antioxidant potentials in vitro . Results confirmed the fabrication of AgNPs by using P. zenkeri as a bioreducing agent for the first time. AgNPs possessed potent antioxidant activity in vitro. Furthermore, the TM3 cells were treated for 24 h with AgNPs, vitamin E and cyclophosphamide (CP) at different concentrations (25, 50, 100, 250 and 500 µg/ml). The cells morphology, apoptosis, mitochondrial membrane depolarisation (MMD), Reactive Oxygen Species (ROS), caspase 3/9, oxidative stress-related enzymes, testosterone, and the mRNAexpression of steroidogenic acute regulatory protein (StAR) were measured. Results revealed that AgNPs, vitamin E and CP decreased the cell viability in a dose-dependent manner, but did not affect the TM3 cells morphology after treatment. The cytotoxicity of CP in TM3 cells was alleviated after AgNPs application. For instance, AgNPs significantly (p<0.001-0.05) reduced the MMD, ROS production, and caspase 3/9 activities, but increased the activities of superoxide dismutase, catalase and glutathione peroxidase in the TM3 cells. Moreover, AgNPs improved testosterone production by activating StAR machineries. These results indicate that AgNPs/ P. zenkeri could be a potential alternative drug in the management of oxidative stress and androgen deficit associated with CP chemotherapy.
Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.
The alkylation of sesamol with camphene in the presence of acid heterogeneous catalysts (KSF, Fiban K-1, Amberlyst 15) was studied. The O-alkylation was found to be the main direction of the reaction under the conditions studied. For alkyl sesamol derivatives, the erythrotoxicity, membrane-protective and antioxidant activities were evaluated in in vitro models. It was established that 6-isobornylbenzo[d][1,3]dioxol-5-ol is distinguished by a high antioxidant activity in biologically relevant test systems and is significantly superior to sesamol in both the ability to inhibit the Fe2+/ascorbate-induced brain lipid oxidation and the protection of erythrocytes under the conditions of oxidative hemolysis.
