Evaluation of Nrf2/ARE Signaling Pathway in the Presence of Pentoxifylline as a Cryoprotectant in Mouse Spermatogonial Stem Cells

Sadeghiani, Ghazaleh; Khanehzad, Maryam; Gilani, Mohammad Ali Sadighi; Amidi, Fardin; Malekzadeh, Mehrnoush; Rastegar, Tayebeh

doi:10.1089/bio.2021.0167

Cited by 6 publications

(6 citation statements)

References 36 publications

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“…Although this work was not able to observe a significant decrease in phospho-Akt and phospho-ERK levels following pentoxifylline treatment, other studies reported that CHI3L1 inhibition led to decreased activity in these pathways [ 34 ] , and thus may have an impact on the Nfr2-Keap1 pathway. On the other hand, a recent publication reports that pentoxifylline can increase Nrf2 in non-cancer cells [ 63 ] . However, in the context of tumor cells, the effect of pentoxifylline on the Nfr2-Keap1 pathway is not yet known and therefore more studies are needed.…”

Section: Discussionmentioning

confidence: 99%

“…Another point to consider is that A549 and NCI-H460 cell lines have the Nfr2-Keap1 antioxidant response pathway activated [60] . Several studies demonstrated that overactivation of this pathway supports cancer progression and protects cancer cells from oxidative damage, leading to chemoresistance [61,62] . In fact, it is known that ERK and Akt signaling pathways upregulate Nrf2 and thus increase the Nrf2-Keap1 signaling [62] .…”

Section: Discussionmentioning

confidence: 99%

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Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Matos,

Peixoto da Silva,

Vasconcelos

et al. 2024

Cancer Drug Resist

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Aim: Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. Methods: The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between CHI3L1 gene expression and NSCLC patients’ survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Results: Pentoxifylline slightly decreased the expression levels of CHI3L1, β-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. Conclusion: This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Matos,

Peixoto da Silva,

Vasconcelos

et al. 2024

Cancer Drug Resist

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“…Nrf2, which neutralizes ROS by activating endogenous antioxidant enzymes, reduces inflammatory responses by blocking the transcriptional activity of NF-κB [33]. Under normal conditions, the Nrf2/Keap1 complex, deactivated in the cytoplasm, is separated by oxidative stress, which resists intracellular oxidative stress by inducing the nuclear translocation of Nrf2 [34]. This study confirmed that CH + CB or KACH + CB increase the expression of antioxidant enzymes, including HO-1, SOD, GPx, and GSTs by promoting the nuclear translocation of Nrf2 in LPS-stimulated RAW 264.7 macrophages more effectively than in a single treatment.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effect of Chestnut Honey and Cabbage Mixtures Alleviates Gastric Mucosal Damage

Kim,

Jin,

Lee

et al. 2024

Nutrients

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Gastritis, one of the most common gastrointestinal disorders, damages the stomach lining as it causes a disproportion between the protective and ruinous factors of the gastric system. Cabbage (CB) is widely used to treat gastric lesions but requires the addition of natural sweeteners to counteract its distinct bitter taste. Therefore, this study sought to determine whether the combination of chestnut honey (CH)—which is known for its dark brown color and high kynurenic acid (KA) content—or KA-increased CH (KACH) with CB (CH + CB or KACH + CB) exerts synergistic effects for improving both taste and efficacy. Before confirming the gastroprotective effects in indomethacin (INDO)-induced rats, the anti-inflammatory activities of CH + CB and KACH + CB were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. As a result, treatment with either CH + CB or KACH + CB downregulated pro-inflammatory cytokine levels in LPS-stimulated RAW 264.7 macrophages by regulating the translocation of nuclear factor kappa B. Furthermore, both CH + CB and KACH + CB not only enhanced the levels of antioxidant enzymes but also triggered the activation of nuclear factor erythroid-related factor 2. Based on these effects, CH + CB or KACH + CB effectively protected the gastric mucosa in INDO-induced rats. Therefore, this study suggests that CH + CB and KACH + CB exert stronger gastroprotective effects when used together.

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“…By considering the supporting role of Nrf2 to spermatogenesis and sperm quality, Sadeghiani et al [99] reported that pentoxifylline supplementation during freezing protocol and long-term storage protected mouse spermatogonial stem cell activating the antioxidant defense through the Nrf2/ARE signaling pathway. In addition, the transcription of NRF2, together with that referred to SOD1 and GPx1, was up-regulated in post-thawed buck semen after supplementation with antioxidants [100].…”

Section: Role Of Nrf2 In Long-term Storage Of Spermmentioning

confidence: 99%

Redox Homeostasis and Nrf2-Regulated Mechanisms Are Relevant to Male Infertility

Signorini,

Saso,

Ghareghomi

et al. 2024

Antioxidants

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Infertility represents a significant global health challenge, affecting more than 12% of couples worldwide, and most cases of infertility are caused by male factors. Several pathological pathways are implicated in male infertility. The main mechanisms involved are driven by the loss of reduction–oxidation (redox) homeostasis and the resulting oxidative damage as well as the chronic inflammatory process. Increased or severe oxidative stress leads to sperm plasma membrane and DNA oxidative damage, dysregulated RNA processing, and telomere destruction. The signaling pathways of these molecular events are also regulated by Nuclear factor-E2-related factor 2 (Nrf2). The causes of male infertility, the role of oxidative stress in male infertility and the Keap1-Nrf2 antioxidant pathway are reviewed. This review highlights the regulatory role of Nrf2 in the balance between oxidants and antioxidants as relevant mechanisms to male fertility. Nrf2 is involved in the regulation of spermatogenesis and sperm quality. Establishing a link between Nrf2 signaling pathways and the regulation of male fertility provides the basis for molecular modulation of inflammatory processes, reactive oxygen species generation, and the antioxidant molecular network, including the Nrf2-regulated antioxidant response, to improve male reproductive outcomes.

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Evaluation of Nrf2/ARE Signaling Pathway in the Presence of Pentoxifylline as a Cryoprotectant in Mouse Spermatogonial Stem Cells

Cited by 6 publications

References 36 publications

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Anti-Inflammatory Effect of Chestnut Honey and Cabbage Mixtures Alleviates Gastric Mucosal Damage

Redox Homeostasis and Nrf2-Regulated Mechanisms Are Relevant to Male Infertility

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