Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy

doi:10.1016/j.taap.2016.10.002

Cited by 16 publications

(7 citation statements)

References 69 publications

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“…OME also has antioxidant activities (in vitro), by blocking hydroxyl radical ( ⋅ OH), preventing apoptosis and necrosis [73], inducing nicotinamide adenine dinucleic acid (NADPH) kinase oxidoreductase production [74], and increasing endogenous antioxidants [72]. In vivo and in vitro studies report inhibition of necrosis by activation of TNF-α, interleukin B [75], and proinflammatory cytokines [76].…”

Section: Antioxidant and Anti-inflammatory Effects Several In Vivo Smentioning

confidence: 99%

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Paz

Alencar

Lima

et al. 2020

Oxidative Medicine and Cellular Longevity

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Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.

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Section: Antioxidant and Anti-inflammatory Effects Several In Vivo Smentioning

confidence: 99%

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Paz

Alencar

Lima

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Recent studies have shown that Nrf2 can protect liver against ischemia reperfusion injury [ 46 ]. Both HO-1 and NQO1 are key response genes, and their activation can protect against oxidative damage in cells [ 47 ]. HO-1 exerts cytoprotection by inhibiting inflammation and apoptosis [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen protects against liver injury during CO2 pneumoperitoneum in rats

Chen

Jiang

et al. 2017

Oncotarget

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The aim of the current study was to identify the protective effect of hydrogen gas against liver injury during CO2 pneumoperitoneum. Rats were randomly divided into three groups: control group (C group), pneumoperitoneum group (P15 group) and hydrogen group (H2 group). Rats in the C group were subjected to anesthesia for 90 min. Rats in the P15 group received an abdominal insufflation of CO2 for 90 min at an intra-abdominal pressure of 15 mmHg. Rats in the H2 group received a hypodermic injection of hydrogen gas (0.2 mL/kg) and after 10 min they received an abdominal insufflation of CO2 for 90 min at an intra-abdominal pressure of 15 mmHg. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to evaluate liver function. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) content were measured to evaluate oxidative stress. Nuclear factor E2-related factor 2 (Nrf2) and Nrf2 downstream target genes, apoptosis-related genes and inflammatory cytokine mRNA and protein expression were detected. Liver injury was detected under the microscope. Our results revealed that liver function, antioxidants content, inflammation and liver injury were improved after hydrogen preconditioning in H2 group compared with P15 group. Overall, our results revealed that subcutaneous hydrogen injection could exert a protective effect against liver injury during CO2 pneumoperitoneum through reducing oxidative stress, cell apoptosis and inflammatory cytokines release.

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“…Each cycle included denaturation at 95 °C for 1 min, annealing at appropriate temperature for 1 min, extension at 72 °C for 1 min, followed by a final extension at 72 °C for 10 min. The PCR primers used for PSMB5, [(sense) 5′-GAG-ATC-AAC-CCA-TAC-CTG-CTA-G-3′ and (antisense) 5′-AGT-CAC-CCC-AAG-AAA-CAC-AAG-C-3′] [42], Nrf2, [(sense) 5′-AAA-CCA-GTG-GAT-CTG-CCA-AC-3′ and (antisense) 5’-GAC-CGG-GAA-TAT-CAG-GAA-CA-3′] [43], and GAPDH, [(sense) 5’-TCA-AGA-TCA-TCA-GCA-ATG-CCT-CC-3′ and (antisense) 5′-AGT-GAG-CTT-CCC-GTT-CAG-C-3′], were synthesized by MWG-Biotech AG (Ebersberg, Germany). The annealing temperature was 58 °C, 49 °C and 60 °C for PSMB5, Nrf2 and GAPDH, respectively.…”

Section: Methodsmentioning

confidence: 99%

UVB-mediated down-regulation of proteasome in cultured human primary pterygium fibroblasts

et al. 2018

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BackgroundPterygium is a condition characterized by epithelial overgrowth of the cornea, inflammatory cell infiltration and an abnormal extracellular matrix accumulation. Chronic UV exposure is considered as a pathogenic factor of this disease. Proteasome is an intracellular multi-subunit protease complex that degrades intracellular proteins. Among proteasome subunits the β5 (PSMB5), bearing chymotrypsin-like activity. It is considered as the main proteasome subunit and its expression is mediated by Nrf2-ARE pathway in many cell types. This study investigates the expression of PSMB5 in pterygium and the effect of UVB irradiation on its expression and activity in pterygium fibroblasts.MethodsNormal conjunctival and pterygium specimens were obtained from the bulbar conjunctiva of patients undergoing cataract surgery and from patients with pterygium undergoing surgical removal of primary tissue, respectively. Fibroblasts were isolated upon treatment of specimens with clostridium collagenase. The expression of PSMB5 and Nrf2 in tissues and cells was ascertained by RT-PCR analysis and western blotting. Cell survival was measured by the MTT method and the proteasome chymotrypsin-like activity was determined by fluorometry.ResultsRT-PCR analysis showed that the expression of PSMB5 was significantly lower in pterygium than in normal conjunctiva. The expression of PSMB5 was mediated by the Nrf2/ARE pathway as indicated by using the Nrf2 activator Oltipraz. The expression of PSMB5 and Nrf2 by pterygium fibroblasts was suppressed in a dose dependent manner following UVB radiation of 0–50 mJ/cm2 doses. The expression of PSMB5, but not of Nrf2, remained at almost the control levels, when UVB exposure was performed after pre-incubation of cells with the src kinases inhibitor PP2. UVB irradiation had very low deleterious effect on fibroblasts survival, while it did not affect the proteasome chymotrypsin-like activity.ConclusionIn pterygium fibroblasts, UVB exposure leads to down-regulation of Nrf2/ARE-mediated PSMB5 gene expression, in which src kinases may be implicated. This effect may be partially responsible for the lower expression of PSMB5 detected in pterygium as compared to normal conjunctiva.

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Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

Cited by 16 publications

References 69 publications

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Hydrogen protects against liver injury during CO2 pneumoperitoneum in rats

UVB-mediated down-regulation of proteasome in cultured human primary pterygium fibroblasts

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