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Background: Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.
Methods: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as...
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Context 1
... analyze the clinical factors which could influence gastric mucosal injury in aspirin users, we compared the clinical characteristics of subgroup A and subgroup B, including age, gender, and medical history [ Table 2]. Results indicated that the proportion of male gender (P = 0.021), previous cerebrovascular disease (P = 0.028), previous peptic ulcer (P < 0.010), and dual anti-platelet medication (the combination of aspirin and clopidogrel) (P = 0.016) in mucosal injury group were higher than that in the noninjury group. ...
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Objective To evaluate the efficacy and safety of rabeprazole coadministration with low-dose aspirin (LDA).
Methods From 2015 to 2018, we conducted a large-scale, multicenter, prospective observational study to assess the safety and efficacy of treatment with rabeprazole (5 or 10 mg/day) in combination with LDA.
Results The incidence of adverse reac...
Background:
Patients taking low-dose aspirin have a higher incidence of gastroduodenal ulcers and higher risk of upper gastrointestinal bleeding than patients who do not. Thienopyridine antiplatelet agents may similarly cause bleeding gastroduodenal erosions and ulcers. The incidence of gastrointestinal bleeding is reported to be higher when these...
AIM
To assess the prevalence of possible risk factors of upper gastrointestinal bleeding (UGIB) and their age-group specific trend among the general population and osteoarthritis patients.
METHODS
We utilized data from the National Health Insurance Service that included claims data and results of the national health check-up program. Comorbid cond...
Non-steroidal anti-inflammatory drug (NSAID) use increases the risk of gastrointestinal complications such as ulcers or bleeding. The presence of factors like advanced age, history of peptic ulcer, Helicobacter pylori infection and the use of anticoagulants or antiplatelet agents increase this risk further. COX-2 inhibitors and antisecretory drugs,...
Background:
Non-variceal upper gastrointestinal bleeding (NVUGIB) secondary to peptic ulcer disease is a medical digestive emergency and could be one of the most serious adverse drug reactions.
Objective:
To identify the frequency of diagnosis of NVUGIB secondary to peptic ulcer disease.
Methods:
Prospective and epidemiological study conducted...
Citations
... Notably, the alleles of the PTGS1 and ADRA2A genes, associated with AR and/or high AA-induced aggregation in our study, correlated with a reduced risk of complications from the gastrointestinal tract when taking aspirin in other studies [61][62][63]. This may indicate a role in stimulating platelet activity in carriers of these alleles. ...
Aspirin resistance (AR) is a pressing problem in current ischemic stroke care. Although the role of genetic variations is widely considered, the data still remain controversial. Our aim was to investigate the contribution of genetic features to laboratory AR measured through platelet aggregation with arachidonic acid (AA) and adenosine diphosphate (ADP) in ischemic stroke patients. A total of 461 patients were enrolled. Platelet aggregation was measured via light transmission aggregometry. Eighteen single-nucleotide polymorphisms (SNPs) in ITGB3, GPIBA, TBXA2R, ITGA2, PLA2G7, HMOX1, PTGS1, PTGS2, ADRA2A, ABCB1 and PEAR1 genes and the intergenic 9p21.3 region were determined using low-density biochips. We found an association of rs1330344 in the PTGS1 gene with AR and AA-induced platelet aggregation. Rs4311994 in ADRA2A gene also affected AA-induced aggregation, and rs4523 in the TBXA2R gene and rs12041331 in the PEAR1 gene influenced ADP-induced aggregation. Furthermore, the effect of rs1062535 in the ITGA2 gene on NIHSS dynamics during 10 days of treatment was found. The best machine learning (ML) model for AR based on clinical and genetic factors was characterized by AUC = 0.665 and F1-score = 0.628. In conclusion, the association study showed that PTGS1, ADRA2A, TBXA2R and PEAR1 polymorphisms may affect laboratory AR. However, the ML model demonstrated the predominant influence of clinical features.
... Through a recent systematic review (2020) (Forgerini et al., 2021a), three studies that evaluated single-nucleotide polymorphisms (SNPs) in the PTGS1 and NOS3 genes and the UGIB risk were identified (van Oijen et al., 2006;Wu et al., 2016;Mallah et al., 2020). ...
... In 2016, Wu et al. evaluated this same SNP and two others (rs1330344 and rs3842788), and association data were only reported for the rs1330344 variant, which identified an increased risk of UGIB in homozygous patients (OR: 2.17, CI 95%: 1.01-4.66) (Wu et al., 2016). Finally, Mallah et al. (2020) evaluated three SNPs in the PTGS1 gene (rs1330344, rs384287, and rs5788) and one SNP in the NOS3 gene (rs1799983). ...
... Except for rs1036114, which is an unprecedented analysis, three other studies assessed the influence of rs3842787, rs1330344, and rs5788 on the UGIB risk (van Oijen et al., 2006;Wu et al., 2016;Mallah et al., 2020). In line with our findings, Mallah and colleagues suggested that rs1330344 was associated with an increased risk of UGIB in LDA users (Mallah et al., 2020), and Wu and colleagues reported rs1330344 as a possible risk factor for the gastric mucosal injury induced by LDA (Wu et al., 2016),whereas two studies did not identify association between genetic variants rs3842787 and rs5788 and UGIB risk (van Oijen et al., 2006;Wu et al., 2016). ...
... Marked interindividual differences with respect to their response to NSAIDs have long been recognized and attributed to many factors including genetic variations in metabolizing enzymes [17][18][19][20]. Several studies also reported a possible relationship between genetic variations in users of NSAIDs and gastrointestinal disorders [21][22][23][24][25][26][27]. In this context, genetic pharmacokinetic factors are of special importance since variations in genes involved in drug metabolism might alter their expression and thus increase the risk of undesirable effects like bleeding and cardiovascular events. ...
Background
Interindividual genetic variations contribute to differences in patients’ response to drugs as well as to the development of certain disorders. Patients who use non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal disorders, mainly upper gastrointestinal haemorrhage (UGIH). Studies about the interaction between NSAIDs and genetic variations on the risk of UGIH are scarce. Therefore, we investigated the effect of 16 single nucleotide polymorphisms (SNPs) involved in drug metabolism on the risk of NSAIDs-induced UGIH.
Materials and methods
We conducted a multicenter case-control study of 326 cases and 748 controls. Participants were sub-grouped into four categories according to NSAID exposure and genetic profile. We estimated odds ratios (ORs) and their 95% confidence intervals (CI) using generalized linear mixed models for dependent binomial variables and then calculated the measures of interaction, synergism index (S), and relative excess risk due to interaction (RERI). We undertook stratified analyses by the type of NSAID (aspirin, non-aspirin).
Results
We observed an excess risk of UGIH due to an interaction between any NSAID, non-aspirin NSAIDs or aspirin and carrying certain SNPs. The greatest excess risk was observed for carriers of: rs2180314:C>G [any NSAID: S = 3.30 (95%CI: 1.24–8.80), RERI = 4.39 (95%CI: 0.70–8.07); non-aspirin NSAIDs: S = 3.42 (95%CI: 1.12–10.47), RERI = 3.97 (95%CI: 0.44–7.50)], and rs4809957:A>G [any NSAID: S = 2.11 (95%CI: 0.90–4.97), RERI = 3.46 (95%CI: −0.40–7.31)]. Aspirin use by carriers of rs6664:C>T is also associated with increased risk of UGIH [ORaspirin(+),wild-type: 2.22 (95%CI: 0.69–7.17) vs. ORaspirin(+),genetic-variation: 7.72 (95%CI: 2.75–21.68)], yet larger sample size is needed to confirm this observation.
Conclusions
The joint effect of the SNPs s2180314:C>G and rs4809957:A>G and NSAIDs are more than three times higher than the sum of their individual effects. Personalized prescriptions based on genotyping would permit a better weighing of risks and benefits from NSAID consumption.
KEY MESSAGES
Multicenter case-control study of the effect of genetic variations involved in drug metabolism on upper gastrointestinal haemorrhage (UGIH) induced by NSAIDs (aspirin and non-aspirin).
There is a statistically significant additive synergism interaction between certain genetic polymorphisms and NSAIDs on UGIH: rs2180314:C>G and rs4809957:A>G. The joint effect of each of these single nucleotide polymorphisms and NSAIDs on UGIH is more than three times higher than the sum of their individual effects.
Genetic profiling and personalized prescriptions would be useful in managing the risks and benefits associated with NSAIDs.
... Through a recent systematic review (2020) (Forgerini et al., 2021a), three studies that evaluated single-nucleotide polymorphisms (SNPs) in the PTGS1 and NOS3 genes and the UGIB risk were identified (van Oijen et al., 2006;Wu et al., 2016;Mallah et al., 2020). ...
... In 2016, Wu et al. evaluated this same SNP and two others (rs1330344 and rs3842788), and association data were only reported for the rs1330344 variant, which identified an increased risk of UGIB in homozygous patients (OR: 2.17, CI 95%: 1.01-4.66) (Wu et al., 2016). Finally, Mallah et al. (2020) evaluated three SNPs in the PTGS1 gene (rs1330344, rs384287, and rs5788) and one SNP in the NOS3 gene (rs1799983). ...
... Except for rs1036114, which is an unprecedented analysis, three other studies assessed the influence of rs3842787, rs1330344, and rs5788 on the UGIB risk (van Oijen et al., 2006;Wu et al., 2016;Mallah et al., 2020). In line with our findings, Mallah and colleagues suggested that rs1330344 was associated with an increased risk of UGIB in LDA users (Mallah et al., 2020), and Wu and colleagues reported rs1330344 as a possible risk factor for the gastric mucosal injury induced by LDA (Wu et al., 2016),whereas two studies did not identify association between genetic variants rs3842787 and rs5788 and UGIB risk (van Oijen et al., 2006;Wu et al., 2016). ...
Objective: To assess the association between PTGS1 and NOS3 variant alleles and the risk to develop upper gastrointestinal bleeding (UGIB) secondary to complicated peptic disease.
Methods: A case–control study was conducted in a Brazilian complex hospital from July 2016 to March 2020. Case: Patients with UGIB diagnosis. Control: Patients admitted for surgery not related to gastrointestinal disorders. Variables: UGIB (outcome), genetic variants in PTGS1 and NOS3 genes (independent), and sex, age, schooling, ethnicity, previous history of gastrointestinal disorders, Helicobacter pylori serology, comorbidity, drug therapy, and lifestyle (confounding). The single-nucleotide polymorphisms (SNPs) of the PTSG1 gene (rs1330344, rs3842787, rs10306114, and rs5788) and NOS3 gene (rs2070744 and rs1799983) were determined using the real-time polymerase chain reaction. Helicobacter pylori serology was determined through the chemiluminescence technique. Logistic regression models were built and deviations of allelic frequencies from Hardy–Weinberg equilibrium were verified.
Results: 200 cases and 706 controls were recruited. Carriers of the AG genotype of rs10306114 (OR: 2.55, CI 95%: 1.13–5.76) and CA + AA genotypes of rs5788 (OR: 2.53, CI 95%: 1.14–5.59) were associated with an increased risk for the UGIB development. In nonsteroidal anti-inflammatory drugs (NSAIDs) users, the six variants evaluated modified the magnitude of the risk of UGIB, whereas in low-dose aspirin (LDA) users, an increased risk of UGIB was observed for four of them (rs1330344, rs10306114, rs2070744, and rs1799983). Personal ulcer history (p-value: < 0.001); Helicobacter pylori infection (p-value: < 0.011); NSAIDs, LDA, and oral anticoagulant use (p-value: < 0.001); and alcohol intake (p-value: < 0.001) were also identified as independent risk factors for UGIB.
Conclusion: This study presents two unprecedented analyses within the scope of the UGIB (rs10306114 and rs2070744), and our findings showing an increased risk of UGIB in the presence of the genetic variants rs10306114 and rs5788, regardless of the drug exposure. Besides, the presence of the evaluated variants might modify the magnitude of the risk of UGIB in LDA/NSAIDs users. Therefore, our data suggest the need for a personalized therapy and drug use monitoring in order to promote patient safety.
... Regarding population variability, ethnicity and ancestry are important factors that directly influence in the genetic variability among different populations (29,30) . In this context, some studies identified genetic susceptibility to the incidence of NVUGIB secondary to peptic ulcer disease (14,17,18) , as well as for rebleeding episodes (31) . Besides, use of LDA and NSAIDs in patients who have genetic variants in the CYP2C9 (17,32) and VKOCR1 (24) , genes responsible for these drugs metabolism, might lead to an additive interaction and enhance the risks of NVUGIB secondary to peptic disease. ...
Background:
Non-variceal upper gastrointestinal bleeding (NVUGIB) secondary to peptic ulcer disease is a medical digestive emergency and could be one of the most serious adverse drug reactions.
Objective:
To identify the frequency of diagnosis of NVUGIB secondary to peptic ulcer disease.
Methods:
Prospective and epidemiological study conducted in a tertiary referral Brazilian hospital, from July 2016 to December 2019. Upper gastrointestinal endoscopies (UGE) reports were evaluated daily. The diagnosis of NVUGIB secondary to peptic ulcer disease was defined through endoscopic findings of peptic ulcer and erosive gastric lesions, and clinical symptoms. The frequency of diagnosis of NVUGIB secondary to peptic ulcer disease was estimated through the ratio between the number of patients diagnosed and the number of patients underwent UGE in the same period.
Results:
A total of 2,779 endoscopic reports (2,503 patients) were evaluated, and 178 patients were eligible. The total frequency of diagnosis of NVUGIB secondary to peptic ulcer disease was 7.1%. The annual frequency of diagnosis between 2017 and 2019 ranged from 9.3% to 5.7%. Most patients were men (72.8%); self-declared white (71.8%); older people (56.7%); and, had no familiar or personal history of gastrointestinal diseases (60.1%). 90% of the patients had a peptic ulcer and melena (62.8%). Patients made chronic use of low-dose aspirin (29.3%), other antiplatelet agents (21.9%) and, oral anticoagulants (11.2%); and non-steroidal anti-inflammatories use in the week a prior to the onset of clinical symptoms (25.8%).
Conclusion:
Seven in every 100 patients admitted and underwent UGE in a tertiary hospital were diagnosed with NVUGIB secondary to peptic ulcer disease.
... A recent preliminary study by Mallah et al. identified polymorphisms in platelet activity, angiogenesis and inflammatory response genes were associated with aspirinrelated UGIB (Mallah and et al., 2020), building on the findings of previous investigations (Shiotani et al., 2010;Shiotani and et al., 2013;Shiotani et al., 2014;Wu et al., 2016;Cho and et al., 2016;Milanowski et al., 2017). The group identified "positive markers," that indicated an increased risk of aspirin related UGIB and protective "negative markers" which decreased the risk (Mallah and et al., 2020). ...
Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.
... In fact, genetic variations influence patients' reactions to drugs (Madian et al., 2012). Likewise, several lines of evidence indicated a possible association between predisposing genetic factors and gastrointestinal disorders (Shiotani et al., 2013;Shiotani et al., 2014;Wu et al., 2016;Cho et al., 2016;Milanowski et al., 2017). For instance, previous studies associated the genetic variant rs689466 with an increased risk of ulcerative colitis and gastric cancer, and rs2238631 with upper gastrointestinal hemorrhage (UGIH) in aspirin users (Zhang et al., 2011;Andersen et al., 2011;Wu et al., 2016). ...
... Likewise, several lines of evidence indicated a possible association between predisposing genetic factors and gastrointestinal disorders (Shiotani et al., 2013;Shiotani et al., 2014;Wu et al., 2016;Cho et al., 2016;Milanowski et al., 2017). For instance, previous studies associated the genetic variant rs689466 with an increased risk of ulcerative colitis and gastric cancer, and rs2238631 with upper gastrointestinal hemorrhage (UGIH) in aspirin users (Zhang et al., 2011;Andersen et al., 2011;Wu et al., 2016). ...
... In specific, it was suggested that single-nucleotide polymorphisms (SNPs) mainly those present in genes involved in drug metabolism, platelet activation and inflammatory response, might increase the risk of gastrointestinal bleeding in users of low-dose aspirin (Shiotani et al., 2010). However, the studies were limited by their small sample size and by the assessment of exposed cases, exclusively (Shiotani et al., 2013;Shiotani et al., 2014;Wu et al., 2016;Cho et al., 2016;Milanowski et al., 2017). The non-inclusion of individuals unexposed to aspirin in the design of these studies made it impossible to assess the direct effect of genetic polymorphisms on gastrointestinal bleeding. ...
Background
Despite the wide benefits of aspirin and its cost-effectiveness, aspirin prescriptions have been reduced due to idiosyncratic responses in susceptible individuals. Low-dose aspirin and single-nucleotide polymorphisms (SNPs) are independently associated with increased risk of gastrointestinal hemorrhage; however, to-date, no studies investigated the SNP-aspirin interaction effect on upper gastrointestinal hemorrhage (UGIH). Therefore, we aimed to evaluate the role of 25 SNPs in multiple genes involved in platelet activation, angiogenesis and inflammatory response in aspirin-related UGIH.
Methods
A multicenter, full case–control study was conducted in patients exposed and unexposed to aspirin. Three hundred twenty-six cases diagnosed with UGIH were matched with 748 controls (1:3) by age, gender, health center, and recruitment date. Only adults of European origin were included. Participants were stratified by aspirin exposure and genotype [(Aspirin(−), wild-type), (Aspirin(+), wild-type), (Aspirin(+), genetic variation), (Aspirin(−), genetic variation)]. For each SNP, the Odds Ratio of UGIH and their 95% confidence intervals were estimated in each subgroup by using the generalized linear mixed models for dependent binomial variables. SNP-aspirin interaction effect was estimated through Relative Excess Risk due to Interaction (RERI) measures.
Results
We observed two categories of SNPs that might modify the risk magnitude of UGIH in aspirin consumers. Seven SNPs (rs1387180 A > G, rs2238631 T > C, rs1799964 T > C, rs5050 T > C/T > G, rs689466 T > C, rs1799983 T > A/T > G, and rs7756935 C > A) were “positive modifiers” associated with an excess of risk from aspirin exposure and carrying that genetic variation (1.75 ≤ RERI ≤ 4.95). On the contrary, the following nine SNPs (rs2243086 G > T, rs1131882 G > A, rs4311994 C > T, rs10120688 G > A, rs4251961 T > C, rs3778355 G > C, rs1330344 C > T, rs5275 A > G/A > T, and rs3779647 C > T) were “negative modifiers” and associated with a reduced risk in aspirin users (−2.74 ≤ RERI ≤ −0.95).
Conclusion
This preliminary study suggests that polymorphisms in genes involved in platelets activity, angiogenesis and inflammatory response might modify the risk of aspirin-related UGIH. Further studies with larger sample size and in different populations are needed to confirm our findings. If confirmed, this might have great impact on public health, thanks to aspirin’s prophylactic properties in diseases of high incidence and severity.
... Men experience more stress than women in our society and male gender is a possible clinical risk factor for aspirin-induced gastric mucosal injury which possibly account for the reasons for higher rate of ulceration. [19] However, no significant difference was found in terms of P2 lesions. This finding has led to the recommendation that clinicians should pay attention to ulceration in men to reduce missed lesions. ...
Background/aim:
Magnetically-controlled capsule endoscopy (MCE) is a potential option for the evaluation of gastric diseases in cases that are unsuited for conventional endoscopy, avoiding discomfort, sedation, and related complications. This retrospective study investigated associations between MCE findings and patient gender, age, and inpatient/outpatient status.
Patients and methods:
The data of 580 consecutive patients who underwent MCE from 2015 to 2016 were analyzed. Data included age, gender, indication for MCE, inpatient/outpatient status, overall coverage of gastric anatomical landmarks, and comorbid conditions.
Results:
Compared with outpatients, inpatients had a higher rate of overall significant MCE findings (P = 0.014), polyp (P = 0.03), and ulceration (P = 0.003). MCE findings of the inpatient men and women were similar. Considering all patients, the percentage with ulceration was significantly higher in men than in women (P = 0.004), and men were younger (P < 0.001). Compared with younger patients, those aged ≥60 years had significantly higher rates of overall significant findings, mainly polyp and angiodysplasia.
Conclusions:
Compared with outpatients, the inpatients showed higher overall significant findings. Men undergoing MCE were younger than the women, and more likely to have ulcerations. Older patients, whether outpatient or inpatient, had higher rates of significant findings, mainly polyp and angiodysplasia.
... A previous meta-analysis showed that use of low-dose aspirin is associated with several adverse effects, among which the most clinically relevant are major extracranial bleeding events, especially gastrointestinal bleeding. [9] For secondary prevention of cardiovascular disease, the studies of Western countries collectively proposed that the absolute benefits of aspirin far outweigh its absolute risks of major bleeding events. [7] Individuals with a history of cardiovascular events discontinuing low-dose aspirin are at an increased risk of nonfatal MI compared with those who continue treatment of low-dose aspirin. ...
Background: Aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases for the past few years. However, much attention has been paid to the adverse effects associated with aspirin such as gastrointestinal bleeding. How to weigh the benefits and hazards? The current study aimed to assess the feasibility of a cardiovascular/gastrointestinal risk calculator, AsaRiskCalculator, in predicting gastrointestinal events in Chinese patients with myocardial infarction (MI), determining unique risk factor(s) for gastrointestinal events to be considered in the calculator.
Methods: The MI patients who visited Shapingba District People's Hospital between January 2012 and January 2016 were retrospectively reviewed. Based on gastroscopic data, the patients were divided into two groups: gastrointestinal and nongastrointestinal groups. Demographic and clinical data of the patients were then retrieved for statistical analysis. Univariate and multiple logistic regression analyses were used to identify independent risk factors for gastrointestinal events. The receiver operating characteristic (ROC) curves were used to assess the predictive value of AsaRiskCalculator for gastrointestinal events.
Results: A total of 400 MI patients meeting the eligibility criteria were analyzed, including 94 and 306 in the gastrointestinal and nongastrointestinal groups, respectively. The data showed that age, male gender, predicted gastrointestinal events, and Helicobacter pylori (HP) infection were positively correlated with gastrointestinal events. In multiple logistic regression analysis, predicted gastrointestinal events and HP infection were identified as risk factors for actual gastrointestinal events. HP infection was highly predictive in Chinese patients; the ROC curve indicated an area under the curve of 0.822 (95% confidence interval: 0.774–0.870). The best diagnostic cutoff point of predicted gastrointestinal events was 68.0‰, yielding sensitivity and specificity of 60.6% and 93.1%, respectively, for predicting gastrointestinal events in Chinese patients with MI.
Conclusions: AsaRiskCalculator had a predictive value for gastrointestinal events in Chinese patients with MI. HP infection seemed to be an independent risk factor for gastrointestinal events caused by long-term aspirin treatment in Chinese patients with MI, and it should be included in the risk calculator adapted for Chinese patients.
Gastric mucosal injury is the initial stage of the occurrence and development of gastric diseases. Oxidative stress and ferroptosis caused by the imbalance of redox and iron dynamics in gastric mucosal epithelial cells are present throughout the occurrence and development of gastric mucosal injury. Therefore, the inhibition of oxidative stress and ferroptosis is a potential target for the treatment of the gastric mucosal injury. Xiaojianzhong decoction (XJZ), which consists of six Chinese herbal medicines and extracts, is used for the treatment of diseases related to gastrointestinal mucosal injury; however, its specific mechanism of action has yet to be clarified. In this study, we clarified the protective effect of XJZ on gastric mucosa and revealed its underlying mechanism. We established a gastric mucosal injury model using aspirin and administered XJZ. Furthermore, we systematically evaluated the mucosal injury and examined the expression of genes related to oxidative stress, ferroptosis, and inflammation. The study found that XJZ significantly counteracted aspirin-induced gastric mucosal injury and inhibited oxidative stress and ferroptosis in mice. Upon examining SQSTM1/p62(p62)/Kelch-like ECH-associated protein 1 (Keap1)/Nuclear Factor erythroid 2-Related Factor 2 (Nrf2), a well-known signaling pathway involved in the regulation of oxidative stress and ferroptosis, we found that its activation was significantly inhibited by aspirin treatment and that this signaling pathway was activated after XJZ intervention. Our study suggests that XJZ may inhibit aspirin induced oxidative stress and ferroptosis via the p62/Keap1/Nrf2 signaling pathway, thereby attenuating gastric mucosal injury.
