Glutathione S-transferase as a toxicity indicator in general anesthesia: genetics and biochemical function

Mikstacki, Adam; Zakerska-Banaszak, Oliwia; Skrzypczak-Zielińska, Marzena; Tamowicz, Barbara; Szalata, Marlena; Słomski, Ryszard

doi:10.1016/j.jclinane.2014.07.002

Cited by 12 publications

(6 citation statements)

References 43 publications

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“…Human GST was indicated in numerous studies as a sensitive marker of hepatocellular impairment [ 9 , 22 ]. The enzyme is released from the hepatocytes into the bloodstream if hepatocellular integrity is disrupted.…”

Section: Discussionmentioning

confidence: 99%

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia

Mikstacki¹,

Skrzypczak-Zielińska

Zakerska-Banaszak

et al. 2016

BMC Med Genet

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BackgroundThe serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane.MethodsThe serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated.ResultsThe allele GSTA1*B (−567G, −69T, −52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia.ConclusionsGSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.

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Section: Discussionmentioning

confidence: 99%

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia

Mikstacki¹,

Skrzypczak-Zielińska

Zakerska-Banaszak

et al. 2016

BMC Med Genet

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“…The GST superfamily consists of mitochondrial [one class: κ (K)], microsomal [one class: MGST], and cytosolic [seven classes: α (A), µ (M), ω (O), σ (S), θ (T), π (P) and ζ (Z)] GSTs. GST classes are identified on the basis of sequence similarity, immune cross-reactivity, and substrate specificity [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells

Cheng

Chen

Wen

et al. 2021

IJMS

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Glioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains <30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the activity of chemotherapy drugs. Usually, glutathione S-transferase (GST) superfamily members act as detoxification enzymes by activating xenobiotic metabolites through conjugation with glutathione in healthy cells. However, some overexpressed GSTs not only increase GST activity but also trigger chemotherapy resistance and tumorigenesis-related signaling transductions. Whether GSTM3 is involved in GBM chemoresistance remains unclear. In the current study, we found that T98G, a GBM cell line with pre-existing temozolomide (TMZ) resistance, has high glycolysis and GSTM3 expression. GSTM3 knockdown in T98G decreased glycolysis ability through lactate dehydrogenase A activity reduction. Moreover, it increased TMZ toxicity and decreased invasion ability. Furthermore, we provide next-generation sequencing–based identification of significantly changed messenger RNAs of T98G cells with GSTM3 knockdown for further research. GSTM3 was downregulated in intrinsic TMZ-resistant T98G with a change in the expression levels of some essential glycolysis-related genes. Thus, GSTM3 was associated with glycolysis in chemotherapeutic resistance in T98G cells. Our findings provide new insight into the GSTM3 mechanism in recurring GBM.

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“…GSTs have been recognized as a significant factor related to the clinical outcome of cisplatin-based chemotherapy in patients with NSCLC. The GSTT1, GSTP1 and GSTP1 IIe105Val genes all belong to GST gene family [ 18 ]. In previously published studies, the role of GSTT1, GSTM1, and GSTP1 IIe105Val gene polymorphisms and the clinical outcome of patients with NSCLC treated with chemotherapy have demonstrated that the genetic variability of the GSTM1 and GSTT1 genes are linked to enzyme metabolizing activities [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-Transferase Gene Polymorphisms are Associated with an Improved Treatment Response to Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

et al. 2018

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BackgroundPrevious studies have shown an association with glutathione S-transferase (GST) gene polymorphisms in patients with non-small cell lung cancer (NSCLC) and treatment response. This study aimed to undertake a literature review and meta-analysis of GST gene polymorphisms, including GSTT1, GSTM1, and GSTP1 IIe105Val, and the treatment response to cisplatin-based chemotherapy in patients with NSCLC.Material/MethodsA literature search was undertaken of the main medical publication databases for publications, up to March 2017, on the association between GSTT1, GSTM1, and GSTP1 IIe105Val polymorphisms and the clinical outcome in patients with NSCLC treated with cisplatin-based chemotherapy. A random fixed-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate the associations, considering multiple genetic models. A subgroup analysis according to ethnicity was performed.ResultsTwenty-three published studies were identified that showed that both the null GSTM1 and the GG genotype of GSTP1 IIe105Val were associated with improved treatment response to cisplatin-based chemotherapy (GSTT1 present/null: OR=1.328; 95% CI, 1.074–1.643) (GSTP1 GG + AG vs. AA: OR=0.596; 95% CI, 0.468–0.759). In subgroup analysis, the GSTP1 polymorphism was significantly associated with treatment response in East-Asian patients, but not in Caucasian patients.ConclusionsMeta-analysis showed that the GG genotype of GSTP1 IIe105Val and the null GSTM1 genotype were associated with an improved treatment response to cisplatin-based chemotherapy in patients with NSCLC, especially in East-Asian patients.

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Glutathione S-transferase as a toxicity indicator in general anesthesia: genetics and biochemical function

Cited by 12 publications

References 43 publications

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia

Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells

Glutathione S-Transferase Gene Polymorphisms are Associated with an Improved Treatment Response to Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

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