Multifunctional enzymes glutathione transferases (GSTs) are involved in the development of chemoresistance, thus representing a promising target for a novel approach in cancer treatment. This superfamily of polymorphic enzymes exhibits extraordinary substrate promiscuity responsible for detoxification of numerous conventional chemotherapeutics, at the same time regulating signaling pathways involved in cell proliferation and apoptosis. In addition to upregulated GST expression, different cancer cell types have a unique GST signature, enabling targeted selectivity for isoenzyme specific inhibitors and pro-drugs. As a result of extensive research, certain GST inhibitors are already tested in clinical trials. Catalytic properties of GST isoenzymes are also exploited in bio-activation of specific pro-drugs, enabling their targeted accumulation in cancer cells with upregulated expression of the appropriate GST isoenzyme. Moreover, the latest approach to increase specificity in treatment of solid tumors is development of GST pro-drugs that are derivatives of conventional anti-cancer drugs. A future perspective is based on the design of new drugs, which would selectively target GST overexpressing cancers more prone to developing chemoresistance, while decreasing side effects in off-target cells.

Despite evidence that essential hypertension (EH) is a state of increased oxidative stress, the data on oxidative protein modifications is lacking. Besides, the role of extracellular antioxidant enzymes in EH has not been systematically studied. Study was performed in 45 subjects with EH and 25 normotensive controls. Patients were divided into three groups according to the 2003 ESH/ESC guidelines (grade 1-3). Plasma protein reactive carbonyl derivatives (RCD) and SH-groups (as byproducts of oxidative protein damage) as well as antioxidant enzyme activities superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase were studied spectrophotometrically and correlated with blood pressure (BP). RCD levels were increased in EH patients compared to controls and correlated significantly with both systolic blood pressure (SBP) (r ¼ 0.495, Po0.01) and diastolic blood pressure (DBP) (r ¼ 0.534, Po0.01). Plasma SH-groups content was significantly lower in all patients with EH, with no correlation with BP. SOD and catalase activity in patients with grade 1 EH were similar to that of controls. Patients with grade 2 and 3 of EH had lower SOD and catalase activity. However, significant correlation with SBP and DBP was observed for catalase only (r ¼ À0.331; Po0.05 and r ¼ À0.365; Po0.05, respectively). EH patients exhibited higher plasma GPX activity compared to those in controls, and it correlated with SBP (r ¼ 0.328; Po0.05). The results presented show that increased oxidative protein damage is present in all grades of EH. In mild hypertension extracellular antioxidant enzyme activities are not decreased, suggesting they are probably not critical in early EH, but could be important in moderate to severe EH.

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Exposure to potential carcinogens is an etiologic factor for renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the urinary bladder. Cytosolic glutathione S-transferases (GSTs) are a superfamily of enzymes that protect normal cells by catalyzing conjugation reactions of electrophilic compounds, including carcinogens, to glutathione. Some GST enzymes possess antioxidant activity against hydroperoxides. The most well characterized classes have been named alpha (GSTA), mu (GSTM), pi (GSTP) and theta (GSTT); each of these classes contains several different isoenzymes. Several types of allelic variation have been identified within classes, with GSTM1-null, GSTT1-null and GSTP1-Ile105/Ile105 conferring impaired catalytic activity. The effects of GSTM1 and GSTT1 polymorphism on susceptibility to RCC depend on exposure to specific chemicals. Individuals with the GSTM1-null genotype carry a higher risk for TCC. The roles of GSTT1 polymorphism in TCC and GSTP1 polymorphisms in both cancers are still controversial. During kidney cancerization, expression of GSTA isoenzymes tends to decrease, which promotes the pro-oxidant environment necessary for RCC growth. In the malignant phenotype of TCC of the bladder, upregulation of various GST classes occurs. Upregulation of GSTT1 and GSTP1 might have important consequences for TCC growth by providing a reduced cellular environment and inhibition of apoptotic pathways.

According to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.

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