Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients

Abstract

Oxidative stress has been implicated in the development of several types of cancer, including myelodysplastic syndromes (MDS), as well as in the resistance to treatment. In this work, we assessed the potential of oxidative stress parameters to predict the response to erythropoiesis-stimulating agents (ESAs) in lower-risk MDS patients. To this end, we analyzed the systemic levels of reactive species (peroxides and NO), antioxidant defenses (uric acid, vitamin E, vitamin A, GSH, GSSG, TAS, as well as GPX and GR activities], and oxidative damage (8-OH-dG and MDA) in 66 MDS patients, from those 44 have been treated with ESA. We also calculated the peroxides/TAS and NO/TAS ratios and analyzed the gene expression of levels of the redox regulators, NFE2L2 and KEAP1. We found that patients that respond to ESA treatment showed lower levels of plasma peroxides (p < 0.001), cellular GSH (p < 0.001), and cellular GR activity (p = 0.001) when compared to patients who did not respond to ESA treatment. ESA responders also showed lower levels of peroxides/TAS ratio (p < 0.001) and higher levels of the expression of the NFE2L2 gene (p = 0.001) than those that did not respond to ESA treatment. The levels of plasmatic peroxides shown to be the most accurate biomarker of ESA response, with good sensitivity (80%) and specificity (100%) and is an independent biomarker associated with therapy response. Overall, the present study demonstrated a correlation between oxidative stress levels and the response to ESA treatment in lower-risk MDS patients, with the plasmatic peroxides levels a good predictive biomarker of drug (ESA) response.

Redox profiles of amyotrophic lateral sclerosis lymphoblasts with or without known SOD1 mutations

“…Then, 500 µl cell lysate with 1 mg/ml protein were added to 1.5 mM of 10 mM SDS, 2 ml of ethanol and 2 ml of n‐hexane, and lipids were extracted from the upper phase formed after centrifugation. Vitamin E (vit E) levels were quantified by reverse‐phase HPLC using an analytic column Spherisorb S10w (250 mm × 4.6 mm), eluted at 1.5 ml/min with n‐hexane modified with 0.9% methanol, and detected in a spectrophotometer (Gilson) at 287 nm 61 . The sample volume (20 µl) injected corresponded to 2 µg protein.…”

“…Vitamin E (vit E) levels were quantified by reverse-phase HPLC using an analytic column Spherisorb S10w (250 mm × 4.6 mm), eluted at 1.5 ml/min with n-hexane modified with 0.9% methanol, and detected in a spectrophotometer (Gilson) at 287 nm. 61 The sample volume (20 µl) injected corresponded to 2 µg protein. A calibration curve made with known concentrations of αtocopherol was used to calculate the concentration of vitamin E present in the extracts, and results were expressed as µM.…”

Oxidative stress profiles of lymphoblasts from Amyotrophic Lateral Sclerosis patients with or without known SOD1 mutations

“…Then, 500 µL cell lysate with 1 mg/mL protein were added to 1.5 mM of 10 mM SDS, 2 mL of ethanol and 2 mL of n-hexane, and lipids were extracted from the upper phase formed after centrifugation. Vitamin E (vit E) levels were quantified by reverse-phase HPLC using an analytic column Spherisorb S10w (250 mm × 4.6 mm), eluted at 1.5 mL/min with n-hexane modified with 0.9% methanol, and detected in a spectrophotometer (Gilson, Lewis Center, Ohio, USA) at 287 nm [59]. The sample volume injected (20 µL) corresponded to 2 µg protein.…”

Is 6-Shogaol an Effective Phytochemical for Patients With Lower-risk Myelodysplastic Syndrome? A Narrative Review

“…As such, oxidative stress parameters, such as malondialdehyde, were suggested to be predictive biomarkers for treatment response in lower-risk MDS patients. 55 Hoeks et al 56 followed the progress of 256 lower-risk MDS patients over 3 years and found a progressive increase of malondialdehyde levels in the patients over time. Oxidative stress due to iron toxicity, especially among transfusion-dependent patients, damaged organs and led to inferior outcomes.…”