FIRST DEPARTMENT OF PEDIATRICS, UNIVERSITY OF ATHENS
Contributions
Type: Publication Only
Background
Melatonin, the main hormone secreted by the pineal gland in the human brain, has a strong impact on the sleep-wake cycle and is considered to be the general moderator of circadian rhythm and through this of several biological functions. It has also been shown to neutralize a number of free radicals and to enhance the activity of several antioxidative enzymes. Patients with acute lymphocytic leukemia (ALL) show significantly deranged oxidation homeostasis due to both the leukemic burden and the therapy. Alterations of circadian rhythm of melatonin secretion on these patients either at diagnosis or during therapy could enhance oxidative stress or affect bioavailability and efficacy of therapeutic agents.
Aims
Aim of the present study was to elucidate whether melatonin maintains its diurnal variation among pediatric patients with ALL from diagnosis and throughout their treatment. Additionally, correlation of melatonin’s level with the oxidative/antioxidant status of these patients was also evaluated.
Methods
Twelve patients (median age 6.5 years old) with intermediate risk B-ALL, treated according to BFM-ALL95 protocol, were included in this study. Morning (10 am) and night (10 pm) samples were collected from each patient at 7 different time points, with a median follow up time being 8 months. More precisely, blood samples were collected at the time of diagnosis, at the end of the first part of Induction, at the beginning and at the middle of Consolidation and Reinduction cycles and before starting Maintenance therapy. Melatonin levels were measured in serum by an Enzyme Linked Immunofluorescent Assay (ELISA). Total oxidative stress was estimated by colorimetric assay by measuring the total quantity of lipid peroxides present in serum. Total antioxidative serum capacity was estimated by photometric assay by adding a specific quantity of hydrogen peroxide in the sample and then measuring the remaining amount, not neutralized by the natural antioxidants in the serum.
Results
Melatonin’s secretion retained its circadian rhythmicity with higher levels (9.72 ±7.39 pg/ml) at night and lower during the day (8.1 ±6.19 pg/ml) throughout the study (p <0.05). In this respect, intrapatient AM and PM levels, as well as their difference were stable. Total Oxidative Capacity showed an inverse circadian rhythm pattern with higher levels measured in the morning (612.79 ±329.56 μmol/L) and lower in the night (531.50 ±321.75 μmol/L) samples (p<0.001). Of note the highest levels of oxidative stress (913.30 ±277.26 μmol/L) were measured at the time of diagnosis (p<0.001). This was the time point with the lowest, though not statistically significant, melatonin concentration. Moreover, morning levels of melatonin correlated with the oxidative versus anti-oxidative ratio (r 0.23, p<0.05).
Summary
This study depicts, for the first time to our knowledge in the literature, the daily variations of melatonin and oxidative stress in pediatric patients with ALL. Our results showed that melatonin levels maintain their circadian rhythm in our pediatric patients with ALL, both at diagnosis and throughout treatment. Furthermore, we portrayed that oxidative capacity exhibited a similar inverse circadian rhythm, also retained throughout the study. However, oxidative status presented significant fluctuations between distinct measurements, probably related to leukemic burden and the type and intensity of therapy. The above data are of significant importance as many physiological processes, like hormonal secretion and pharmacodynamics, are affected by the body’s circadian rhythms.
Keyword(s): Antioxidants, B cell acute lymphoblastic leukemia, Chemotherapy toxicity, Pediatric
Session topic: Publication Only
Type: Publication Only
Background
Melatonin, the main hormone secreted by the pineal gland in the human brain, has a strong impact on the sleep-wake cycle and is considered to be the general moderator of circadian rhythm and through this of several biological functions. It has also been shown to neutralize a number of free radicals and to enhance the activity of several antioxidative enzymes. Patients with acute lymphocytic leukemia (ALL) show significantly deranged oxidation homeostasis due to both the leukemic burden and the therapy. Alterations of circadian rhythm of melatonin secretion on these patients either at diagnosis or during therapy could enhance oxidative stress or affect bioavailability and efficacy of therapeutic agents.
Aims
Aim of the present study was to elucidate whether melatonin maintains its diurnal variation among pediatric patients with ALL from diagnosis and throughout their treatment. Additionally, correlation of melatonin’s level with the oxidative/antioxidant status of these patients was also evaluated.
Methods
Twelve patients (median age 6.5 years old) with intermediate risk B-ALL, treated according to BFM-ALL95 protocol, were included in this study. Morning (10 am) and night (10 pm) samples were collected from each patient at 7 different time points, with a median follow up time being 8 months. More precisely, blood samples were collected at the time of diagnosis, at the end of the first part of Induction, at the beginning and at the middle of Consolidation and Reinduction cycles and before starting Maintenance therapy. Melatonin levels were measured in serum by an Enzyme Linked Immunofluorescent Assay (ELISA). Total oxidative stress was estimated by colorimetric assay by measuring the total quantity of lipid peroxides present in serum. Total antioxidative serum capacity was estimated by photometric assay by adding a specific quantity of hydrogen peroxide in the sample and then measuring the remaining amount, not neutralized by the natural antioxidants in the serum.
Results
Melatonin’s secretion retained its circadian rhythmicity with higher levels (9.72 ±7.39 pg/ml) at night and lower during the day (8.1 ±6.19 pg/ml) throughout the study (p <0.05). In this respect, intrapatient AM and PM levels, as well as their difference were stable. Total Oxidative Capacity showed an inverse circadian rhythm pattern with higher levels measured in the morning (612.79 ±329.56 μmol/L) and lower in the night (531.50 ±321.75 μmol/L) samples (p<0.001). Of note the highest levels of oxidative stress (913.30 ±277.26 μmol/L) were measured at the time of diagnosis (p<0.001). This was the time point with the lowest, though not statistically significant, melatonin concentration. Moreover, morning levels of melatonin correlated with the oxidative versus anti-oxidative ratio (r 0.23, p<0.05).
Summary
This study depicts, for the first time to our knowledge in the literature, the daily variations of melatonin and oxidative stress in pediatric patients with ALL. Our results showed that melatonin levels maintain their circadian rhythm in our pediatric patients with ALL, both at diagnosis and throughout treatment. Furthermore, we portrayed that oxidative capacity exhibited a similar inverse circadian rhythm, also retained throughout the study. However, oxidative status presented significant fluctuations between distinct measurements, probably related to leukemic burden and the type and intensity of therapy. The above data are of significant importance as many physiological processes, like hormonal secretion and pharmacodynamics, are affected by the body’s circadian rhythms.
Keyword(s): Antioxidants, B cell acute lymphoblastic leukemia, Chemotherapy toxicity, Pediatric
Session topic: Publication Only