Journal of Cancer Research
- ISSN: 2578-3726
A. Tavartkiladze, G. Simonia, N. Okrostsvaridze, D. Kasradze, P. Revazishvili, I. Andronikashvili1, M. Maisuradze, L. Tavartkiladze, G. Zumbadze, G. Dundua and A. Dumbadze
Introduction: Chronotherapy, the alignment of treatment with the body›s natural circadian rhythms, has shown promise in optimizing therapeutic efficacy and minimizing side effects in cancer treatment. This study investigates the impact of chronotherapy on melatonin secretion, liver enzyme activity, and clinical outcomes in Hodgkin›s lymphoma patients. The liver, a central organ in energy metabolism, exhibits circadian rhythms that regulate various metabolic processes. By synchronizing chemotherapy administration with these rhythms, we hypothesize that chronotherapy can enhance melatonin secretion, improve liver enzyme activity, and lead to better patient outcomes.
Methods: A total of 38 Hodgkin›s lymphoma patients (Stage IV) were divided into two groups: 19 patients received chronotherapy, while the remaining 19 patients were treated with a standard chemotherapy regimen. Melatonin secretion was measured at six time points (every 4 hours) over a 24-hour period across three chemotherapy cycles. Liver enzyme activity was assessed through biopsies taken from different regions of the liver lobes (central and peripheral) to measure the activity of key enzymes (NAD-isocitrate dehydrogenase, NAD-malate dehydrogenase, succinate dehydrogenase, and NAD-dehydrogenase). Results: The chronotherapy group exhibited significantly higher melatonin levels across all cycles compared to the standard regimen group. At 0 hours, melatonin levels in the chronotherapy group increased from 30 pg/mL in Cycle 1 to 70 pg/mL in Cycle 3, while the standard regimen group showed a modest increase from 20 pg/mL to 30 pg/mL. Statistical analysis using a student’s t-test revealed a p-value of 0.0001, indicating that the differences in melatonin peaks between the two groups are statistically significant. Liver enzyme activity data showed a 55.5% improvement in the chronotherapy group compared to the standard regimen group. Enzyme activities for NAD-isocitrate dehydrogenase, NAD-malate dehydrogenase, succinate dehydrogenase, and NAD-dehydrogenase were significantly higher in both central and peripheral regions of the liver lobes in the chronotherapy group.
Discussion: Higher melatonin levels in the chronotherapy group are attributed to the synchronization of chemotherapy with the body›s circadian rhythms. Melatonin, known for its anti-proliferative, pro-apoptotic, and antioxidant properties, enhances immune function and reduces oxidative stress, contributing to improved therapeutic outcomes. The pronounced peaks in melatonin secretion likely result from enhanced melatonin production or stability over time, providing a protective effect against the cytotoxic impact of chemotherapy.The significant improvement in liver enzyme activity suggests that chronotherapy optimizes liver function by aligning metabolic processes with circadian rhythms. Enhanced activity of mitochondrial enzymes involved in energy production and metabolic regulation underscores the liver›s critical role in maintaining energy homeostasis. The reduction in transaminase activity further indicates improved liver health and function in the chronotherapy group.
Clinical Implications: Chronotherapy›s impact on melatonin secretion and liver enzyme activity translates into better clinical outcomes, including higher survival rates and improved quality of life for Hodgkin›s lymphoma patients. By aligning treatment with circadian rhythms, chronotherapy reduces side effects, enhances drug efficacy, and promotesoverall well-being. The adequate levels of melatonin maintained through chronotherapy support the nervous and endocrine systems, ensuring systemic homeostasis.
Conclusion: This study demonstrates that chronotherapy significantly enhances melatonin secretion and liver enzyme activity, leading to improved therapeutic efficacy and reduced side effects in Hodgkin›s lymphoma patients. These findings highlight the potential of chronotherapy to revolutionize cancer treatment by leveraging the body›s natural circadian rhythms. Further research should explore the underlying mechanisms and broader clinical applications of chronotherapy in oncology.