“Aging” Chemotherapy on Aged Immune System: Protective Effect of a Novel Phytocompound
name of the conference：Strategies for Engineered Negligible Senescence(SENS),Third Conference
venue：Cambridge, England
researcher： F. Marotta, M. Harada, E. Minelli,SK Ono-Nita, P. Marandola
2007/09/6～10/
Aging is associated with a number of well-known immune system impairments which make aged organisms more vulnerable to cancerous, infectious, inflammatory disease and oxidative stress-related diseases. On the other hand, some chemotherapeutic agents are known to have detrimental effects on immunocompetence. The aim of the present study was thus to test a novel phytocompound endowed with antioxidant and immune-regulating properties in an experimental model of antitumor-induced immunosuppression.
Five groups of mice were considered: Y) Young (4-week old) and A) aged (20-month) mice were given intraperitoneally 10 doses of cyclophoshpamide (CTX) (25mg/kg/bw) or CTX plus 150mg/kg/bw of a novelly-constructed and quality-controlled nutraceutical, i.e. DTS (panax pseudo ginseng, eucommia ulmoides, Institute of Health Care Oriental Herbs and Medicine, Tokyo, Japan) (groups: Y-DTS, A-DTS). Untreated young (Y-u) and aged (A-u) mice served as control. After sacrifice, it was determined: macrophage chemo taxis and TNF-α production and serum level of IFN-γ, IL-2 and GM-CSF. Moreover, liver and urinary bladder were examined histologically and for GSH content. No main differences were noted between Y-u and A-u mice. CTX treatment brought about a significant (over 55%, p<0.001)) decrease of macrophage chemotaxis and TNF-α production. It was noted also an over 25% reduction (p<0.001) of all tested cytokine. Such decrements were significantly more marked in A-mice as compared to Y-mice (p<0.05). CTX-induced liver and urinary bladder histological damage together with over 70% decrease of GSH content in both tissue was comparable among Y and A-mice. Co-treatment with DTS proved to significantly restore macrophage function and serum cytokine concentration to untreated control level (p<0.001). DTS partly improved the necro-inflammatory score in the liver and bladder with a nearly 50% improvement of GSH content in both tissues (p<0.05).
Taken together, such preliminary data suggest that DTS effectively prevents CTX-induced immune suppression and oxidative stress which are particularly enhanced in aged mice together with a substantial protection against urotoxicity. This study further prompts an integrative approach in chemotherapeutic strategies especially in old organisms.
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