Lymphatic regeneration across an incisional wound: inhibition by dexamethasone and aspirin, and acceleration by a micronized purified flavonoid fraction.
Although the antiinflammatory and antiangiogenic properties of dexamethasone and acetylsalicylic acid have been studied extensively, their effects on lymphangiogenesis in regenerating tissues remain mostly unknown. We studied in rats the pharmacological modulation and the effect of a remote inflammatory stimulus on the lymphatic regeneration upon damage after a surgical procedure. A micronized purified flavonoid fraction bearing antiinflammatory and lymphagogue properties, was also used. An incisional wound and interruption of the afferent lymphatic vessels to the popliteal and axillary lymph nodes of adult rats were made in dorsal thigh and hypochondrium, respectively. The progress of lymphatic regeneration was evaluated 3, 7, 14 and 21 days after surgery. (99m)Tc-dextran lymphoscintigraphy and Evans blue dye uptake were used to evaluate the lymphatic flow and the kinetics of lymphatic regeneration. In control conditions, lymphatic regeneration took 14 days to be accomplished. In the presence of a remote inflammatory response, which conceivably yielded inflammatory mediators to the incised lymphatic vessels, that time was shortened to 7 days. In both conditions, lymphatic regeneration was inhibited by dexamethasone and acetylsalicylic acid and accelerated by the micronized purified flavonoid fraction. These findings indicate that lymphatic regeneration in an incisional wound may be significantly modulated by dexamethasone, aspirin and a micronized purified flavonoid fraction, and these results call our attention for the possibility to pharmacologically stimulate the recovery of a lymphatic failure due to a traumatic event, or to inhibit its function in order to limit the lymphatic spread of cytokines or neoplastic cells.
Greco
Karin Vicente
KV
Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil.
Lara
Pedro Fernandes
PF
Oliveira-Filho
Ricardo Martins
RM
Greco
Rômulo Vicente
RV
Sudo-Hayashi
Lia Siguemi
LS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D003911:Dextrans; D005070:Evans Blue; D005419:Flavonoids / Q000494:pharmacology*; D007202:Indicators and Reagents; D007249:Inflammation / Q000503:physiopathology; D042583:Lymphangiogenesis / Q000187:drug effects*; D008208:Lymphatic System / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D061305:Lymphoscintigraphy; D008297:Male; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D003911:Dextrans; D005419:Flavonoids; D007202:Indicators and Reagents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C034146:technetium Tc 99m dextran; D005070:Evans Blue; D003907:Dexamethasone; D001241:Aspirin