Tamoxifen attenuates postsurgical hindlimb swelling and soft-tissue fibrosis in a rat model of secondary lymphatic injury

Secondary lymphedema is a common complication after lymph node dissection and is characterized by chronic swelling and progressive soft-tissue fibrosis. Tamoxifen has been reported to exert antifibrotic and antioxidant effects. We investigated whether tamoxifen could attenuate postsurgical limb swelling and fibrosis in a rat model of secondary lymphatic injury and explored potential oxidative mechanisms. Forty Wistar-Albino rats were randomized into four groups (n = 10 each). A standardized right hindlimb lymphadenectomy was performed in all groups. Tamoxifen (2.5 mg/kg/day, oral) was administered with different schedules: 7 days preoperative + 7 days postoperative (Group 2), 14 days postoperative starting immediately (Group 3), and 14 days postoperative starting on day 14 (Group 4). Outcomes at day 30 included limb volume change (water volumetry), lymphoscintigraphy (Tc-99 m nanocolloid), histopathological fibrosis score, tissue hydroxyproline, oxidative stress markers, malondialdehyde (MDA) and glutathione (GSH), and selected cytokines. Lymphoscintigraphic parameters did not differ significantly between groups. However, postoperative volumetric increase of the operated limb was significantly greater in untreated controls than in Groups 2 and 3 (p < 0.05). Histopathologic fibrosis scores were significantly lower in Groups 2 and 3 compared to the controls, supported by lower hydroxyproline levels. Tissue MDA levels were higher and GSH levels lower in controls compared with treated groups., suggesting attenuation of oxidative stress by tamoxifen. In this rat model, tamoxifen reduced postsurgical limb swelling and soft-tissue fibrosis, accompanied by lower oxidative stress. However, lymphoscintigraphy did not demonstrate significant between-group differences and a sham-operated control group was not included. Thus, our findings support an antifibrotic/antioxidant effect of tamoxifen on postoperative tissue changes rather than lymphedema prevention.