Protective Effects of Althaea officinalis L. Against Cyclophosphamide-induced Immunosuppression and Bone Marrow/Spleen Injuries in Rats

Background: Chemotherapy targets rapidly dividing cells, impacting HSCs and hematopoiesis. Objectives: We evaluated the protective impacts of Althaea officinalis L. extract (AOE) against cyclophosphamide (CP)- related immunosuppression and damage to the spleen and bone marrow (BM) in rats. Materials and Methods: Sixty Wistar rats were assigned to six groups: a sham group receiving saline, a CP group receiving 100 mg/kg CP for 10 days, co-treatment groups receiving CP and AOE at doses of 250, 500, and 750 mg/kg for 35 days, and an AOE group receiving 750 mg/kg for 35 days. On day 36, rats were euthanized, and blood specimens were collected. Serum antioxidant enzyme levels (catalase, superoxide dismutase, glutathione peroxidase), nitric oxide levels, total antioxidant levels, and lipid peroxidation in spleen tissues were evaluated. Hematological parameters and cytokine levels were evaluated, alongside the expression of pro-apoptotic-related genes (Bcl-2, caspase-3, Bax, p53). Results: AOE treatment significantly reduced IL-6 and IL-1β levels and increased IL-10 levels in a dose-dependent manner (p <0.05). Furthermore, AOE significantly improved antioxidant enzyme activities, increased hematological parameters and decreased NO levels (p <0.05). AOE treatment markedly attenuated pro-apoptotic gene expression and enhanced Bcl-2 levels (p <0.05). Immunohistochemical analysis confirmed a significant reduction in p53-positive cells in AOE-treated groups (p <0.05). Conclusion: AOE enhances hematopoiesis by promoting hematopoietic growth factor production and suppressing inflammatory cytokines, which aids in the proliferation and differentiation of blood cell lineages while reducing apoptosis triggered by CP. The extract’s antioxidant, anti-inflammatory, and anti-apoptotic properties effectively counteract CP’s harmful effects on bone marrow and spleen tissues.