Polysaccharide of Atractylodes macrocephala Koidz Alleviates Cyclophosphamide-Induced Thymus Ferroptosis in Gosling

SIMPLE SUMMARY: During the brooding stage, the goslings are susceptible to various stresses, damaging the thymus and decreasing immune function. Ferroptosis is cell death caused by iron-ion-dependent lipid peroxidation, which has been reported to be closely related to organismal immunity. The polysaccharide of Atractylodes macrocephala Koidz (PAMK) has antioxidation and immunomodulatory effects. Therefore, we used CTX to construct an immunosuppression model for goslings to explore the mechanism by which PAMK alleviates cyclophosphamide (CTX)-induced ferroptosis in thymocytes and to provide a basis for a more profound elucidation of the immunomodulatory mechanism of PAMK. It was found that PAMK had a significant alleviating effect on CTX-induced thymus damage and thymocyte ferroptosis in goslings. Therefore, PAMK can be used as a natural alternative to antibiotics as a feed additive for immunomodulatory effects on goslings. ABSTRACT: The present study aimed to explore the mechanism by which PAMK alleviates cyclophosphamide (CTX)-induced ferroptosis in thymocytes. One-day-old goslings were divided into four groups (10 goslings/group). The CON and CTX groups were fed a basic diet. The PAMK and CTX + PAMK groups were fed the basic diet mixed with PAMK (400 mg/kg). Moreover, the CTX and CTX + PAMK groups were given a daily injection of 40 mg/kg BW of CTX (at 19, 20, and 21 days of age). On the other hand, the CON and PAMK groups were given 0.5 mL of sterilized saline into the leg muscle (at 19, 20, and 21 days of age). The goslings were fed for 28 days. The ferroptosis pathway was enriched in transcriptome sequencing. Compared to the CON group, the thymus in the CTX group underwent injury, and the mitochondria of thymocytes showed features of ferroptosis. PAMK treatment alleviated ferroptosis in thymocytes and thymus injury, and CTX-induced elevated levels of oxidative stress and iron content restored GPX4 protein expression (p < 0.05) and inhibited the CTX-induced activation of the ferroptosis pathway (p < 0.05). Conclusively, PAMK could reduce thymus injury by alleviating CTX-induced thymocyte ferroptosis in gosling to alleviate the immunosuppression caused by CTX in the organism.