ROSMARINIC ACID MITIGATES RADIATION-INDUCED THYMIC AND SPLENIC INJURY THROUGH ANTIOXIDANT ENHANCEMENT AND MODULATION OF THYMIC mRNA EXPRESSION IN MICE Authors: Amna Rashid, Rameen Matloob, Khalid Rauf, Muhammad Hassham Hassan Bin Asad, Zia Uddin, Nabi Shah, Ikram Ullah Khan, Muhammad Ikram Journal: Journal of Animal and Plant Sciences (JAPS) ISSN: 1018-7081 (Print), 2309-8694 (Online) Volume: 37 Issue: 1 Year: 2027 DOI: https://doi.org/10.36899/JAPS.2027.1.0013 URL: https://doi.org/https://doi.org/10.36899/JAPS.2027.1.0013 Publisher: Pakistan Agricultural Scientists Forum Abstract:

Ionizing radiation causes significant harm to lymphoid organs through oxidative stress, cellular depletion, and disruption of tissue architecture. The study aimed to establish a sublethal 137Cs γ-radiation-induced model of thymic and splenic injury and to evaluate the mitigating effects of rosmarinic Acid (RA). Total 144 BALB/c mice, 6-8 weeks age and 18-22 g weight, were randomly allocated into six groups: normal control, irradiated control, RA50, RA100, RA150, and levamisole. Mice were exposed to 137Cs γ-radiation to induce thymic and splenic injury and were subsequently treated with RA at doses of 50, 100, 150 mg/kg for 14 days. The mitigating effects of RA were assessed using hematological parameters, thymic and splenic indices, organ cellularity, histological architecture, oxidative-stress and antioxidant markers, and the thymic expression of FoxN1, IL-6, IL-7, and IL-15. At 150 mg/kg dose, thymus and spleen index increased significantly (p ≤ 0.001) from irradiated group. Histological examination showed reduced radiation-associated hypocellularity and architectural disruption in the thymus and spleen, improvement observed at 150 mg/kg. RA significantly reduced malondialdehyde levels in the thymus and spleen (p ≤ 0.001) than irradiated group following treatment with 150mg/kg and significantly improved SOD (p ≤ 0.001), GPx (p ≤ 0.001), CAT (p ≤ 0.01) activity. Furthermore, RA significantly modulated the radiation-altered expression of IL-7 (p ≤ 0.001), IL-6, IL-15, and FoxN1 (p ≤ 0.01) mRNA in the thymus, at 150 mg/kg. Overall, RA, mitigated sublethal radiation-associated thymic and splenic injury, as demonstrated by improvements in hematological and organ indices, oxidative-stress and antioxidant markers, lymphoid tissue architecture, and thymic mRNA expression. These findings suggest that RA may have potential as a natural immunomodulatory agent against radiation-associated lymphoid injury.

Keywords: Thymus, Radiation, Rosmarinic acid, Cytokines, Antioxidant