A Novel Hyaluronic Acid-Glycyrrhizic Acid Complex Mitigates γ-Radiation-Induced Neurotransmitter Damage in Rats

This study presents a novel therapeutic strategy utilizing a hyaluronic acid-glycyrrhizic acid (HLA-GLA) conjugate to counteract γ-radiation-induced neurochemical and systemic damage in rats. Given the increasing medical and occupational exposure to ionizing radiation and the lack of affordable radioprotective agents, the conjugation of GLA with HLA was hypothesized to improve bioavailability and protective efficacy. The HLA-GLA complex was synthesized by coupling aminated GLA to HLA and characterized using GC-MS, FTIR, UV-VIS spectroscopy, and zeta potential analysis. Male Wistar rats received oral doses of GLA or HLA-GLA prior to and following exposure to a single sublethal γ-irradiation dose (6 Gy). Biochemical assessments revealed that HLA-GLA significantly restored brain energy metabolism, increasing ATP and ADP levels by approximately 30% and 35%, respectively, compared to irradiated controls. Furthermore, the conjugate stabilized neurotransmitter levels by markedly improving concentrations of dopamine (DA), norepinephrine (NE), and GABA. Systemic inflammation was effectively suppressed, indicated by reduced CRP, TNF-α, and IL-6 levels. HLA-GLA also provided robust hepato-renal protection, normalizing hepatic enzymes (GPT, GOT) and renal markers (urea, creatinine). Compared to GLA alone, the HLA-GLA conjugate demonstrated superior efficacy in mitigating oxidative stress, inflammation, and metabolic dysregulation, positioning it as a promising, cost-effective candidate for radioprotective intervention.