Radiomodifying action, Pharmacokinetic and Biodistribution of Ethyl 3, 4, 5-trihydroxybenzoate-Implication in development of radiomitigator

Abstract

AbstractEthyl 3, 4, 5-trihydroxybenzoate (GAE) is a major bioactive constituent of Hippophae Rhamnoides L. leaves and extract prepared from H. rhamnoides leaves exhibited radioprotective and pharmacological activity. Radiomodifying properties of polyphenol compounds through free radical neutralizing have been reported earlier. However, to date pharmacokinetic (PK) and biodistribution of polyphenol compounds post 60Co-γ-irradiation (5 Gy) exposure have not been studied yet. The study aims to investigate the radio modifying and inflammatory action, PK and biodistribution of GAE at a radioprotective dose and changes, if any, induced after irradiation. Male C 57 BL/6 mice (28–30 g) were administered GAE (200 mg/kg b.wt) orally 15 minutes post to irradiation. Mice were sacrificed at 15, 30 min, 1,2,4,8 and 24 h. PK and biodistribution of GAE in plasma and tissues were studied. The radiomodifying potential was assessed in terms of mitigating NF-kB activity and SGOT, SGPT, urea and creatinine levels in liver and kidney post irradiation. Our study suggested the potential use of GAE as radiomodifying agent inhibits NF-kB expression and maintains the SGOT 24.10 ± 2.4, SGPT 36.01 ± 6.1 U/l, urea18.16 ± 0.003, and creatinine 1.05 ± 0.04 mg/dL upto 8 h in comparison to irradiated mice. Moreover, in biodistribution studies, showed that GAE crosses the blood-brain barrier and is found in brain tissue. Plasma level of GAE peaked at about 15 min, with Cmax 4390.85 ± 285.20 in GAE and in 3391.78 ± 78.13 ng/mL in radiation + GAE-treated animals, Biodistribution resulted in the highest concentration to be found in liver and kidney. These radiomodifying and pharmacokinetic result may be useful for study of the bioactive mechanism associated with radiation injury and to develop a potent formulation of GAE for clinical application.