Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice

Abstract

Ionizing radiation (IR) acts as an external stimulating factor, when it acts on the body, it will activate NF-κB and cause the up-regulation of inducible nitric oxide synthase (iNOS) and induce a large amount of nitric oxide (NO) production. NO and other reactive nitrogen and oxygen species (RNS and ROS) can cause damage to biological molecules and affect their physiological functions. Our study investigated the protective role of 2-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-ADT) and 2-acetylamino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-AADT), two nitric oxide synthase inhibitors, against radiation-induced hematopoietic and intestinal injury in mice. Pretreatment with 2-ADT and 2-AADT improved the survival of mice exposed to a lethal dose of radiation, especially, the survival rate of the 2-ADT 20 mg/kg group was significantly higher than that of the vehicle group (p < 0.001). Our findings indicated that the radioprotective actions of 2-ADT and 2-AADT are achieved via accelerating hematopoietic system recovery, decreasing oxidative and nitrosative stress by enhancing the antioxidant defense system and reducing NO as well as peroxynitrite (ONOO−) content, and mitigating the radiation-induced DNA damage evaluated by comet assay. These results suggest that 2-ADT and 2-AADT may have great application potential in ameliorating the damages of radiotherapy.

Radiation-Induced Intestinal Damage: Latest Molecular and Clinical Developments

“…Radiation causes DNA damage, most selectively in rapidly dividing cells that include cancer cells and healthy cells that undergo selfrenewal. Several major studies assessing the effects of ionizing radiation on the GI tissues have been performed in mice (Figure 2) [12,[44][45][46][47][48][49]. In this regard, Du and colleagues recently identified the optimal radiation dose for GI damage studies in Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice [45].…”

“…Given the known ability of ionizing radiation to activate NF-B signaling and increase the levels of inducible nitric oxide synthase and nitric oxide production in GI cells, Kong et al investigated the protective roles of the NOS inhibitors 2-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-ADT, 7) and 2-acetylamino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-AADT, 8) toward RIID in mice [44]. Pretreatment with both compounds via intraperitoneal injection enhanced the survival of mice receiving otherwise lethal radiation doses (7.5 Gy whole body irradiation), with 2-ADT treatment (20 mg/kg) achieving the highest protection.…”

Is it possible to differentiate between 2-phenylaminodihydro-1,3-thiazine from 2-phenyliminotetrahydro-1,3-thiazine by spectral methods? New glance to the old problem

“…The known veterinary preparation among 2-aryl(phenyl)substituted-1,3-thiazines is xylazine (2-(2,6-dimethylphenyl)amino-5,6-dihydro-4H-1,3thiazine), which is used for sedation, anaesthesia, muscle relaxation, and analgesia in animals [9]. Recent paper showed [10], that 2-amino-5,6-dihydro-4H-1,3-thiazine may have great application potential in ameliorating the damage of radiotherapy. Besides, for new derivatives of 2-amino-5,6-dihydro-4H-1,3-thiazine antibacterial, antifungal, and NO synthase inhibiting activities were also found [11][12][13][14][15][16].…”