Radioprotection by copper and zinc complexes of 5-aminosalicylic acid: a preliminary study.
The effect of copper and zinc complexes of 5-aminosalicylic acid (hereafter referred to as Cu-5ASA and Zn-5ASA, respectively) against whole-body gamma radiation-induced cytotoxicity was studied in Swiss albino mice. Protection against lethal irradiation was evaluated from 30 day mouse survival (10 Gy) and endogenous spleen colony assay (11 Gy); and against sublethal dose (4 Gy) was assessed from gamma irradiation (RT)-induced formation of micronuclei in the mouse bone marrow 24 h postirradiation. Pretreatment with either Cu-5ASA (2.5-9 mg/kg) or Zn-5ASA (3.5-14 mg/kg) intraperitoneally (i.p.) delayed and reduced percentage mortality in mice exposed to 10 Gy RT. The doses 9 mg/kg for Cu-5ASA and 7 mg/kg for Zn-5ASA were found to be the most effective dose in preventing RT-induced weight loss and reducing percentage mortality. Both the drugs also caused an increase in the endogenous spleen colonies in mouse exposed to 11 Gy RT. At sublethal doses of RT, pretreatment with either Cu-5ASA or Zn-5ASA resulted in a significant decrease in the RT-induced micronucleated polychromatic erythrocytes and normochromatic erythrocytes (MPCEs and MNCEs) and an increase in the ratio of PCE to NCE (P/N), at 24 h postirradiation. These results show that both Cu-5ASA and Zn-5ASA are effective in protecting normal tissues against lethal and sublethal doses of RT. Further pretreatment with either Cu-5ASA or Zn-5ASA enhanced the survival of tumor-bearing mice (Ehrlich's ascites carcinoma) exposed to 7.5 Gy RT. In fact, both the complexes caused an increase in the mean and average survival times (MST and AST) when compared to the irradiated control, suggesting a synergetic effect of these drugs with radiation in causing cytotoxicity to the tumor cells. The data clearly indicate that both Cu-5ASA and Zn-5ASA significantly reduced the deleterious effect of radiation and hence could be useful agents in reducing the side effects of therapeutic radiation.
Department of Pharmacology, College of Pharmaceutical Sciences, Manipal-576 119, India.
S K
SK
Mantena
M K
MK
Unnikrishnan
K
K
Chandrasekharan
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000532:radiotherapy; D003114:Colony-Forming Units Assay; D003300:Copper; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D051379:Mice; D015162:Micronucleus Tests; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D014916:Whole-Body Irradiation / Q000009:adverse effects; D015032:Zinc
D000636:Aminosalicylic Acids; D011837:Radiation-Protective Agents; D003300:Copper; D015032:Zinc