title: Tetracycline hydrochloride: A potential clinical drug for radioprotection.
abstract: Radiation exposure in planned scenario necessarily requires radioprotector for protection against radiation injuries in tissues and organs. A large number of potential radioprotectors have been investigated but no approved radioprotector is available. Hence, in quest for radioprotector, repurposing of clinical drug is an approach which aims at finding the radioprotective potential of known drugs so that in case of untoward accident the knowledge could be translated to drug usage. In this study, we have investigated the radical scavenging properties of tetracycline pertaining to radioprotection. Our study suggests that tetracycline hydrochloride efficiently scavenges free radicals in ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays. Hydroxyl radical scavenging assay has demonstrated its ability to scavenge gamma radiation induced free radicals by lowering the formation of malondialdehyde. Radiation causes damage to macromolecules and hence the protection offered by tetracycline hydrochloride to DNA and protein shows its radioprotective potential. Plasmid DNA relaxation study with pBR322 has shown that tetracycline hydrochloride confers dose modification factor (DMF) of 2 and 4 at 100 μM and 250 μM concentration respectively. Tetracycline hydrochloride has also protected bovine serum albumin (BSA) from radiation induced degradation. The ex vivo studies for lipid peroxidation and mitochondrial membrane potential further substantiate our findings. The whole body animal survival study has shown the drug to offer 20% protection at a lethal radiation dose of 9 Gy. This study demonstrates the radioprotective potential of the drug by providing some insight into ex vivo and in vivo efficacy.
authors.affiliation: Division of Radiation Biodosimetry, Institute of Nuclear Medicine & Allied Sciences, Delhi, 110054, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Alok
authors.affiliation: Division of Radiation Biodosimetry, Institute of Nuclear Medicine & Allied Sciences, Delhi, 110054, India. Electronic address: nkcinmas@rediffmail.com.
authors.forename: N K
authors.initials: NK
authors.lastname: Chaudhury
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002417:Cattle; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D005609:Free Radicals / Q000378:metabolism; D005720:Gamma Rays; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D008810:Mice, Inbred C57BL; D059748:Proteolysis / Q000187:drug effects / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013752:Tetracycline / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016166:Free Radical Scavengers; D005609:Free Radicals; D011837:Radiation-Protective Agents; D012710:Serum Albumin, Bovine; D013752:Tetracycline
keywords: DMF; Free radicals; Radiation; Tetracycline hydrochloride