title: Novel oral detoxification of mercury, cadmium, and lead with thiol-modified nanoporous silica.
abstract: We have developed a thiol-modified nanoporous silica material (SH-SAMMS) as an oral therapy for the prevention and treatment of heavy metal poisoning. SH-SAMMS has been reported to be highly efficient at capturing heavy metals in biological fluids and water. Herein, SH-SAMMS was examined for efficacy and safety in both in vitro and in vivo animal models for the oral detoxification of heavy metals. In simulated gastrointestinal fluids, SH-SAMMS had a very high affinity (Kd) for methyl mercury (MeHg(I)), inorganic mercury (Hg(II)), lead (Pb(II)), and cadmium (Cd(II)) and was superior to other SAMMS with carboxylic acid or phosphonic acid ligands or commercially available metal chelating sorbents. SH-SAMMS also effectively removed Hg from biologically digested fish tissue with no effect on most nutritional minerals found in fish. SH-SAMMS could hold Hg(II) and MeHg(I) tightly inside the nanosize pores, thus preventing bacteria from converting them to more absorbable forms. Rats fed a diet containing MeHg(I), Cd(II), and Pb(II) and SH-SAMMS for 2 weeks had blood Hg levels significantly lower than rats fed the metal-rich diet only. Upon cessation of the metal-rich diet, continued administration of SH-SAMMS for 2 weeks facilitated faster and more extensive clearance of Hg than in animals not continued on oral SH-SAMMS. Rats receiving SH-SAMMS also suffered less weight loss as a result of the metal exposure. Retention of Hg and Cd in major organs was lowest in rats fed with SH-SAMMS throughout the entire four weeks. The reduction of blood Pb by SH-SAMMS was significant. SH-SAMMS was safe to intestinal epithelium model (Caco-2) and common intestinal bacteria (Escherichia coli). Altogether, it has great potential as a new oral drug for the treatment of heavy metal poisoning. This new application is enabled by the installation of tailored interfacial chemistry upon nontoxic nanoporous materials.
authors.affiliation: Department of Biomedical Engineering, Oregon Health & Science University (OHSU) , Portland, Oregon, United States.
authors.forename: Thanapon
authors.initials: T
authors.lastname: Sangvanich
authors.forename: Jingga
authors.initials: J
authors.lastname: Morry
authors.forename: Cade
authors.initials: C
authors.lastname: Fox
authors.forename: Worapol
authors.initials: W
authors.lastname: Ngamcherdtrakul
authors.forename: Shaun
authors.initials: S
authors.lastname: Goodyear
authors.forename: David
authors.initials: D
authors.lastname: Castro
authors.forename: Glen E
authors.initials: GE
authors.lastname: Fryxell
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Addleman
authors.forename: Anne O
authors.initials: AO
authors.lastname: Summers
authors.forename: Wassana
authors.initials: W
authors.lastname: Yantasee
mesh_terms: D000327:Adsorption; D000818:Animals; D018938:Caco-2 Cells; D002104:Cadmium / Q000737:chemistry* / Q000633:toxicity; D002614:Chelating Agents / Q000008:administration & dosage* / Q000737:chemistry; D015913:Chelation Therapy / Q000295:instrumentation / Q000379:methods*; D000075322:Heavy Metal Poisoning; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D007700:Kinetics; D007854:Lead / Q000737:chemistry* / Q000633:toxicity; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008628:Mercury / Q000737:chemistry* / Q000633:toxicity; D011041:Poisoning / Q000188:drug therapy*; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D013438:Sulfhydryl Compounds; D002104:Cadmium; D007854:Lead; D012822:Silicon Dioxide; D008628:Mercury