title: Evaluation of mutagenic effect of two antiobesity drugs on mice's genetic materials.
abstract: Obesity is a complex, multifactorial disease that, similarly to high blood pressure and diabetes, frequently requires pharmacological treatment with long-term use, suggesting that pattern of use could increase the rates of genetic damage. Among antiobesity drugs, meridia and orlistat act with completely different mechanisms of action. This study aimed to evaluate the mutagenic effect of meridia and orlistat on genetic material of mice by cytogenetic analysis, which included the micronucleus test and chromosomal aberration assay at two doses comparable to propose human therapeutic and double therapeutic doses. Results revealed that the total number of structural chromosomal aberrations in bone marrow cells, with gap, was significantly increased for the two drugs at therapeutic doses. The structural chromosomal aberrations involved breaks, gaps, deletions and fragments, and centric fusion. Chromosomal deletions and fragments were the most frequently increased types of structural chromosomal aberrations. At double therapeutic doses, the treated animals showed a high significant increase of total structural chromosomal aberrations with and without gaps for the two drugs. The frequency of micronucleus in mice treated with therapeutic doses was significantly increased for both drugs. The treated animals at double therapeutic doses showed a positive response for both drugs. In conclusion, treatment with these two drugs at therapeutic doses should be taken under precaution and contraindicated at double therapeutic doses, because the cytogenetic analysis of meridia and orlistat showed an adverse effect on genetic materials at therapeutic doses and a mutagenic effect at double therapeutic doses.
authors.affiliation: Cell Biology Department, National Research Center, Cairo, Egypt. selnahta@yahoo.com
authors.forename: Sahar
authors.initials: S
authors.lastname: Ahmed
authors.forename: Inas
authors.initials: I
authors.lastname: Ghaly
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002869:Chromosome Aberrations / Q000139:chemically induced; D003503:Cyclobutanes / Q000008:administration & dosage / Q000633:toxicity*; D020732:Cytogenetic Analysis / Q000379:methods; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D000077403:Orlistat
chemical_list: D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D007783:Lactones; D009153:Mutagens; D000077403:Orlistat; C058254:sibutramine