title: Protective effects and mechanisms of curcumin on podophyllotoxin toxicity in vitro and in vivo.
abstract: Podophyllotoxin (POD) is a naturally occurring lignan with pronounced antineoplastic and antiviral properties. POD binds to tubulin and prevents the formation of mitotic spindle. Although cases of overdose or accidental ingestion are quite often, no specific therapy is currently available to treat the POD intoxication. In the current investigation, the protective effects and mechanisms of curcumin (CUR) on podophyllotoxin toxicity were evaluated in vitro and in vivo. The results showed that CUR could protect POD-induced cytotoxicity by recovering the G2/M arrest and decrease the changes of membrane potential and microtubule structure in Vero cells. A significant decrease of mortality rates was observed in Swiss mice treated by intragastrical administration of POD+CUR as compared with POD alone. The POD+CUR group also exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde level but elevated superoxide dismutase and glutathione levels as compared to the POD group. Histological examination of the liver and kidney demonstrated less morphological changes in the treatment of POD+CUR as compared with POD alone. The mechanism of the protective effects might be due to the competitive binding of CUR with POD in the same colchicines binding site as revealed by the tubulin polymerization assay and the molecular docking analysis, and the antioxidant activity against the oxidative stress induced by POD. In summary, both in vitro and in vivo data indicated the promising role of CUR as a protective agent against the POD poisoning.
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Dai
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.forename: Chong-Yi
authors.initials: CY
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Tian
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Wen-Cai
authors.initials: WC
authors.lastname: Ye
authors.forename: Ren-Wang
authors.initials: RW
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D003474:Curcumin / Q000494:pharmacology*; D004347:Drug Interactions; D005434:Flow Cytometry; D006651:Histocytochemistry; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011034:Podophyllotoxin / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms; D014404:Tubulin / Q000378:metabolism*; D014709:Vero Cells
chemical_list: D014404:Tubulin; D003474:Curcumin; D011034:Podophyllotoxin