Protective effects and mechanisms of curcumin on podophyllotoxin toxicity in vitro and in vivo

Journal Article · Sat Dec 01 00:00:00 EST 2012 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2012.10.010· OSTI ID:22215989

Li, Juan; Dai, Cai-Xia; Sun, Hua ^[1]; Jin, Lu ^[1]; Guo, Chong-Yi; Cao, Wei; Wu, Jie; Tian, Hai-Yan ^[1]; Luo, Cheng ^[2]; Ye, Wen-Cai ^[1]; Jiang, Ren-Wang ^[1]

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1. Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China)
2. State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203 (China)

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. Highlights: ► A potential antidote to treat the podophyllotoxin (POD) intoxication is found. ► Curcumin showed promising effects against POD poisoning in vitro and in vivo. ► The mechanisms lie in the antioxidant activity and competitive binding with tubulin.

• OSTI ID: 22215989
• Journal Information: Toxicology and Applied Pharmacology, Vol. 265, Issue 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALANINES
ALKALINE PHOSPHATASE
AMINOTRANSFERASES
ANTIOXIDANTS
BLOOD
COLCHICINE
CREATININE
CURCUMIN
DMSO
EOSIN
GLUTATHIONE
HEMATOXYLIN
IN VITRO
IN VIVO
KIDNEYS
LACTATE DEHYDROGENASE
LIVER
MICE
MORPHOLOGICAL CHANGES
NITROGEN
OXIDATION
PHOSPHATES
SUPEROXIDE DISMUTASE
TETRAZOLIUM
THERAPY
TOXICITY
UREA