Cantharidin poisoning has been proven to cause multiple organ damage. Acute circulatory failure, acute renal failure, and multiple organ failure resulting from cantharidin poisoning are the main causes of death for patients with cantharidin poisoning. However, research on the damage of main target organs and mechanism of cantharidin poisoning is not clear. This paper reviews the latest toxicological and pathological research literatures at home and abroad related to cantharidin poisoning and comprehensively summarizes the latest research progress on the toxicological and pathological damage and mechanism of the digestive system, circulatory system, respiratory system, urinary system, reproductive system, skin mucosa, immune system, and nervous system after cantharidin poisoning, to provide reference for improving the molecular toxicological mechanism of cantharidin poisoning and decision-making in the clinical intervention of cantharidin poisoning.
Cantharidin ; Humans ; Poisoning

OBJECTIVE: To determine the combined cytotoxic effect and the molecular basis of triptolide and sodium cantharidinate on hepatoma cell line 7721.
 METHODS: After treating the hepatoma cell line 7721 with triptolide(9, 18, or 36 μg/mL) and/or sodium cantharidinate (2, 5, or 10 μg/mL), cell viability assay and apoptosis were examined by MTT and flocytometry, respectively. The protein levels of caspase 3 and nuclear factor κB were analyzed by Western blot.
 RESULTS: Viability of hepatoma cell line 7721 was inhibited by either the therapy of triptolide and/or sodium cantharidinate (P<0.05) in a time- and dose-dependent manner. The combined effects of both drugs were better than those of the single drug (P<0.05). The combined therapy down-regulated the expression of NF-κB p65 (P<0.05) while up-regulated the expression of caspase-3 (P<0.05).
 CONCLUSION Triptolide and sodium cantharidinate exert a synergistic toxic effect on hepatoma cell line 7721, which is related to increasing capase-3 activity and suppression of NF- κB.
Apoptosis ; drug effects ; Cantharidin ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Caspase 3 ; drug effects ; Cell Line, Tumor ; Diterpenes ; pharmacology ; therapeutic use ; Down-Regulation ; Drug Therapy, Combination ; Epoxy Compounds ; pharmacology ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; NF-kappa B ; drug effects ; Phenanthrenes ; pharmacology ; therapeutic use ; Transcription Factor RelA

OBJECTIVETo investigate the inhibitory effect of compound cantharides capsules on the proliferation of xenografts of human hepatocellular carcinoma HepG(2215) in mice and their mechanism of action.

METHODSOne hundred healthy Balb/c mice (5-week old, male:female 1:1) were used in this study. Mouse models of human HepG(2215) hepatocarcinoma were established. The tumor-bearing mice were divided into five groups randomly. The control group A received daily intragastric administration of physiologic saline. The intervention groups B1, B2 and B3 were treated with compound cantharides capsule in a dose of 12.5 mg×kg(-1)×d(-1), 25 mg×kg(-1)×d(-1) and 37.5 mg×kg(-1)×d(-1), respectively, for 10 consecutive days. The group C had intraperitoneal injection of cyclophosphamide (25 mg×kg(-1)×d(-1)) for 10 consecutive days. The mice were sacrificed after the completion of administration. The tumors were taken out, the tumor volume was measured, the inhibitory rate of body weight was calculated, and the serum AFP concentration and the level of HBV DNA were determined. The survival of each group mice was analyzed. The levels of mRNA expression of apoptosis-related genes were assayed by quantitative RT-PCR. Apoptosis in the tumor cells was assayed with TUNEL staining. Flow cytometry was used to detect the levels of CD3(+), CD19(+), CD4(+) and CD8(+), and microvessel density (MVD) of the tumors was assessed by immunohistochemistry.

RESULTSAfter completion of the treatment, the inhibition rate of tumor growth of the groups B1, B2 and B3 was 29.8%, 38.7% and 48.1%, respectively, and that of the group C was 52.4%, with a significant difference among the groups (P < 0.05). The median survival time of the groups A, B1, B2, B3 and C was (30.0 ± 3.2) days, (49.0 ± 5.1) days, (50.0 ± 5.2) days, (57.5 ± 6.5) days and (49.0 ± 4.7) days, respectively. The median survival time of the group B3 was significantly longer than that of other groups (P < 0.05). The serum AFP level in the groups A, B1, B2, B3 and C was (492.7 ± 48.5) ng/ml, (281.2 ± 25.6) ng/ml, (194.3 ± 18.7) ng/ml, (170.1 ± 15.8) ng/ml and (138.7 ± 12.5) ng/ml, respectively, indicating that it was significantly inhibited in the group C. The inhibition rate of HBV DNA replication of the groups B1, B2, B3 and C was (46.0 ± 5.1)%, (65.5 ± 6.9)%, (81.3 ± 7.8)% and (19.5 ± 2.1)%, respectively, showing that compound cantharides capsules inhibited HBV DNA replication in a dose-dependent manner. The apoptosis rate of the groups A, B1, B2, B3 and C was (0.27 ± 0.03)%, (7.18 ± 2.12)%, (9.17 ± 2.42)%, (11.27 ± 3.03)% and (5.44 ± 2.45)%, respectively, and that of the group B3 was significantly higher than that of the groups A, B1, B2 and C (P < 0.05). The expression level of bax mRNA was significantly higher than that of the group C (P < 0.05). The drug could significantly decrease the bcl-2 mRNA expression level, more remarkably along with the increasing dose of cantharides, and it was significantly lower than that in the group C (P < 0.05). The levels of CD4(+), CD8(+), CD3(+) and CD19(+) were significantly higher than that in the groups A and C (P < 0.05). The value of MVD of the group B3 was significantly lower that that of groups A and C (P < 0.05).

CONCLUSIONCompound cantharides capsules may inhibit the replication of HBV DNA in HepG(2215) cells, inducing apoptosis in the tumor cells, enhancing the immune function to inhibit the growth of liver cancer cells in mice, and significantly prolong the median survival time of tumor-bearing mice.

Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Antiviral Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cantharidin ; administration & dosage ; pharmacology ; Capsules ; DNA Replication ; DNA, Viral ; Drug Combinations ; Female ; Hep G2 Cells ; Hepatitis B virus ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Microvessels ; pathology ; Neoplasm Transplantation ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Tumor Burden ; drug effects ; Virus Replication ; Xenograft Model Antitumor Assays ; alpha-Fetoproteins ; metabolism ; bcl-2-Associated X Protein ; genetics ; metabolism

OBJECTIVESTo establish a HPLC method for determination of N-methylcantharidimide in dogs' plasma and to study the pharmacokinetics of N-methylcantharidimide in dogs'.

METHODThe plasma samples were extracted by methanol. The acetonitrile and the purified water composed mobile phase. The flow rate was 0. 7 mL x min(-1), ultraviolet detection wavelength was at 212 nm.

RESULTThe calibration curve was linear over the range from 0.01-10.0 mg x L(-1) with a correlation coefficiency of 0.996 3. The lower limit of quantitation was 0.01 mg x L(-1). The mean recovery was 92.3%. the relative standard deviation (RSD) of intra-day and inter-day were all less than 10%. After intravenous administration of N-methylcantharidimide with 3 dosages of 10, 15, 20 mg x kg(-1) to dogs, the corresponding distribution half-livers (t1/2alpha) were 1.8, 2.1, 1.7 min, and the elimination half-lives (t1/2beta) were 144,139, 146 min, respectively.

CONCLUSIONThis method is convenient, accurate and reliable. It can be used for determination of N-methylcantharidimide in dogs' plasma and pharmacokinetic studies.

Animals ; Area Under Curve ; Cantharidin ; administration & dosage ; analogs & derivatives ; Chromatography, High Pressure Liquid ; methods ; Dogs ; Female ; Isoindoles ; administration & dosage ; blood ; Male

OBJECTIVETo study the preparation of cantharidin entrapped non-ionic surfactant vesicle (noisome)and evaluate its quality.

METHODThe niosome loaded with cantharidin was prepared using injection method by non-ionic surfactants as the carrier. An centrifugation separation method and HPLC analysis method of the cantharidin were established to detect the entrapment efficiency. The optimum preparation technology was established by a orthogonal experiment. The morphology, and particle size were studied to evaluate the preparation.

RESULTThe average size of niosomes were (209. 8 +/- 0.5) nm. The entrapment efficiency of the CTD-NS was (27.5% +/- 2.0%) and Zeta potential was (41.5 +/- 0.65) mV.

CONCLUSIONThe preparation of cantharidin noisome by TweenA and SpanB is practicable and successful. These experiments can be the basement of developing targeting drug delivery system.

Cantharidin ; administration & dosage ; chemistry ; isolation & purification ; Chromatography, High Pressure Liquid ; Drug Delivery Systems ; Liposomes ; administration & dosage ; chemistry ; Particle Size ; Surface-Active Agents ; administration & dosage

Adult ; Aged ; Cantharidin ; therapeutic use ; Carcinoma, Hepatocellular ; therapy ; Embolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Portal Vein ; Treatment Outcome

The paper summarizes the research progress on the medicinal resources of Mylabris and close origin species in recent years. Besides the 45 species in 7 genus within Meloidae insects which contain cantharidin, there are also more 9 species in 7 close origin genus containing cantharidin which include Zanna, Fulgora and Lycorma within Fulgoridae of Homoptera, Oxocopis, Heliocis Xanthochroa and Oedemera within Oedemeridae of Coleoptera. New medicinal resources of cantharidin are redundant, there are biological relationships in the biosynthesis of cantharidin, the emerge of cantharidin is related to ecology and there is more attention on the new methods of utilizing Mylabris resources such as living body extraction.
Animals ; Antineoplastic Agents ; pharmacology ; Breeding ; Cantharidin ; isolation & purification ; pharmacology ; Coleoptera ; anatomy & histology ; chemistry ; classification ; genetics ; Evolution, Molecular ; Phylogeny

OBJECTIVETo study the pharmacokinetics and bioavailability of cantharidin in beagle dogs to evaluate the pharmacokinetic parameters and bioavailability of cantharidin in beagle dogs by determining dose-time curve and by comparing with the pharmacokinetics of cantharidin injection.

METHODSix beagle dogs, after protein precipitation by hydrochloric acid, ethyl acetate was applied to extract cantharidin from plasma The plasma concentration of cantharidin in beagle dogs was determined by GC-MS. The WinNonLin program was used to calculate the pharmacokinetic parameters and bioavailability.

RESULTThe main pharmacokinetic parameters of cantharidin by iv in dogs (34 mL x h(-1) x kg(-1)) were AUC (203.5 +/- 23.8) h x microg x L(-1), CL (168.8 +/- 18.6) mL x h(-1) x kg(-1), t1/2 (0.69 +/- 0.03) h. The main pharmacokinetic parameters of cantharidin by op (102 microg x kg(-1)) were: AUC (160.4 +/- 26.9) h x microg x L(-1), CL (649.1 +/- 97.7) mL x h(-1) x kg(-1), t1/2 (0.38 +/- 0.1) h., F (bioavailability) = 26.7% comparing to injection.

CONCLUSIONAs compared with cantharidin injection, the absorption of catharidin by op is poor and the bioavailability is also low, indicating that enhancement of the bioavailability will be beneficial to the clinical application.

Animals ; Biological Availability ; Cantharidin ; pharmacokinetics ; Coleoptera ; chemistry ; Dogs ; Male ; Models, Animal

OBJECTIVETo investigate the apoptosis-inducing effect of cantharidin in human lung cancer cells A549 and its molecular mechanisms.

METHODSMTT assay was used to determine A549 cells proliferation. Light and electron microscopy, FACScan, Annexin V-FITC staining and DNA gel electrophoresis were used to detect apoptosis. The expression of bcl-2, Bax and survivin were examined by Western blot.

RESULTSCantharidin inhibited the proliferation of A549 cells. The cells treated with cantharidin showed a typical apoptotic morphology and hypodiploid peak before G(1) phase. Flow cytometry analysis with annexin quantitatively further confirmed the increase of cell apoptosis. DNA of treated A549 cells depicted a ladder pattern characteristic of apoptosis, indicating the presence of DNA fragmentation. Western blot assay showed that cantharidin increased the level of Bax expression and inhibited the level of bcl-2 and survivin expression.

CONCLUSIONCantharidin can induce A549 cells apoptosis mainly via regulation of Bax, bcl-2 and survivin expression.

Adenocarcinoma ; pathology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cantharidin ; pharmacology ; Cell Line, Tumor ; Humans ; Inhibitor of Apoptosis Proteins ; Lung Neoplasms ; pathology ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; bcl-2-Associated X Protein ; biosynthesis ; genetics

Adenosine Triphosphate ; metabolism ; Animals ; Animals, Newborn ; Cantharidin ; pharmacokinetics ; Cell Hypoxia ; drug effects ; Enzyme Inhibitors ; pharmacology ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Flow Cytometry ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Swine