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PubMed1995

A randomized comparative study of albendazole and thiabendazole in chronic strongyloidiasis.

An open randomized study for comparing the efficacy of albendazole and thiabendazole in chronic strongyloidiasis was done in 1990-1992. All 35 patients with positive stool examinations for Strongyloides stercoralis were divided randomly into two groups. 23 patients (group A) received albendazole (400 mg twice daily for 5 days) and 12 patients (group B) received thiabendazole (1 g twice daily for 5 days). All patients except four patients in group A were admitted in the Hospital for Tropical Diseases for 21 days for monitoring side effects (D0-7) and stool examination (D0, D7, 8, 9, D21, 22, 23). Methods of stool examination included: direct microscopy of saline smear, formalin ether concentration, culture (Harada and Mori method) and larva count (Stool and Sasa method). Cure was defined as negative stool examination done at 21 days after medication by all above methods. The cure rate for group A was 95% (only one failed to clear the parasite at D21) and the cure rate for group B was 100%. But there was no statistical difference between the two. Mild changes of transminases observed in 5/23 patients who received albendazole, but none developed clinical hepatitis.

Adult↗

PubMed1997

[Hepatic transplantation for severe ductopenia related to ingestion of thiabendazole].

We report a case of severe cholestasis and sicca syndrome after thiabendazole administration for Strongyloides stercoralis infection in a 26-year-old patient. Liver biopsy, performed 15 days after the onset of jaundice, revealed a marked paucity of bile ducts, and cholestasis rapidly progressed to biliary cirrhosis. Because of the progression of jaundice and the development of esophageal varices, orthotopic liver transplantation was performed, 18 months after the beginning of disease. The mechanism responsible for thiabendazole-induced biliary injury is unknown. The association between sicca syndrome and biliary disease suggests an immunoallergic mechanism against an antigen which could be common to the biliary, lacrimal and salivary duct epithelium.

Adult↗

PubMed1998

[Cholestatic hepatitis ascribed to the use of thiabendazole].

Two women, aged 27 and 42 years, both born in Surinam and both suffering from heterozygous thalassemia, developed cholestatic hepatitis three and two weeks respectively after the start of a two-day course of thiabendazol for Strongyloides stercoralis infection. Other causes of cholestasis were unlikely in view of the results of blood tests, echography and the endoscopic retrograde cholangiopancreaticography. The symptoms persisted for several months, and the liver function disorders for 7 years and one year, respectively. The incidence of thiabendazole-induced cholestatic hepatitis is unknown, but probably low.

Adult↗

PubMed1976

Thiabendazole: a potential adjuvant in cancer therapy.

This set of experiments was designed to evaluate the effects of thiabendazole (TBZ), a relatively nontoxic thiazole derivative, on the delayed hypersensitivity response of normal mice, tumor-bearing mice, and mice immunosuppressed by radiation and chemotherapy. Normal mice treated with a single intraperitoneal injection (20 mg. per kilogram) of TBZ given on the day of challenge with 2,4 dinitrochlorobenzene (DNCB) had 41 percent greater swelling of the injected foot pad than did control animals. This increased immune reactivity could be transferred with spleen cells from TBZ-treated animals as well as with macrophages incubated in vitro with TBZ. Mice given sublethal radiation (450 r) had almost complete restoration of the delayed hypersensitivity response (90 percent of control) when treated with TBZ. The immunosuppressive effects of Adriamycin also could be reversed in a similar fashion. It is likely that the immune function of more than one population of spleen cells is amplified by TBZ treatment. The observed effects strongly suggest that thiabendazole may have a role as an adjunct in cancer therapy.

Animals↗

PubMed1999

Adsorption and Two-Dimensional Condensation of Thiabendazole at a Mercury/Solution Interface.

The adsorption behavior of the fungicide thiabendazole [2-(4'-thiazolyl) benzimidazole] was studied with out-of-phase ac voltammetry using a hanging mercury drop electrode in 0.3 M KCl solutions at various temperatures and thiabendazole concentrations. A state of "normal" adsorption and a condensed two-dimensional layer at moderately charged and rather negatively charged surfaces, respectively, have been characterized. Copyright 1999 Academic Press.

Journal Article↗

PubMed1991

Specific interaction of benzimidazole anthelmintics with tubulin from developing stages of thiabendazole-susceptible and -resistant Haemonchus contortus.

The low- and high-affinity binding of tritiated benzimidazole anthelmintics (mebendazole and oxibendazole) to tubulin-containing supernatants derived from unembryonated eggs, third stage larvae or adult worms of thiabendazole-susceptible and -resistant strains of Haemonchus contortus were examined and compared. The displacement of these radioligands by unlabelled benzimidazoles (mebendazole, fenbendazole, thiabendazole and oxibendazole) also was examined. The binding affinity, K alpha, and maximum binding, Bmax, for the high-affinity binding were calculated by non-linear least-square iterative curve fitting using a computer programme (LIGAND) based on the exact mathematical model of ligand-receptor interactions. The K alpha was of the same order of magnitude (x 10(7) M-1) for the susceptible and resistant eggs, larvae and worms. Resistance was associated with a loss of high-affinity binding. There was a 2- to 5-fold loss of Bmax by the resistant strain. The eggs showed greater high-affinity binding per milligram of protein than the larvae which, in turn, showed greater high-affinity binding than the adult worms. It was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis that the tubulin content per milligram of protein decreased from egg, through larvae to adult worm. Cross-displacement studies indicated that different benzimidazole drugs interacted with the same receptor (tubulin) and that a rank order of affinity of the benzimidazole drugs could be inferred.

Animals↗

PubMed1976

Topically applied thiabendazole in the treatment of scabies.

Forty patients were treated for scabies with a 10% suspension of thiabendazole applied externally. Thirty-two patients (80%) had a satisfactory response to one course of therapy, while a second course was necessary in six (15%). Two patients (5%) required intralesional injections of triamcinolone diacetate because of persistent scabious nodules.

Administration, Topical↗

PubMed1997

Thiabendazole-induced cytogenetic abnormalities in mouse oocytes.

Of the various classes of human genetic disorders, aneuploidy is the most prevalent. Besides its association with maternal age and its predominant origin during maternal meiosis I, little is known about the etiology of aneuploidy. Although various classes of chemicals have been shown to induce aneuploidy in experimental systems, there is no definitive evidence for the role of chemically induced aneuploidy and adverse human health effects, particularly germ cell effects. Thus, it is important to understand the potential of chemicals for inducing aneuploidy in germ cells. There are conflicting data in the literature about the ability of thiabendazole (TBZ) to induce aneuploidy; therefore, we investigated the potential of TBZ for inducing aneuploidy in oocytes. Superovulated ICR female mice were administered 0, 50, 100, or 150 mg/kg TBZ by intraperitoneal injection. The frequencies and percentages of hyperploid oocytes were 0/472 (0), 2/410 (0.5), 6/ 478 (1.3), and 3/427 (0.7) for control, 50, 100, and 150 mg/kg TBZ, respectively. The difference between controls and the 100 mg/kg dose was statistically significant. Also, the proportions of ovulatory mice and the number of oocytes collected per ovulatory female were reduced in the TBZ groups relative to controls. Based on these results, we conclude that TBZ induces a small, but significant increase in the frequency of aneuploid oocytes at toxic doses that also impair ovulation.

Aneuploidy↗

PubMed2003

Photomutagenicity of thiabendazole, a postharvest fungicide, in bacterial assays.

We investigated the photomutagenicity of thiabendazole (TBZ), a postharvest fungicide commonly used on imported citrus fruits. Using UVA light (320-400 nm), we irradiated bacterial cultures with or without TBZ in a 24-well multiplate. UVA-irradiation without TBZ was not mutagenic to the tester strains, nor was unirradiated TBZ. TBZ was strongly photomutagenic in Escherichia coli WP2uvrA and WP2uvrA/pKM101 strains, weakly photomutagenic in Salmonella typhimurium TA100 and TA98, and not photomutagenic in S. typhimurium TA1535 and TA1538. The photomutagenicity of TBZ was more evident in WP2uvrA/pKM101, which carries the trpE65 ochre mutation (TAA), than in TA100, which carries the hisG46 missense mutation (CCC). In E. coli WP3101-WP3106 and the corresponding pKM101-containing strains, photoactivated TBZ induced predominantly G:C-->A:T transitions and A:T-->T:A transversions. In the plasmid-containing strains only, TBZ induced a moderate number of A:T-->G:C transitions and a few A:T-->C:G and G:C-->T:A transversions. The observation that UVA-irradiated TBZ mutated both G:C and A:T basepairs may explain why WP2uvrA/pKM101 was more sensitive to its mutagenicity than TA100. TBZ that was irradiated before it was added to the WP2uvrA/pKM101 cells was not photomutagenic, which suggests that the photomutagenic products of TBZ were unstable or rapidly reacted with other molecules before being incorporated into cells.

Antinematodal Agents↗

PubMed1985

In vivo inhibition of adenosine triphosphate (ATP) synthesis associated with thiabendazole-induced teratogenesis in mice and rats.

Ogata et al. (1984) reported that thiabendazole (TBZ) was teratogenic in mice when olive oil was used as a vehicle, but not teratogenic when administered in gum arabic. Results of investigations into the possible association between TBZ-induced teratogenicity and adenosine triphosphate (ATP) are reported here. ATP levels in the limb buds were measured at day 10 of gestation in controls and mice treated with 1300 mg/kg TBZ 24 h previously. The results showed that there was a correlation between the dosage of TBZ and the ATP levels of fore and hind limb buds (r = -0.827 and r = -0.799, respectively). ATP levels in mouse limbs were reduced to 22-31% of control values when TBZ was given in olive oil, but the ATP reduction was only 6-9% when TBZ was given in gum arabic. This suggests that there may be a relationship between the teratogenic and ATP-depressing action of TBZ on the limb buds of mouse embryos. Pregnant rats were also treated with TBZ. TBZ at a dose level of 1000 mg/kg was given orally on day 11 of gestation. After 24 h, ATP levels in fetal rat limbs were still 82% of control values. These results confirm the observations of Ogata et al. on the vehicle effect and the difference in response between mice and rats.

Adenosine Triphosphate↗

PubMed1981

Strongyloides stercoralis hyperinfection: sequential changes of gastrointestinal radiology after treatment with thiabendazole.

Sequential changes of gastrointestinal radiology are described in a case of Strongyloides stercoralis hyperinfection. Duodenal dilatation, reflux of barium into the biliary and pancreatic duct, and mucosal thickening of the small intestine were the striking features before treatment. Although treatment with thiabendazole led to rapid and complete clearance of rhabditiform larvae, some abnormal radiologic changes in the small intestine persisted for approximately 4 months before the mucosal pattern reverted to normal.

Female↗

PubMed1977

Anticonvulsant action of thiabendazole.

Thiabendazole was found to be specifically effective against maximal electroshock seizures in albino rats. It produced a significant dose-dependent decrease in the duration of the tonic extensor phase of hind legs. The ED50 was similar for oral or s.c. administration. PTZ-induced convulsions were unaffected by lower doses but aggravated by the higher dose studied.

Animals↗

PubMed1987

Progressive bile duct injury after thiabendazole administration.

A 27-yr-old man developed jaundice 2 wk after exposure to thiabendazole. Cholestasis persisted for 3 yr, at which time a liver transplant was performed. Two liver biopsy specimens and the hepatectomy specimen were remarkable for almost complete disappearance of interlobular bile ducts. Prominent fibrosis and hepatocellular regeneration were also present; however, the lobular architecture was preserved. This case represents an example of "idiosyncratic" drug-induced liver damage in which the primary target of injury is the bile duct. An autoimmune pathogenesis of the bile duct destruction is suggested.

Adult↗

PubMed1989

Selection for thiabendazole resistance in Ostertagia spp. by low efficiency anthelmintic treatment.

Thiabendazole (TBZ) treatment of grazing weaners infected with a predominantly susceptible strain of Ostertagia reduced worm burdens by 90%. The surviving sub population had a level of resistance four times greater than the original population when compared to similarly infected, but untreated, weaners. TBZ treated and control weaners were relocated to worm-free pasture so that the contamination on the plots grazed by TBZ treated weaners was from the survivors of the drench. The anthelmintic treated groups were subsequently managed under a two summer drench programme while control groups remained so throughout the experiment. Monitoring both parasite population size and the degree of resistance over the following 2 years indicated that after three anthelmintic treatments, resistance developed to a level where TBZ was ineffective. When compared to control groups, a mean reduction in population size of around 80% was maintained in the TBZ treated groups for 1 year. This difference, however, disappeared by the second year. A similar study over 1 year with a moderately TBZ resistant strain of Ostertagia indicated that TBZ treatment produced no significant reduction in population size but more than doubled the level of resistance. The study indicated the critical need for highly efficient anthelmintic treatment, particularly in situations where, through ecology or management, post treatment contamination is likely to contribute substantially to future generations of worms.

Animals↗

PubMed1995

Physiology of two strains of Trichostrongylus colubriformis resistant and susceptible to thiabendazole and mucosal response of experimentally infected rabbits.

Two strains of Trichostrongylus colubriformis of ovine origin, one resistant and one susceptible to thiabendazole, were compared during experimental infection in rabbits. Groups of rabbits were infected with 5000 infective larvae (L3) of either the resistant or the susceptible strain. On days 21 and 42 post-infection (p.i.), 5 rabbits of each group were killed and the small intestine divided into three sections for worm counts and histological or biochemical analysis. Faecal egg counts were performed twice a week from day 15 to day 42 p.i. The physiology of the worms was characterised by in vitro acetylcholinesterase secretion of adult worms. The host inflammatory response was determined by peroxidase activity in mucosal homogenates and by histological counts of mast cells and eosinophils. Infectivity was not significantly different between the two strains. However, egg production was delayed and was significantly lower for the resistant strain. Conversely, in vitro secretion of resistant worms was significantly higher than the susceptible ones. The mucosal homogenetates of rabbits infected with the resistant strain had significantly higher levels of peroxidase activity in the duodenum on days 21 and 42 p.i. Mast cell counts were also significantly higher in the duodenum on day 42 p.i., in rabbits infected with the resistant strain. No difference was observed in the eosinophil counts. These results suggest that genetic variation in the nematode, such as anthelminthic resistance, is associated with variations in worm biology and physiology as well as differences in the inflammatory response of the host.

Acetylcholinesterase↗

PubMed1995

Murine strongyloidiasis: the effects of cyclosporin A and thiabendazole administered singly and in combination.

A single Cyclosporin A (CsA) dose of 30 mg kg-1 given orally at day 4 post-infection (p.i.) to Sprague-Dawley rats infected with Strongyloides ratti, reduced the faecal larval count by 46.8 +/- 1.2%. CsA was equally effective when the same dose rate was administered subcutaneously at day 4 p.i., reducing the faecal larval count by 41.6 +/- 8.6%. Thiabendazole (TBZ) given orally at 5 or 10 mg kg-1 (single dose at day 4 p.i.) reduced the faecal larval counts by 57.1 +/- 4.1% and 69.0 +/- 9.6%, respectively. Orally administered CsA was less effective than 5 mg TBZ kg-1 (at day 4 p.i.) Co-administration of 5 mg TBZ kg-1 and CsA did not elicit synergy or additive efficacy, indicating that CsA did not antagonise the anti-strongyloides activity of TBZ. The data suggests that for patients with current, historical or serological evidence of strongyloidiasis, CsA may be used where immunosuppressive therapy is required for other concurrent reasons or when TBZ is contraindicated.

Administration, Oral↗

PubMed1995

The effect of electron transport (ET) inhibitors and thiabendazole on the fumarate reductase (FR) and succinate dehydrogenase (SDH) of Strongyloides ratti infective (L3) larvae.

The fumarate reductase (FR) and succinate dehydrogenase (SDH) activities of isolated submitochondrial particles (SMPs) prepared from axenised L3 larvae of S. ratti were characterised with respect to their response to a selected range of inhibitors. Rotenone (a specific inhibitor of electron transport Complex I) inhibited the S. ratti FR (EC50 = 3.0 x 10(-7) M) but not SDH. This strongly suggests that the S. ratti FR is functionally linked with the S. ratti ET-Complex I. 2-Thenoyltrifluoroacetone (TTFA, an inhibitor of ET-Complex II) inhibited FR (EC50 = 2.6 x 10(-5) M) and SDH (EC50 = 2.8 x 10(-5) M) with similar effectiveness. Sodium malonate (substrate analogue of succinate) had a greater affinity for SDH (EC50 = 6.8 x 10(-4) M), than FR (EC50 = 1.9 x 10(-2) M). Sodium fumarate was ca. 8-fold more effective in inhibiting the S. ratti FR (EC50 = 6.0 x 10(-4) M) than SDH (EC50 = 4.8 x 10(-3) M). The S. ratti FR was more sensitive to inhibition by thiabendazole (TBZ; EC50 = 4.6 x 10(-4) M) than SDH (EC50 > 1.0 x 10(-3) M), suggesting that one of the sites-of-action of TBZ to be the FR of S. ratti mitochondria. More potent inhibitors of S. ratti FR, if developed, may prove to be effective chemotherapeutic agents in the management of human strongloidiasis.

Animals↗

PubMed1995

Cytotoxic effects of postharvest fungicides, ortho-phenylphenol, thiabendazole and imazalil, on isolated rat hepatocytes.

The cytotoxic effects of ortho-phenylphenol (OPP), imazalil (IMZ) and thiabendazole (TBZ) on isolated rat hepatocytes were investigated. Addition of IMZ and OPP to hepatocyte suspensions at a concentration of 0.75 mM resulted in acute cell death, accompanied by depletion of intracellular levels of glutathione and protein thiols. Both compounds rapidly depleted cellular ATP which consistently preceded the cell death. In addition, the cell death caused by IMZ was accompanied by the accumulation of intracellular malondialdehyde, indicating initiation of lipid peroxidation. During a 3-hr incubation period, TBZ did not affect these parameters. In mitochondria isolated from rat liver, IMZ and OPP impaired respiration related to oxidative phosphorylation. Based on these results, the order of toxic potency is IMZ > OPP > TBZ.

Animals↗