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PubMed1985

The treatment of Fasciolopsis buski infection in children: a comparison of thiabendazole, mebendazole, levamisole, pyrantel pamoate, hexylresorcinol and tetrachloroethylene.

Four relatively new broad spectrum anthelmintics (thiabendazole, mebendazole, levamisole and pyrantel pamoate) were compared with two older anthelmintics, (tetrachloroethylene and hexylresorcinol) to treat heavy Fasciolopis buski infections in 17 children aged 4-13 years in hospital. Tetrachloroethylene was the most effective drug in these 17 children and another 49. Large numbers of worms were expelled and faecal egg counts were markedly reduced (99%). The mean number of worms per child was 122 with a range of 7 to 818. All the other anthelmintics tested were ineffective; no worms or only a few were expelled after treatment. However, the oral administration of tetrachloroethylene and hexylresorcinol were associated with severe anaphylactic reactions which were prevented by prior treatment with antihistamines.

Adolescent↗

PubMed1987

An intervention study using thiabendazole suspension against Strongyloides fuelleborni-like infections in Papua New Guinea.

In an isolated rural community in Papua New Guinea, 88 children were found to be infected with Strongyloides cf. fuelleborni; 50 of these also had hookworm infections. Their ages ranged from one to 124 months and all were treated with thiabendazole suspension, 25 mg/kg twice daily for 3 days. 2 patients with Strongyloides and 5 with hookworm were still passing ova 2 weeks after treatment although their egg counts were lower or the same as the pre-treatment counts. 26 children experienced some side effects from the drug, vomiting being the most common; in none did side effects prevent completion of therapy. No association between Strongyloides egg load and nutritional status, hepatosplenomegaly, respiratory ailments, oedema or serum albumin levels was found.

Child↗

PubMed1988

The effects of thiabendazole, mebendazole and cambendazole in normal and immunosuppressed dogs infected with a human strain of Strongyloides stercoralis.

The effects of three benzimidazole anthelmintics in dogs infected with a human strain of Strongyloides stercoralis were investigated. Cambendazole, but not thiabendazole or mebendazole, abrogated the subsequent development of a patent infection when administered at the same time as infection to immunocompetent dogs. None of the drugs eradicated infection when given after the onset of patency in immunosuppressed animals, although worm burdens were greatly reduced in dogs treated with cambendazole. The implications of these findings for the treatment of patients with strongyloidiasis, particularly those with disseminated infections, are discussed.

Animals↗

PubMedDate not supplied

Treatment of mixed Oesophagostomum and hookworm infection: effect of albendazole, pyrantel pamoate, levamisole and thiabendazole.

Oesophagostomum bifurcum has recently been recognized as a common parasite of man in northern Togo and in Ghana. In a preliminary trial several anthelmintics were evaluated in the treatment of mixed Oesophagostomum and hookworm infections. Diagnosis was based on faecal culture, since the eggs of Oesophagostomum and hookworm cannot be distinguished morphologically. Of the anthelmintics tested, albendazole was most effective against both parasites. Pyrantel pamoate, 2 x 10 mg/kg, was effective against Oesophagostomum but not against hookworm. The cure rates for both parasites were moderate with thiabendazole and poor with levamisole.

Albendazole↗

PubMed1987

Mutagenic bioassay of certain pharmacological drugs. I. Thiabendazole (TBZ).

This report describes the chromosomal damage produced by 2-(4'-thiazolyl)benzimidazole or thiabendazole (TBZ) evaluated by "in vivo" and "in vitro" cytogenetic tests. The doses assayed in adult mice by the sister-chromatid exchange (SCE) and micronucleus tests were: 50, 100 and 200 mg/kg body weight; these are within the range of those used in human antihelminthic treatments. SCE frequency was increased only in the last dose (p less than 0.05). A significant increase of micronucleated cells was shown in the 3 doses assayed (p less than 0.001). A marked increase in abnormal anaphase-telophase cells was only detected with the two highest concentrations assayed (0.60-0.24 microgram/ml) p less than 0.01 and p less than 0.05 respectively. The observed genotoxic effects of this compound indicate that TBZ itself is a mutagenic agent.

Anaphase↗

PubMed1982

Thiabendazole (TBZ), an immunohemomodulator. I. Effects on lymph node and spleen.

Previous studies in our laboratory with Thiabendazole (TBZ) indicated that the drug significantly augmented cellular immune responses in mice. The purpose of the present and companion study was to determine which of the cell populations in primary and secondary lymphoid organs and in bone marrow were affected by the in-vivo administration of TBZ. Two major changes in lymph nodes and/or spleens of TBZ-treated mice were detected by histological and quantitative planimetric analysis: (1) expansion of T and B lymphocyte compartments and (2) increase in extramedullary hemopoiesis. The effect on T cells and on hemopoiesis were observed only when TBZ was administered with the thymus-dependent neoantigen, dinitrofluorobenzene (DNFB). The effect on B cells appeared to be antigen-independent. Increased extramedullary hemopoiesis in TBZ + DNFB-treated mice was preceded by a significant increase in pluripotent hemopoietic stem cell activity in bone marrow, as measured by the CFU-S assay. This study indicates that TBZ has significant effects on the development and differentiation of both lymphoid and hemopoietic cells.

Adjuvants, Immunologic↗

PubMed1984

The maternal-foetal distribution of thiabendazole administered in two different vehicles to pregnant mice.

We have compared the effects of two vehicles on the maternal-foetal distribution of 14C-thiabendazole ([14C]TBZ) given orally to Jcl: ICR mice on day 9 or 16 of gestation. TBZ, either suspended in olive oil (TBZ-O) or in a 0.5% aqueous solution of gum arabic (TBZ-G), was given orally on day 9 of gestation at a dose of 1 g/kg body weight (1 microCi/mouse). The mice were killed 0.5, 1, 3, 6, 12, 24 or 72 hr later. In mice treated with TBZ-O maximum levels of radioactivity in plasma and conceptuses were observed at 0.5 hr, whereas in those treated with TBZ-G maximum 14C levels were observed at 6 hr. The uptake of radioactivity from TBZ-O into the plasma and conceptuses was significantly higher than that from TBZ-G. Only trace levels of radioactivity were detected at 72 hr in both treatment groups. The placental transfer of [14C]TBZ was examined in mice treated with doses of 1 g/kg body weight (1 microCi/mouse) given as TBZ-O or TBZ-G on day 16 of gestation. The radioactivity in foetuses, placentas and maternal plasma was higher in mice treated with TBZ-O than those given TBZ-G. The placental transfer of [14C]TBZ was also examined by whole-body autoradiography in mice treated on day 16 of gestation.

Animals↗

PubMed1984

Teratogenicity of thiabendazole in ICR mice.

Thiabendazole (TBZ) was tested for teratogenicity using Jcl:ICR mice. TBZ suspended in olive oil was given orally to pregnant mice at different stages of organogenesis. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. In mice given 700, 1300 or 2400 mg TBZ/kg body weight/day on days 7-15 of gestation, dose-dependent external and skeletal anomalies, especially cleft palate and fusion of vertebrae, were observed. In mice given a single dose of TBZ (2400 mg/kg) on any one of days 6-13, an increased number of malformations was observed. Various types of malformation occurred, especially in the mice treated on day 9. Reduction deformity of limbs was found in mice given TBZ on days 9-12, a change that has not previously been observed to occur spontaneously in normal ICR mice in our laboratory. In order to determine a dose-response relationship, groups of mice were given one of 17 doses of TBZ (30-2400 mg/kg) on day 9 of gestation. The number of litters having foetuses with reduction deformity of limbs and of those having foetuses with skeletal fusion increased in proportion to the dose of TBZ. The regression lines of Y (probit response) on X (log dose) for reduction deformity of limbs and for skeletal fusion were Y = 2.47X - 3.65 and Y = 1.54X + 0.48, respectively. The effective doses (ED1) for the two malformations were 362.0 and 26.4 mg/kg, respectively.

Animals↗

PubMed1985

Irreversible in vivo binding of thiabendazole to macromolecules in pregnant mice and its relation to teratogenicity.

The binding of [14C]thiabendazole ([14C]TBZ) to macromolecules in the liver, foetus and other tissues was investigated in Jcl:ICR mice on day 13 of gestation. TBZ suspended in olive oil was given orally in a dose of 1 g/kg body weight (5 microCi/mouse) and the mice (in groups of three) were killed 0.5, 1, 3, 6, 24 and 96 hr later. The bound radioactivity in the liver and foetus was at a maximum between 3 and 24 hr after treatment. The rate of decrease of the bound radioactivity was slower than that of total radioactivity. Bound radioactivity was also present in other tissues (including kidney, lung, heart, placenta and spleen). The level of bound radioactivity was measured in the liver and foetuses after oral administration of teratogenic doses of 200-1600 mg/kg. Disproportionate increases in bound radioactivity were observed in both tissues after administration of the highest dose.

Abnormalities, Drug-Induced↗

PubMed1986

Enhancing effect of thiabendazole on urinary bladder carcinogenesis induced by sodium o-phenylphenate in F344 rats.

Sodium o-phenylphenate (OPP-Na), a urinary bladder carcinogen in rats, and another fungicide, thiabendazole (TBZ) were fed separately or simultaneously to F344/DuCrj rats of both sexes. The rats were fed one of six diets, either the basal (control) diet or basal diet containing 0.2% TBZ (group T), 1% OPP-Na (1% SO), 2% OPP-Na (2% SO), 1% OPP-Na plus 0.2% TBZ (1% SO-T) or 2% OPP-Na plus 0.2% TBZ (2% SO-T) for 13 or 65 wk. In the 13-wk study, in which groups of ten rats of each sex were used, urinary bladder tumours appeared in 8/10 males in each of three groups--the 2% SO, 1% SO-T and 2% SO-T groups--but not in the remaining animals. Of these tumours, carcinoma accounted for 3/8 tumours in the 2% SO group, 2/8 in the 1% SO-T group and 8/8 in the 2% SO-T group. In the 65-wk study, in which groups of 15 rats were used, the tumour incidence in males was 1/15 in the T group and 15/15, 12/15 and 14/15 in the 2% SO, 1% SO-T and 2% SO-T groups, respectively, while in the females, tumours were found in 2/15, 1/15 and 12/15 animals in the 2% SO, 1% SO-T and 2% SO-T groups, respectively. Of these tumours, carcinoma accounted for 10/15, 11/12 and 10/14 in the males of the 2% SO, 1% SO-T and 2% SO-T groups, respectively, and for 1/2 and 6/12 in the 2% SO and 2% SO-T females, respectively. The tumour incidences in the 1% SO-T males in the two studies and in the 2% SO-T females in the 65-wk study showed a statistically significant increase over those in the 1% SO males or the 2% SO females. Thus, TBZ apparently enhanced the carcinogenic effects of OPP-Na in the rat urinary bladder.

Animals↗

PubMed1987

Effects of pretreatment with SKF-525A or sodium phenobarbital on thiabendazole-induced teratogenicity in ICR mice.

To study the effects of SKF-525A, an inhibitor of cytochrome P-450, and of sodium phenobarbital (PB), a drug-metabolizing enzyme inducer, on the teratogenicity of thiabendazole (TBZ), pregnant mice were given ip either a single dose of 40 mg SKF-525A/kg 1 hr before oral dosing with 250 or 500 mg TBZ/kg or a dose of 75 mg PB/kg/day on three consecutive days before oral administration of a dose of 500 or 1000 mg TBZ/kg. In either case the TBZ dose was given on day 9 of gestation. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The spectrum of malformations in the groups of mice pretreated with SKF-525A or PB was similar to that in mice treated only with TBZ. In the group pretreated with SKF-525A, however, the incidence of resorbed foetuses was higher than in the group treated with TBZ alone and there was a tendency towards an increase in the number of foetuses with skeletal fusion and reduction deformity of the limbs, an anomaly characteristically induced by TBZ. On the other hand, in mice pretreated with PB, the incidence of resorbed foetuses tended to be lower, the numbers and body weights of live foetuses were higher and the incidence of external and skeletal malformations was lower than in the groups treated with TBZ only. No reduction deformity of the limbs was observed in the groups pretreated with PB. These results suggest that with TBZ the ultimate teratogen may be the parent compound rather than its metabolites.

Abnormalities, Drug-Induced↗

PubMed1989

Glutathione and cysteine enhance and diethylmaleate reduces thiabendazole teratogenicity in mice.

The effects of cysteine (CYS), glutathione (GSH) and diethylmaleate (DM) on the teratogenicity of thiabendazole (TBZ) were investigated. On day 9 of gestation mice were given ip a dose of 0, 50 or 100 mg CYS/kg body weight, or 0, 400 or 800 mg GSH/kg, or 0, 0.05, 0.10, 0.15 or 0.60 DM/kg. One hr later they were dosed orally with 0, 250, 500 or 1000 mg TBZ/kg. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The number of malformed foetuses was increased in mice pretreated with CYS or GSH and was decreased in those pretreated with DM, in comparison with numbers in the corresponding group treated with TBZ alone GSH pretreatment enlarged the area under the curve (AUC) of TBZ and 5-hydroxyTBZ, a representative metabolite, in foetal tissue. DM pretreatment reduced the AUC of TBZ and 5-hydroxyTBZ.

Abnormalities, Drug-Induced↗

PubMed1989

Effects of thiabendazole on the kidneys of ICR mice.

The effects of thiabendazole (TBZ) on the kidneys of male and female Crj:CD-1 (ICR) mice were investigated. The mice were given 0, 250 or 500 mg TBZ/kg body weight/day by gavage (using olive oil as a vehicle) for 1, 3, 5 or 7 days. The 24-hr urine volumes of treated mice were increased, significantly so in male mice given the high dose of TBZ. Protein was present in the urine of both control and treated mice throughout the experiment but electrophoresis of the protein showed the presence of a relatively high-molecular-weight protein in the urine of the treated mice. Levels of serum urea nitrogen were decreased in treated mice, but serum creatinine levels did not differ from those of controls. Relative kidney weights tended to be dose-dependently increased in comparison with the controls. Pathological examination showed that after one dose (at either level) the kidneys of males and females were swollen and white maculae were present. Microscopic examination revealed dilation of the proximal, distal and collecting tubules with flattening and degeneration of the tubular epithelium. Tubular dilation was severe in high-dose male mice. These histological changes paralleled the alterations in the 24-hr urine volume. These data suggested that the increased urine volume may be caused primarily by the prevention of reabsorption of water in the distal and collecting tubules. Electron microscopy revealed the flattening of foot processes of podocytes and oedematous changes in the mesangium of glomeruli in TBZ-treated mice. We conclude that TBZ given by gavage in olive oil affects the kidneys of ICR mice.

Animals↗

PubMed1990

Nephrotoxicity of thiabendazole in mice depleted of glutathione by treatment with DL-buthionine sulphoximine.

Thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ] is widely used as an anthelmintic and a fungicide. TBZ (50-400 mg/kg body weight administered by oral intubation) produced nephrotoxicity in male ICR mice pretreated with an inhibitor of glutathione synthesis, DL-buthionine sulphoximine (BSO; 4 mmol/kg body weight, ip). The toxicity was characterized by increases in kidney: body weight ratio and serum urea nitrogen concentration and by tubular necrosis. The nephrotoxic effects were both dose and time dependent. TBZ in combination with BSO also produced decreases in p-aminohippurate accumulation and acetylation by renal cortical slices. TBZ (up to 1200 mg/kg/body weight) alone resulted in no nephrotoxicity. Administration (ip) of glutathione monomethyl ester, which is readily hydrolysed to glutathione after being transported into cells, completely protected against the toxicity caused by TBZ in combination with BSO; this result suggests that glutathione depletion is a major factor underlying the toxicological interaction between TBZ and BSO. Treatment with three inhibitors of renal microsomal cytochrome P-450-dependent monooxygenases, piperonyl butoxide, methoxsalen and carbon disulphide, all equally prevented the nephrotoxicity of TBZ given in combination with BSO. These results suggest that metabolism of TBZ is a necessary step in TBZ-induced nephrotoxicity in glutathione-depleted mice.

Animals↗

PubMed1991

Chronic oral toxicity and carcinogenicity study of thiabendazole in rats.

The potential toxicity and carcinogenicity of thiabendazole (TBZ) was investigated in F344 rats. TBZ was given in pelleted diets at different dietary levels (0, 0.05, 0.1, 0.2 or 0.4%) to groups of 30 rats of each sex for 104 wk. Throughout the study, a marked decrease in body-weight gain was observed in males and females fed 0.4% TBZ. Transitional cell hyperplasia of the renal pelvis and/or papilla was observed in dosed groups of each sex with significant positive trends. Low incidence of transitional cell papilloma or carcinoma of the urinary system was recorded in the dosed groups. Preputial gland adenoma occurred in males treated with 0.4% TBZ, and the incidence was significantly higher than in controls. There was no clear-cut evidence of the carcinogenic activity of TBZ in the urinary system of male and female rats.

Administration, Oral↗

PubMed1992

Sex difference in the nephrotoxicity of thiabendazole in mice depleted of glutathione by treatment with DL-buthionine sulphoximine.

In ICR mice depleted of glutathione (GSH) by treatment with DL-buthionine sulphoximine (BSO), males were much more susceptible to thiabendazole (TBZ) nephrotoxicity than females. The nephrotoxicity was indicated by increases in relative kidney weight and serum urea nitrogen (SUN) concentration and by a decrease in renal GSH concentration at 24 hr after TBZ administration. The susceptibility of males to TBZ-induced nephrotoxicity was completely eliminated by pretreatment with oestradiol (OD). Castration of male mice also reduced, though not completely, their susceptibility to TBZ nephrotoxicity. In females pretreated with testosterone (TS), the nephrotoxic effect of TBZ was increased to an extent comparable with that in males.

Animals↗

PubMed1992

Acute renal toxicity of thiabendazole (TBZ) in ICR mice.

The acute toxic effects of thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ] on the kidneys of ICR mice were investigated. The mice were given 0, 250, 500 or 1000 mg TBZ/kg body weight by gavage (using olive oil as a vehicle), and the kidneys were subjected to pathological examination at 1, 3, 5 or 24 hr after dosing. Gross findings were slight enlargement and the presence of whitish areas (white maculae) in kidneys of treated mice at 3, 5 or 24 hr after dosing. Histological findings were desquamation of degenerated cells in proximal tubules of treated mice at 1 hr. Dilation of proximal, distal and collecting tubules was apparent in treated mice at 3, 5 and 24 hr. TBZ-induced renal injury was reduced by pretreatment with inducers of the microsomal monooxygenase system (sodium phenobarbital, beta-naphthoflavone and 3-methylcholanthrene) and were enhanced by pretreatment with inhibitors of that system (2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride and piperonyl butoxide). The concentration of TBZ in blood at 1 or 5 hr after dosing was lower in mice pretreated with microsomal monooxygenase system inducers and was higher in those pretreated with the inhibitors, than in those given TBZ alone. These results suggest that TBZ-induced renal injury may be attributable to the parent compound rather than its metabolites. Measurement of organic ion uptake into renal slices revealed significant depression of [1-14C]tetraethylammonium bromide (TEA) uptake in treated mice at 1 or 5 hr, whereas uptake of p-[glycyl-2-3H]aminohippurate (PAH) was not depressed at 1 or 5 hr after dosing. The reduction in uptake of TEA is interpreted as the result of competitive suppression of the tubular transport of TEA by TBZ. TBZ-induced renal injury was reduced by organic cation transport inhibitors [N'-methylnicotinamide (NMN) or thiamine] but not by organic anion transport inhibitor [p-(dipropylsulphamyl)benzoic acid probenecid], suggesting that the reduction of TBZ-induced renal injury is the result of competitive suppression of the tubular transport of TBZ by NMN or thiamine.

Administration, Oral↗

PubMed1993

Developmental toxicity of orally administered thiabendazole in Sprague-Dawley rats and New Zealand white rabbits.

The developmental toxicity of thiabendazole (TBZ) was assessed in studies in New Zealand white rabbits and Sprague-Dawley rats. The doses of TBZ for these studies were based on decreases in maternal weight gain in dose range-finding studies in pregnant females of each species. In rabbits, TBZ was administered orally at doses ranging from 24 to 600 mg/kg body weight/day in two separate studies. In rats, TBZ was administered at doses of 10, 40 or 80 mg/kg body weight/day. In all studies, TBZ was administered daily by gavage in aqueous suspension on gestation days 6 to 17. In the initial rabbit study, weight loss occurred in the 600 mg/kg/day group and weight gain decreased in the 120 mg/kg/day group. In addition, there were four complete litter resorptions and four abortions in the 120 and 600 mg/kg/day groups, respectively. To determine whether these changes (known to occur spontaneously in rabbits) were reproducible, the study was repeated. In this study, decreased maternal weight gain and decreased foetal weights were found at 600 mg TBZ/kg/day, but there was no evidence of selective developmental toxicity. Similarly, in rats TBZ produced decreased maternal weight gain (12 to 26%) associated with slight (5 to 7%) decreases in foetal weights at doses of 30 and 80 mg/kg/day. No changes were found at 10 mg TBZ/kg/day and no evidence of selective developmental toxicity or teratogenicity was found at any dose. On the basis of these results, it is concluded that TBZ is not teratogenic or selectivity foetotoxic in rats or rabbits.

Abnormalities, Drug-Induced↗