Tellurium

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: short-term oral

Remarks:

15-day exposure period

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

no information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Pharmacological melioration by Selenium on the toxicity of tellurium in neuroendocrine centre (Pituitary Gland) in male wistar rats: A mechanistic approach

Author:

Khuwaja, G.

Year:

2020

Bibliographic source:

Saudi Pharmaceutical Journal 28 (2020) 630–636

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

30 male Wistar rats were randomly divided them into five groups (6 animals/group). Group-1 was nominated as control group. Group-2 received an intraperitoneal dose of selenium 0.3 mg per kg body wt. Group-3 was administered with tellurium 4.15 mg per kg body wt. Group-4 was given low-dose (L) of both selenium 0.15 and tellurium 2.075, Group-5 was given High-dose (H) of both selenium 0.3 and tellurium 4.15 mg/kg bw orally once in a day. After 15 days of dosing, the behavioral activities- motor co-ordination rotarod and grip strength test were measured. On 16th-day animals were sacrificed and activity of LPO, GSH, caspase-3, caspase-9, GPx, GR, SOD, catalase, and AChE were performed on the pituitary gland as per standard method reported.

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

sodium tellurite

Cas Number:

10102-20-2

Molecular formula:

Na2O3Te

IUPAC Name:

sodium tellurite

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animals were procured from Animal House, run and managed by Jazan University, Jazan KSA
- Weight at study initiation: Rats used weighed 200–250 g

No further details provided.

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on exposure:

No details on exposure provided.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

15 days

Frequency of treatment:

daily

Doses / concentrations

Dose / conc.:

4.15 mg/kg bw/day

Remarks:

corresponding to approx. 2.4 mg Te/kg bw/day

No. of animals per sex per dose:

6 animals/dose group

Control animals:

yes

Details on study design:

animals were randomly divivded into five groups each having six animals:
Group – 1: The Control group.
Group – 2: Selenium high (H) dose (0.3 mg per kg body weight, i.p.)
Group – 3: Tellurium high (H) dose (4.15 mg per kg body weight, oral)
Group – 4: Selenium low (L) dose (0.15 mg per kg body weight, i.p.) and Tellurium low (L) dose (2.075 mg per kg body weight, oral)
Group – 5: Selenium high (H) dose (0.3 mg per kg body weight, i.p.) and Tellurium high (H) dose (4.15 mg per kg body weight, oral)

Examinations

Observations and clinical examinations performed and frequency:

No information provided.

Specific biochemical examinations:

The pituitary glands of each group were homogenized in Tris-HCl buffer (10 mM, pH 7.4) and centrifuged at 3000 rpm at 4 °C to separate the supernatant-1 (S-1). The S-1 was used for LPO, SOD, caspase- 3, and caspase- 9. The remaining S-1 was again centrifuged at 15,000 g for 20 min at 4 °C which yields the post mitochondrial supernatant (PMS) which was used for further biochemical studies, including the assays of GSH, protein , GPx, GR, catalase, and Acetylcholine esterase (AChE).

Neurobehavioural examinations performed and frequency:

After 1 h of the drug administration on the last day (day 15 after start of exposure), the behavioral activities were assessed systematically.
The animals of all groups underwent for the rotarod training, and grip tests training for the duration of five days, before performing the dosing. Further behavioral studies were continued parallel to dosing until the sacrifice of the animals. Both behavior studies were performed at a temperature of 25 ± 2 °C and relative humidity 45–50%. In this study, every behavioral test was executed by the persons completely blind to the experiment. For further details on test procedure please refer to "Any other information on materials and methods".

Sacrifice and (histo)pathology:

On day 16th of the study, we have sacrificed the animal and dissected out the pituitary gland from the brain of the animals of all groups.

Statistics:

The results were expressed as mean ± S.E.M. Statistical analysis named as one-way analysis of variance (ANOVA), followed by Turkey’s-test was carried out for the significance of the data. For statistical analysis of the readings, Origin software was used. The values which had p < 0.05 were considered statistically significant.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Caspase-3 activity and Caspase-9 activity was notably increased (p < 0.001, 128% and 104 %, respectively) in Group-3 i.e. sodium tellurite (high dose) administered group compared to the control Group-1.
There was a significant rise in the content of TBARS (149%) in Group-3, Te(H) administered rats compared to the control Group-1, whereas the GSH level was significantly decreased (50%, p < 0.001) in Group-3 Te(H) administered compared to the control Group-1. Also, GPx, GR, SOD, and Catalase activities were decreased significantly (p < 0.001) in Group-3 Te(H) compared to the control Group-1.

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

The motor coordination was 37.8% decreased in the Group-3 in comparison to the control Group-1.
Group-3 animals showed 44.9% reduced grip strength in comparison to the control group.

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

4.15 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

behaviour (functional findings)

2

Dose descriptor:

NOAEL

Remarks on result:

not determinable because of methodological limitations

Remarks:

a single dose of tellurium was tested

Applicant's summary and conclusion

Conclusions:

Behavioral data indicated that tellurium caused severe behavioral deficits in rats. The reduced neurological dysfunction hampers the motor performance in the pituitary gland of Tellurium treated Group-3 rats in comparison to control Group-1 rats.

Executive summary:

In this study, 30 male rats were randomly divided into 5 groups of 6 animals and dosed orally once a day for 15 consecutive days: Group-1 was nominated as control group. Group-2 received an (intraperitoneal) dose of selenium 0.3 mg/kg bw. Group-3 was administered with tellurium 4.15 mg/kg bw. Group-4 was given low-dose (L) of both selenium 0.15 and tellurium 2.075 mg/kg bw, Group-5 was given High-dose (H) of both selenium 0.3 and tellurium 4.15 mg/kg bw.

After 15 days of dosing, the behavioral activities- motor co-ordination rotarod and grip strength test were measured. On day 16 animals were sacrificed and activity of LPO, GSH, caspase-3, caspase-9, GPx, GR, SOD, catalase, and AChE were performed on the pituitary gland as per standard method reported.

Sodium Tellurite noticeably increased the TBARS content, expression of caspases and AChE enzyme activities while GSH, GPx, SOD, GR, and CAT were decreased in the pituitary gland of male Wistar rats. However, Selenium treatment significantly protects these changes in the pituitary gland.

Rotarod was used to assess the motor performance of animals walk on the rotating drum whereas grip strength measure by string test in Tellurium treated animals. Behavioral data indicated that tellurium caused severe behavioral deficits in rats. The reduced neurological dysfunction hampers the motor performance in the pituitary gland of Tellurium treated Group-3 rats in comparison to control Group-1 rats, whereas Selenium given together with Te significantly protected the behavioral activities.