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- TOXICITY OF CYTISINE
- SUBACUTE TOXICITY
Tabex, Cytisine the Effective and Fast product to Stop Smoking!
Quit smoking! Stop smoking with Tabex!
Tabex A Modern And Reliable Method For Giving Up Smoking!
For Clean Lungs And For A Healthy Hearth! Stop Smoking With Tabex!
TOXICITY OF CYTISINE
Tabex was experimentally studied for its toxicological action on different kinds of experimental animals. The acute LD50 toxicity, the subchronic (30 days) and the chronic (80-180 days) toxicity were determined. The acute toxicity was determined on line H albino mice (intravenously, subcutaneously and orally); rats (intraperitoneally, subcutaneously and orally); dogs (subcutaneously and orally).
Table 1 Acute LD50 toxicity in mice, rats and dogs with different nodes of administration
The mice and the rats were divided in groups of six animals and the dogs in groups of 2 animals for each dose used. The behavior of the animals and the lethality were observed daily for 7 days after the drug was applied. All the results obtained were statistically processed according to Litchfield-Wilcoxon’s method. During the experiments the animals received standard food and water ad libitum (Angelova, O.).
During the observation the following toxic symptoms were found: accelerated respiration, clonic and toxic convulsions, motility disturbances in the hind legs, lower muscle tonus. The absorption index in rats was 4.2. In dogs, injected subcutaneously with 4 mg/kg, the changes occurred one hour after the treatment. The animals began vomiting, colonic and tonic convulsions of body and limbs muscles appeared. The movement was slow and phlegmatic. When stimulated by force, they became aggressive. On the following day the animals restored their normal behavior. No lethality was noted. After oral administration of doses of 15-25 mg/kg, the dogs showed no external symptoms of toxicity.
The results of the acute toxicity studies showed that Cytisine was much less toxic than intravenously applied nicotine, but it was more toxic after intraperitoneal and oral administration.
Table 2 Comparison between acute toxicity of Cytisine and nicotine
|Mode of administration|
|1.75 – 2.12||53.6 – 65.0||1.370 – 1.486|
|Time of death||32.0 +/- 0.8||2.42 +/- 0.1||2.86 +/- 0.1|
|sec (28)||min (38)||min (45)|
|Equipotential molar ration||1||1||1|
|7.9 – 10.5||46.6 – 57.5||411-696|
|Time of death||37.2 +/- 3.1||5.32 +/- 0.4||12.7 +/- 0.6|
|sec (36)||min (28)||min (46)|
|Equipotential molar ration||4.75||0.84||0.37|
The experiments for subacute toxicity were carried out on line H albino mice and Wistar rats of both sexes equally, treated orally with aqueous solution of Tabex with the following terms and doses: mice – for 45 days with a dose of 3.3 mg/kg and rats – for 30 days with a dose of 7.6 mg/kg.
The chronic toxicity was studied on Wistar rats and on dogs treated orally with aqueous solution for the rats and substance in the feed – for dogs, at the following terms and doses:
- Rats – for 90 days with doses: 1.36, 0.45, 0.90 mg/kg
- Rats – for 180 days with doses: 0.45, 0.90 mg/kg
- Dogs – for 180 days with doses: 0.45 mg/kg
The control groups of animals were treated with equivalent amounts of water. All the animals received standard feed and water ad libitum. The behavior and lethality of the animals were observed daily. The following clinical-laboratory and pathoanatomical examinations were carried out:
Hb, RBC, WBC, platelets, leukocyte formula, prothrombin index
serum bilirubin, blood sugar, blood urea
albumin and sediment
examination of internal organs
The data obtained were statistically processed according to Student-Fisher’s method.
No changes in the behavior of the experimental animals were observed during the experiment carried out. No changes were likewise noted in the clinical-laboratory indices studied. The pathoanatomical examinations showed a different degree of dystrophic changes in the liver of the mice treated with 3.3 mg/kg and in the dogs treated with 0.45 mg/kg.
The following enzyme indices were examined: transaminases – SGOT and SGPT, and alkaline phosphatase in chronic experiment on white Wistar rats and dogs treated orally with the following doses and terms:
- Rats – for 90 days with a dose of 1.35 mg/kg
- Rats – for 180 days with doses of 0.45 and 0.90 mg/kg
- Dogs – for 180 days with a dose of 0.45 mg/kg
A statistically significant increase of SGOT was found in the group treated with 1.35 mg/kg for 90 days. The SGOT level was twice higher than that of the control group. The results obtained showed hyperenzynemia of SGOT and coincided with the data of Veress and Rengei about the influence of nicotine on the level of this enzyme.
On the basis of the toxicological studies we can make the following conclusions:
- According to Hodge and Sterner’s classification for oral administration to rats, Tabex belongs to the group of strongly toxic drugs with a good absorption index.
- When given orally to rats for 30 and 90 days, Tabex shows no toxic changes in the hemopoiesis and internal organs of the experimental animals.
- When applied orally to mice for 45 days and to rats and dogs for 180 days, Tabex does not cause any toxic changes in the hemopoiesis and in the internal organs, except different degrees of dystrophic changes in the liver.