Animal studies on Ukrain

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Studies on anti-cancer effect
Effect on HA-1 hepatoma in mice
Treatment by antitumor drug Ukraine increased life span of mice with HA-1 hepatoma (transplanted intravenously), decreased the increment of tumor weight. In the abdominal fluid such treatment caused a decrease of number of tumor cells and an increase of number of macrophages. Ukrain increased cystatin C level, revealing protective mechanism of action. Another study also showed similar results.

Multiple effects on mice
A marked progressive anticancer and antimetastatic effect was observed on Lewis carcinoma in mice. The antimetastatic effect of the drug manifested as a decrease in both number and volume of lung metastases. Ukrain also made an increase in the endocrine function of the thymus (a central organ of the immune system), an increase in serum interferon, adhesion of
peritoneal macrophages and formation of antibodies against thymus-dependent antigen by spleen plasma cells. It increased the number of lymphoid cells and monocytes in peripheral blood. In addition to the increase in lymphocytes, the number of large granular lymphocytes also increased,
i.e., cells possessing natural cytotoxic activity.

Effect on rat hepatosarcoma
Both Ukrain and the cancer drug Cyclophosphamide were able to induce signs of Apoptosis in a cell culture consisting of liver cancer cells from rats.

Effect on sarcoma-45 in rats
The effect of Ukrain on the growth kinetics of the experimental tumor sarcoma-45 in rats was studied. Ukrain was proved to be an effective antitumor agent on biological and mathematical models in accordance with standardized instructions for screening.
Selective uptake in tumor tissue in rats?
Ukrain penetrates into tissues after injection in labaratory rats by active transport or by favored diffusion. A relatively higher affinity for Ukrain was observed in tumor tissue and liver, while affinity was lowest in the brain and muscles. The presence of tumors decreased Ukrain concentrations in plasma and normal tissues in comparison with those in control animals.

Effect on breast cancer in mice
Intravenous, but not subcutaneous or intraperitoneal, administration of Ukrain
was found to be effective in delaying tumour growth in an actual therapeutic
protocol initiated five days after tumour implantation on mice. No untoward side-effects
were observed. Ukrain induced the activation of tumouricidal function of white blood cells from the abdominal cavity(peritoneum) from tumour bearing but not from normal mice.

Radioprotective effects
Radioprotective effects on the glucocorticoid and thyroid systems in rats
Ukrain minimized the consequences of radiation therapy on parts of the endocrine system in rats.
Two hundred and sixty rats were infected by tularemia and the equine encephalomyelitis (EEM) virus 24 hours after irradiation. Irradiation prior to infection was found to decrease the survival rate. Preventive administration of Ukrain increased the survival rate.
Ukrain decreases bone-marrow suppression in rats exposed to gamma radiation by improving hemopoiesis and immunogenesis.
The radioprotective effects of Ukrain are far superior to all its components taken separately , both measured by survival of mice irradiated by different doses, and by the protection coefficient a. These observations suggest that the influence of Ukrain on radiation effects does not result from the antiradiation properties of its components but rather from the concerted action of the specific combination found in Ukrain.

Drug Interactions
Ukrain have a significant pain-killing effect on mice and interacts with morphine so that the effect of morphine diminishes. This raises concerns about their combined usage.
In another studyUkrain seemd to have pain killing properties only in very high dosis in mice, while
enhancing the effect of morphine in some test settings, and antagonizing the effect in other tests.
The interaction between Ukrain and Naltrexone, a nonselective opioid receptor antagonist, was studied in the 'writhing syndrome' test in mice. The results show that the antinociceptive effect of both single dose and prolonged administration of Ukrain is completely antagonized by Naltrexone.
Ukrain significantly (p<0.001) enhanced the anticonvulsive action of valproate in a mouse electroshock-induced seizure model. This was observed with UKRAIN doses of 9.5 and 19.0 mg/kg, but not at 4.75 mg/kg. No significant influence on the activity of other anti-epileptics (diazepam, carbamazepine, diphenylhydantoin, phenobarbital) was observed

Ukrain against infections?
Protective effect against bacterial infections
Ukrain increases the survival of mice exposed to letal doses of E.Coli ans Stafylococcus Aureus bacterias.
Antiviral effect on mice and embryos
Ukrain seems to have antiviral effect against the Influenza Virus, when tested on embryos and mice.

Other effects
Effect on bone density in rats
Ukrain was shown to affect bone tissue metabolism in rats. Its action could be slightly osteopenic at the highest doses administered to intact animals for a prolonged period of time. By far, the most important finding seems to be the anabolic effect of Ukrain on bone in ovariectomized rats, which is most probably related to induced increase in the production of sex hormones, predominantly estrogens. This means it is likely that Ukrain can counteract the loss of bone due tp estrogen deficiency in postmenopausal women.

Interactions with Alcohol?
Ukrain seems to inhibit the enzyme thay breaks down alcohol in rats. This means that there is reason to be careful when combining alcohol and Ukrain.
Ukrain and Thyroid Hormones in Rabbits
The influence of Ukrain on serum levels of thyroid hormones was studied in rabbits of both sexes. An increase in the thyroxine level was found at a dose of 1.5 and 3.0 mg/kg i.v. in male rabbits, whereas increased triiodothyronine was noted when Ukrain was given at all studied doses. In females the thyroxine level was not altered by Ukrain administration, whereas the triiodothyronine concentration was increased following Ukrain at 0.3, 1.5 and 3.0 mg/kg i.v. It is probable the altered thyroid hormone levels as a result of Ukrain application may contribute to the drug's potent immunomodulatory action.

Lack of toxicity in Rabbits
6 week Ukrain application to rabbits did not change their body organs and total body weight. The drug did not affect biochemical parameters of peripheral blood, except for a minor reduction in the total plasma level and increases in serum uric acid and urea indicating enhanced catabolism of proteins and minor changes in white blood cells.

Long term effects on rodents
A three month treatment with Ukrain significantly depressed the spontaneous locomotor
activity and did not affect the motor coordination of mice and rats of both
sexes. Ukrain did not affect the body weight gain as well as the mass of internal
organs; the exception was an increase in the mass of the spleen in rats.
Biochemical studies indicated that the three month treatment depressed
the whole brain dopamine concentrations and did not affect the noradrenaline
(NA) and Serotonin(5-HT) concentrations.
In another investigation, Ukrain showed no clinical signs of toxicity in hamsters and rats
and no teratogenic effect could be noted in either species. Slight embryotoxic effects were noted in
hamsters exposed to Ukrain at doses which were otherwise not embryotoxic to rats.
Ukrain was found to be non-mutagenic and non-genotoxic in a standardized genotoxicity experiment.
Ukrain did not show any tendences to induce any signs of allergic shock in a standardized animal experiment on mice.

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