Antitumor and antimetastatic effects of betulonic acid amides in mice with transplantable Lewis carcinoma

We studied the effects of four synthetic amides of betulonic acid containing amino acid fragments (d,l-α-alanine, β-alanine, and their methyl esters) on the rate of growth and metastatic dissemination of transplantable Lewis lung carcinoma in C57Bl/6 mice. The test compounds were administered intragastrically in a single dose of 500 mg/kg. 3-[-oxo-20(29)-lupen-28-oilamino]-propionic acid suppressed primary tumor growth (by 26%) and decreased the number of lung metastases (by more than 2 times). Antitumor and antimetastatic activity of triterpenoids decreased after methylation of the amino acid fragment in betulonic acid. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 7, pp. 78–81, July, 2006     

Antithrombogenic and Antiplatelet Activities of Extract from <Emphasis Type="Italic">Maackia amyrensis</Emphasis> Wood

Antithrombogenic and antiplatelet effects of a new drug, containing isoflavonoids (extract from the wood of Maackia amyrensis, a Far Eastern plant), were studied. A course (200 mg/kg intragastrically during 14 days) of Maackia amyrensis extract prevented intravascular clotting, initiated by application of 10% iron chloride solution on the vessel. The drug increased antiaggregant activity of the vascular wall and potentiated endothelium-dependent vasodilatation in ovariectomied rats. The reference drug ethinylestradiol (25 μg/kg intragastrically during 14 days) potentiated the antiaggregant effect of the endothelium, but was inferior to Maackia amyrensis extract in the capacity to induce endothelium-dependent vasodilatation in ovariectomied rats. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 2, pp. 164-167, February, 2009     

Licorice preparations improve efficiency of chemotherapy and surgical treatment of transplanted tumors

Experiments on animals with Lewis lung carcinoma and Ehrlich tumor showed that licorice (glycyrrhiza) extract and glyciram prepared from this plant improved the antitumor effect of cyclophosphamide. Glyciram reduced the toxic effect of the cytostatic on peripheral blood leukocytes. Licorice extract inhibited the growth of Ehrlich tumor and development of metastases in mice with Lewis lung carcinoma. Glyciram administered to mice after removal of Lewis lung carcinoma produced an antimetastatic effect and prevented relapses. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 213–217, February, 2008     

<Emphasis Type="Italic">In vivo</Emphasis> study of dihydroquercetin genotoxicity

Genotoxic properties of dihydroquercetin were in vivo studied by the method of chromosome aberrations counting and DNA-comet assay. Dihydroquercetin administered repeatedly (5 times, 0.15 and 1.5 mg/kg) or once in doses of 15, 150, and 2000 mg/kg induced no DNA damages in mouse bone marrow, blood, liver, and rectal cells. Single administration of this preparation in doses of 1.5 and 150 mg/kg and 5-fold administration in a dose of 1.5 mg/kg had no effect on the level of chromosome aberrations in mouse bone marrow cells. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 309–312, March, 2008     

Protective effect of complex antioxidant preparation containing vitamins and amino acids in rats with burn trauma complicated by endotoxemia

Burn trauma increased blood chemiluminescence, while lipopolysaccharide in a dose of 1 mg/kg potentiated this effect, activated LPO, and decreased plasma antioxidant activity. In erythrocytes, superoxide dismutase activity increased, while activity of peroxide-utilizing enzymes decreased. Myeloperoxidase content increased in the lungs and epidermis. The preparation of α-tocopherol, selenium aspartate, and ubiquinone abolished the effect of lipopolysaccharide, but did not modulate the increase in chemiluminescence under the influence of this agent. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 6, pp. 636–638, June, 2006     

Antimutagenic activity of afobazole in various regimens of treatment

The influence of a new 2-mercaptobenzimidazole derivative afobazole on cytogenetic effects of dioxidine and cyclophosphamide was studied by counting chromosome aberrations in bone marrow cells of C57B1/6 mice. Afobazole (1–100 mg/kg perorally) exhibited antimutagenic activity determined by its antioxidant properties. This activity depended on the dose and treatment shedule. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 539–542, November, 2000     

<Emphasis Type="Italic">In Vivo</Emphasis> Effect of Selective Macrophage Suppression on the Development of Intrahepatic Cholestasis in Mice

We studied the role of selective suppression of liver Kupffer cells (gadolinium chloride, 14 mg/kg intravenously) in the development of intrahepatic cholestasis in CBA/C57Bl/6 mice after intraperitoneal injection of α-naphthylisothiocyanate in a single dose of 200 mg/kg. Pretreatment with gadolinium chloride increased the severity of cholestasis and signs of liver damage. Gadolinium accumulation in the liver peaked after 24 h and was accompanied by a decrease in activities of cathepsin D and cathepsin B and concentration of matrix metalloprotease-2. Our results confirm the hypothesis that normal function of Kupffer cells and extracellular matrix plays an important role in cholestasis. Administration of gadolinium chloride serves as a convenient model to study the side effects, toxicity, and safety of lanthanides as nanoparticles. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 376–380, October, 2008     

Effect of atmospheric ammonia on mortality rate of rats with barbiturate intoxication

Ammonia inhalation (0.84–1.07 mg/liter, 3 h) was accompanied by a 65% increase in ammonia concentration in mixed blood of intact rats. This treatment did not cause death of intact animals, but potentiated the lethal effect of sodium thiopental and inhibited external respiration and O₂ consumption in animals. The resistance of rats to the lethal effect of barbiturate tended to decrease under conditions of experimental hyperammonemia induced by intraperitoneal injection of ammonium acetate in a nonlethal dose (6 mmol/kg). Our results indicate that potentiation of the toxic effect of barbiturates by atmospheric ammonia is related to its resorptive effects. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 634–636, June, 2007     

Dynamics of Antitumor Resistance after Cyclophosphamide Injection

Antitumor resistance decreased in mice 24 h after injection of cyclophosphamide in a dose of 100 mg/kg. This was seen from more rapid growth of Ehrlich’s ascitic carcinoma transplanted intraperitoneally 24 h after cyclophosphamide injection and 17% reduction of the lifespan of mice with tumors. Three, 7, 10, 14, and 22 days after cyclophosphamide injection, the antitumor resistance increased and the lifespan of animals with Ehrlich’s ascitic carcinoma transplanted at the corresponding periods increased by 20, 14, 42, 29, and 36%, respectively, in comparison with mice with transplanted tumor not injected with the drug. Injection of cyclophosphamide 1 day after tumor transplantation prolonged of the lifespan of animals with tumors by 76%.     

Fucoidan Extracted from Fucus Evanescens Brown Algae Corrects Immunity and Hemostasis Disorders in Experimental Endotoxemia

Fucoidan extracted from brown algae (Fucus evanescens) was used for correction of immunity and hemostasis disorders in experimental endotoxemia induced by injection of LPS. Fucoidan reduced the elevated levels of proinflammatory cytokines (TNF-α, IL-1, IL-6) and partially arrested hypercoagulation phenomena, thus improving animal resistance to LPS. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 71-74, January, 2009     

UHF-dielectrometry of the urine in prognosis of aggregation stability

The hypothermic effects of 5-HT_1A serotonin receptor agonist 8-OH-DPAT after intranasal, intraperitoneal, and subcutaneous administration were compared. In a dose of 1 mg/kg 8-OH-DPAT induced similar thermal reactions after administration by all three routes. In a dose of 0.5 mg/kg 8-OH-DPAT caused no appreciable changes in body temperature after intraperitoneal injection and decreased it after subcutaneous and intranasal administration. No genotypic differences in the effects of 5-HT_1A receptor agonist administered by different routes were detected in four inbred mouse strains. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 413-415, October, 2008     

Effects of β-carotene and aspartame on clustogenic activity of cyclophosphamide and dioxidine in mice

Antimutagenic effects of combination of aspartame (0.4 and 4 mg/kg) and β-carotene (0.15–15 mg/kg) were studied by estimation of chromosome aberrations in bone marrow cells of C57Bl/6 mice. Single and 5-day treatment with this combination decreased the clastogenic effects of dioxidine and cyclophosphamide and produced a more potent and universal antimutagenic effect than its constituents. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 570–573, November, 2000     

Activation of maternal behavior of albino rats after combined treatment with dopamine and opioid receptor antagonists in low doses

We studied the effect of D1/D2 antagonist haloperidol on maternal motivation in nursing albino rats. Haloperidol in a dose of 0.2 mg/kg significantly attenuated parental reactions and motor and exploratory activities. In a lower dose (0.1 mg/kg) the drug produced the same effect on maternal behavior (number of approaches to newborns) without reducing motor activity. The effect of low-dose haloperidol was different after naloxone treatment (0.2 mg/kg intranasally): the number of pup transfers increased significantly. The detected phenomenon indicates good prospects of combined treatment with agents modifying the cerebral dopaminergic and opioid systems as the method for correction of disorders in maternal behavior. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 8, pp. 124–127, August, 2006     

The effectiveness of cis-platinum,cyclophosphamide and melphalan in treating disseminated tumor cells in mice

Both B16 melanoma and Lewis lung carcinoma growing in C57/B1 mice spontaneously metastasize to the lungs and other organs. When the tumors are grown in the mouse tail to a specific volume and amputated, the spontaneously disseminated tumor cells can then be independently treated. The effects of a single dose of cyclophosphamide (200 mg/kg), cis-platinum (6 mg/kg) and melphalan (10 mg/kg) on the appearance of pulmonary and other metastases were measured. The cis-platinum treatment was shown to reduce the number and incidence of metastases of both tumors at various times after treatment. The antimetastatic effectiveness of cis-platinum against these two tumors was increased when 2·4 mg/kg was administered each day for five consecutive days after amputation of the primary. Cyclophosphamide, when administered at two-thirds maximum tolerated dose, had a small promoting effect on the number and incidence of pulmonary metastases of Lewis lung carcinoma, whereas, applied in the same dose, it had efficacy in the treatment of disseminated B 16 melanoma and inhibited appearance of both pulmonary and lymph-node metastases. When melphalan was administered in single- and multiple-dose regimens, the number and incidence of metastases of both tumors increased at various times after primary tumor amputation. These data suggest that melphalan can promote the growth of disseminated tumor cells in both the lungs and other sites and that some systemic chemotherapies may result in promotion instead of suppresssion of metastatic disease     

Effect of afobazole on teratogenic activity of cyclophosphamide in rats

A new anxiolytic afobazole (1–100 mg/kg perorally, Russia) dose-dependently abolished the embryotoxic and teratogenic effects of cyclophosphamide and reduced the range of induced malformations in outbred albino rats. Our results suggest that afobazole possesses antiteratogenic activity. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 414–417, April, 2008     

Mouse Lymphosarcomas Sensitive and Resistant to Cyclophosphamide Therapy: Activity of Cathepsins B, L, and D during Various Schemes of Treatment with Cyclophosphamide and SE-Glycan

We measured activities of cysteine (cathepsins B and L) and aspartyl proteinases (cathepsin D) in tumor tissue of mice with sensitive and resistant lymphosarcomas. In cyclophosphamide-resistant lymphosarcoma tissue activities of cathepsins B, L, and D were lower than in cyclophosphamide-sensitive lymphosarcoma. After treatment with cyclophosphamide in high doses enzyme activities in mice with cyclophosphamide-resistant lymphosarcoma increased more significantly than in animals with cyclophosphamide-sensitive lymphosarcoma. Sulfoethylated beta-1,3-D-glycan potentiated the effect of cyclophosphamide in mice with both forms of lymphosarcoma. This drug in the lowest dose (10 mg/kg) was most effective.     

Effect of radioprotector indralin on carboplatinum hemotoxicity

A decrease in carboplatinum hemotoxicity was detected in experiments on C57Bl mice treated with the drug in combination with indralin (urgent radioprotector). Carboplatinum in a dose of 125 mg/kg, injected intraperitoneally, caused 80–100% death; the median term of death was 6 days (3–17). Single oral dose of indralin (100 mg/kg) during the 1st min or 15 min after carboplatinum injection (125 mg/kg) increased animal survival by 40.0–46.7% by day 20 of the experiment primarily during the period of manifest hemotoxicity (days 7–17), indralin injected 1, 2, or 4 h after carboplatinum exhibited no chemoprotective effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 422–424, April, 2006     

<Emphasis Type="Italic">In vitro</Emphasis> immunomodulating activity of biosurfactant glycolipid complex from <Emphasis Type="Italic">Rhodococcus ruber</Emphasis>

The biosurfactant glycolipid complex synthesized by Rhodococcus ruber actinobacteria is not toxic and exhibits no appreciable effect on proliferative activity of peripheral blood leukocytes. In the monocyte fraction, the biosurfactant activates the production of IL-1β and TNF-α cytokines without modifying the production of IL-6. In the mononuclear fraction, the glycolipid biosurfactant exhibited no effects on the production of IL-1β, TNF-α, and IL-6. These results indicate good prospects for further studies of immunomodulating and antitumor activities of biosurfactant drug. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 9, pp. 301–305, September, 2007     

Correction of morphological shifts in experimental syringomyelia

The possibility of correcting morphological shifts in experimental syringomyelia with pyrimidine derivative hydroxymethyluracil (antioxidant with a wide spectrum of biological activities) was studied. Hydroxymethyluracil in a dose of 50 mg/kg prevented the development of morphological shifts characteristic of syringomyelia in the CNS of laboratory animals. Hydroxymethyluracil prevented the development of neurological symptoms and trophic disorders of the skin in rabbits with syringomyelia. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 587–588, May, 2007     

Effect of systemic treatment with antibodies against glutamate on the seizure response of C57Bl/6 mice after pentylenetetrazole kindling

We studied the effect of single intraperitoneal injection of antibodies against glutamate on acute generalized epileptiform activity induced by intravenous injection of pentylenetetrazole in kindled C57Bl/6 mice. We found that in animals at various stages of kindling, administration of antibodies against glutamate in a dose of 25 mg/kg 1.5 h before testing increases the threshold of clonic seizures and tonic phase of seizures with lethal outcome and latency of seizure development, i.e. produces an antiepileptic effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 611–613, June, 2007