Investigation of remaxol efficacy in complex therapy of experimental generalized tuberculosis on mice

Efficacy of remaxol in complex chemotherapy of generalized drug resistant tuberculosis was studied on mice. Mycobacterium tuberculosis 5419 SPBNIIF isolated from a patient with freshey diagnosticated pulmonary tuberculosis resistant to isoniazid (10 mcg/ml), rifampicin (40 mcg/ml), streptomycin (10 mcg/ml) and ethionamide (30 mcg/ml) was used in the experiments. The main polychemotherapy included 4 antituberculosis drugs in the highest therapeutic doses: isoniazid, amikacin, ethambutol and tavanic, the treatment course was 8 weeks. Remaxol was administered in a dose of 25 ml/kg intraperitoneally 5 times a week (14 injections). Significant activating effect of remaxol on the tension of the lung tissue local immunity was revealed by changes in the granuloma cell composition (from mainly epitheliod to mainly lymphoid) and by more frequent large lymphohistiocytic infiltrates. The use of remaxol also greatly increased the absorptive and digestive activity of the peritoneal macrophages phagocytosis, inhibited in the process of the experimental tuberculosis development.     

Antimutagenic properties of selected radioprotective drug mixtures with regard to X-ray-induced reciprocal translocations in mouse spermatogonia

The radioprotective drugs AET, serotonin, and ATP were tested for antimutagenic activity against induction by 4.0 Gy X-rays of reciprocal translocations in mouse spermatogonia. Single drugs administered in doses of 8, 24 and 360 mg/kg b.wt., respectively, had no effect on translocation yields recorded in diakinesis-metaphase I spermatocytes. Two-drug mixtures afforded insignificant protection. Three-drug mixtures, however, were found to reduce radiation damage considerably, and the extent of protection was dependent in part on the amount of ATP. The best effect was obtained with formulations of serotonin-AET-ATP at the following doses, respectively: 8 + 24 + 360 mg/kg, 16 + 24 + 336 mg/kg, and 16 + 32 + 264 mg/kg. Less effective were the serotonin-AET-ATP formulations: 16 + 32 + 120 mg/kg, and 8 + 24 + 480 mg/kg. Treatment with drugs omitting radiation exposure was observed to raise, though insignificantly, the level of spontaneous translocation frequency.     

Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD.     

Reducing the potential copper toxicity of concentrates to sheep by the use of molybdenum and sulphur supplements

A high copper (Cu) diet (45.3 μg Cu/g DM) was given to three groups of animals, ♂ or ♀ Scottish Blackface and ♂ Finnish Landrace lambs, without added molybdenum (Mo), or with 2, 4, 8 or 16 mg Mo/kg DM added in a 3 × 5 factorial experiment lasting 18–27 weeks. Sodium sulphate, providing 2 g S/kg, was added with each Mo supplement.Six of the nine lambs not given supplementary Mo + S died of Cu poisoning but those given Mo + S survived. Histological evidence of subclinical hepato-toxicity was found in Mo + S supplemented lambs but it decreased in severity as the level of added Mo increased. Plasma aspartate amino-transferase (PAAT) concentrations were elevated in unsupplemented lambs from week 9 and in lambs given 2 mg Mo/kg from week 12 but they remained normal in lambs given 4–16 mg Mo/kg DM. Successive increments in dietary Mo reduced the increase in liver Cu after 18–20 weeks from 1450 to 735, 483, 445 and 131 μg/g DM. The proportion of ingested Cu (y%) retained in the liver was related to dietary Mo (x, mg/kg DM) by the equation y = 2.6 ? 1.66 log x ± 0.21 (r = 0.98; 2 d.f.).Finnish Landrace lambs retained 50% less Cu in their livers, had lower PAAT levels and showed less histological evidence of liver damage than ♂ Scottish Blackface lambs. The latter had higher PAAT levels and a higher mortality from Cu poisoning than ♀ Scottish Blackface lambs although the two sexes retained similar proportions of ingested Cu in their livers.The results are discussed in relation to the practical use of Mo + S to prevent Cu poisoning in sheep.     

Short Term Training Attenuates Opening of the Mitochondrial Permeability Transition Pore Without Affecting Myocardial Function Following Ischemia-Reperfusion

Hepatotoxicity is one of the most serious adverse effects of antituberculosis drugs. The aim of this study was to produce a rat model of isoniazid-rifampicin (INH-RIF) induced hepatotoxicity. Materials and Methods: Wistar rats (100–150 g) were treated with different doses of INH i.e. 25, 50 and 75 mg/kg/day with a fixed dose of RIF i.e. 50 mg/kg/day intragastrically for a period of 28 days. Serum glutamate oxaloacetate aminotransferase (SGOT), glutamate pyruvate aminotransferase (SGPT), bilirubin (Bil) and alkaline phosphatase (ALP) were estimated at 0,14, 21 and 28 days in rats. Histological analysis was carried out to assess the liver. Results: Treatment of rats with INH–RIF (50 mg/kg/day each) induced hepatotoxicity as judged by elevated serum SGPT, SGOT, Bil and ALP as compared with their base line. Histological evaluation of INH–RIF induced hepatotoxicity also showed liver damage. Conclusion: The present study suggests that 50 mg/kg/day each of INH–RIF was selected as hepatotoxic dose (i.e. minimum dose with maximum hepatotoxicity) in wistar rats.     

Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

The use of cyclosporine A (CsA) as an immunosuppressive agent is often limited owing to its hepatotoxic and nephrotoxic properties. The present study was designed to evaluate the protective effect of metformin and silymarin in a rat model of CsA induced hepatorenal toxicity. The study included seven groups of Wistar albino rats (n = 6 per group): normal control, experimental control (CsA alone, 25 mg/kg), CsA + metformin (50 and 500 mg/kg), CsA + silymarin (50 and 200 mg/kg) and CsA + vitamin E (100 mg/kg). All the drugs were given daily for a period of 21 days by oral gavage and their effect was evaluated on serum levels of organ function markers (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, bilirubin, urea/blood urea nitrogen, creatinine), markers of oxidative stress (thiobarbituric acid reactive substances, glutathione, superoxide dismutase), inflammation (nitrite, myeloperoxidase, tumour necrosis factor‐alpha, prostaglandin E₂), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling positivity) in addition to tissue histology, cyclooxygenase (COX)‐2 and inducible nitric oxide synthase (iNOS) immunoreactivity. Administration of metformin and silymarin along with CsA ameliorated functional damage to liver and kidneys in a dose‐dependent manner. Significant and comparable improvement in the tissue levels of oxidative stress, inflammation, apoptotic markers was also observed following treatment with both the test drugs. Normalization of histology scores, as well as COX‐2 and iNOS immunoreactivity scores, further strengthened these findings. The hepatoprotective and nephroprotective effects of metformin and silymarin were comparable and matched with that of reference drug, vitamin E. The findings of the present study suggest that both metformin and silymarin have a potential for clinical use in patients receiving long‐term CsA treatment to maintain their liver and kidney functions.     

Zinc availability from zinc lipoate and zinc sulfate in growing rats

The purpose of this study was to investigate the effect of zinc lipoate and zinc sulfate on zinc availability in growing rats. 6 . 6 male albino rats were fed purified diets based on corn starch, egg albumen, sucrose, soy bean oil and cellulose over a 4-week period (diet Ia: 10 mg Zn/kg as zinc sulfate, diet Ib: 10 mg Zn/kg as zinc lipoate, diet IIa: 10 mg Zn/kg as zinc sulfate +0.4% phytic acid, diet IIb: 10 mg Zn/kg as zinc lipoate +0.4% phytic acid, diet IIIa: 20 mg Zn/kg as zinc sulfate + 0.4% phytic acid, diet IIIb: 20 mg Zn/kg as zinc lipoate + 0.4% phytic acid). Zinc lipoate and zinc sulfate both proved to be highly available zinc sources. When 0.4% phytic acid were present in the diets, apparent zinc absorption was generally depressed but was higher from zinc lipoate in tendency than from zinc sulfate. Comparable results were evident for femur zinc, plasma zinc and metallothionein concentrations in liver tissues. This indicates that zinc lipoate could be a valuable zinc source under conditions of low zinc availability. Nevertheless the absence or presence of phytic acid was a more important factor influencing zinc availability than the type of zinc source investigated.     

Liver cytochrome P-450 induction in rats by drug preparations and the body vitamin A allowance

The content of P-450 cytochrome and vitamin A was determined in the liver of mature male rats who received for a month daily parenteral administrations of phenobarbital solutions (Pb; 40 mg/kg), rheopyrine (a mixture of equal aliquots of amidopyrine and butadione; 200 mg/kg), amidopyrine (100 mg/kg) or water (control). The animals were kept on a semisynthetic diet, receiving once, every week 400 IU of retinol-palmitate per rat. Pb administration markedly (more than threefold) increased P-450 cytochrome content in the liver. Rheopyrine and amidopyrine also elevated its level, but to a lesser extent than Pb. Pb and rheopyrine also depressed vitamin A levels in the liver and caused either a trend towards its decrease (Pb) or a significant decrease (rheopyrine) of its overall content in the liver. The effect of amidopyrine on the concentration and storage of retinol in the liver was less pronounced. The data obtained suggest that the drugs inducing P-450 cytochrome are capable of disturbing vitamin A content in the body.     

Experimental effect of lysozyme on macrophage metabolism and resistance to infection

The peritoneal macrophages of mice treated with lysozyme were studied by cytochemical assay. In single and repeated doses of 0.5-5 mg/kg lysozyme induced an increase in macrophage metabolism. This was evident from an increased activity of succinate dehydrogenase, NADP X N-DH and the enzymes catalyzing glycolysis typical of these cells (lactate dehydrogenase and alpha-glycerophosphate). The changes in the activity of the enzymatic systems were most pronounced in minute and less mature macrophages after repeated administrations of the drugs. In a dose of 50 mg/kg lysozyme somewhat decreased the activity of a number of the enzymes. In the doses optimal for the macrophage activity lysozyme had a low effect on the infection resistance and slightly increased the cephotaxim efficiency in experimental staphylococcal infection. This may be mainly due to the immunomodulating effect of lysozyme and its low effect on the large macrophages having the bactericidal effect.     

不同剂量炔雌醚对小鼠器官鲜重、繁殖生理和肝肠CYP3A4酶含量的影响

为探究不同剂量炔雌醚对小鼠器官、激素和肝肠药解酶的影响,分别以0.008 mg/kg、0.04 mg/kg、0.2 mg/kg、1.0 mg/kg和5.0 mg/kg的炔雌醚油溶液连续3d灌胃小鼠,首次给药7d后解剖取材,检测其器官鲜重、雄鼠精子数量、血清中激素浓度、小肠和肝脏中CYP3 A4酶含量的变化.结果 发现:...     

Assessment of the protective and therapeutic effect of melatonin against thioacetamide‐induced acute liver damage

Acute or chronic damage to the liver may occur through alcohol, drugs, viruses, genetic disorders, and toxicity. In this study, we planned to investigate the protective and therapeutic effects of melatonin (Mel) by causing damage to the liver with thioacetamide (TAA). Thirty‐five rats were used. Group I: control group (seven pieces), group II: Mel group (seven pieces) the single dose on the first day of the experiment was 10 mg/kg, group III: TAA (seven pieces) 300 mg/kg with 24‐hour intervals, two doses, group IV: Mel + TAA group (seven pieces) 10 mg/kg single dose Mel was applied 24 hours before TAA application, group V: TAA + Mel group (seven pieces) single dose (24th hour) of 10 mg/kg Mel was administered after TAA (300 mg/kg) two doses. The liver histology was evaluated. Apoptosis, autophagy, and necrosis markers in tissue were determined by immunohistochemistry. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in blood serum samples and transforming growth factor‐β (TGF‐β) and tumor necrosis factor‐α (TNF‐α) levels were determined in liver tissue. TAA affected histologically the classical lobule structure both in cell cords and sinusoids. Caspase‐3, RIP3, and LC3 levels were increased in group III compared with the control group. TAA did not cause a statistically significant change in TNF‐α level but decreased the TGF‐β level significantly. AST and ALT levels were statistically significant in group II and V compared with group I, the ALP level was significant in group IV compared with group II. The results of this study showed that TAA caused significant damage to tissues and increased cell death, Mel was found to have more therapeutic than the protective effect on tissues.     

Experimental chemotherapy of schistosomiasis mansoni. XIII. Activity of praziquantel, an isoquinoline-pyrazino derivative, on mice, hamsters and Cebus monkeys.

In mice experimentally infected with Schistosoma mansoni, praziquantel (2-cyclohexylcarbonyl-1,3,4,6,7,11b-hexahydro-2H-pyrazino[2,1-a]isoquinoline-4-one), administered orally at the levels of 100 and 50 mg/kg, for 5 consecutive days, produces oogram changes in all animals and a pronounced hepatic shift of schistosomes (97.1 and 89.1, respectively). At lowest levels (12.5 and 6.3 mg/kg), alterations in the oogram could still be detected, although hepatic shift of schistosomes was no more evident. After a single intramuscular injection, the results obtained paralleled those observed with a single-dose oral treatment. The hepatic shift was only moderate at 200 and 100 mg/kg and the percentages of worms retained in the liver, after perfusion, were particularly low. When nasal route in a 1-day regimen was used, the results obtained were slightly less evident as compared with those observed by oral route (5-day schedule). Considering the percentage of oogram changes, the degree of hepatic shift of schistosomes and the percentage of worms fixed in the liver, the antischistosomal activity of praziquantel was greater in hamsters than in mice. Actually, a daily dose as low as 12.5 mg/kg, administered for 5 consecutive days, was sufficient to shift 60.4% of the worms towards the liver and to produce alterations of the oogram in 60% of the animals. In Cebus monkeys orally treated with 10 and 20 mg/kg of praziquantel, given 3 times within a single day (total doses of 30 and 60 mg/kg, respectively), a remarkable reduction in worm burden was observed. A single oral or intramuscular dose of 100 mg/kg was found to be curative. One Cebus doses with 100 mg/kg, by nasal spray, was found to harbor only female worms at autopsy performed 69 days after treatment.     

Antiulcerous efficacy of reamberin at the background of the stress ulcerogenic factor action

The effect of reamberin on morphofunctional changes in the small intestine mucous membrane due to stress ulcerogenesis was studied. Normalization of the lipid modifications in the tissue structure, evident of the drug antiulcerous properties, was observed.     

Experimental study of a gentamicin aerosol]

The study of gentamicin aerosol showed its relative innocuousness: it did not inhibit the growth and development of young animals, did not induce pathological changes in the upper respiratory tract, kidneys, liver, heart and spleen on its prolonged use. Pathohistological examination revealed slight irritating effect of the gentamicin aerosol in the lungs after its use in a dose of 8 or 25 mg/kg for 6 weeks. A procedure for investigating the effect of the aerosol on the activity of the trachea ciliated epithelium of warm blooded animals was developed. The gentamicin aerosols prepared from solutions of different concentrations (1 to 50 mg/ml) induced ingibition of the ciliated epithelium function at average from 15 to 35 per cent which was associated with the solution acidity (pH 4.54 to 4.82). Such a decrease in the function of the ciliated epithelium due to the antibiotic aerosol use was a factor prolonging the antibiotic retention time in the respiratory organs. It was found that aqueous solutions of drugs used for inhalation, such as ephedrin, euphelin, dimedrol, N-acetyl-L-cystein and others had no effect on the activity of gentamicin and may be used with it in a form of aerosols.     

Influence of protective drugs on the elevation of extracellular potassium ion concentration in the brain during ischaemia

Influence of drugs on the changes of extracellular potassium ion concentration in the brain during total cerebral ischaemia was investigated. The aorta of the dogs was clamped twice with an intermittent reperfusion period of 60 min. In control experiments no significant difference was found in the elevation of extracellular potassium ion concentration of the brain during the first and second clampings. In the present study drugs were administered 10 min prior the second aorta occlusion. Verapamil in a dose of 0.125 mg/kg proved to be ineffective. Piridoxilate in a dose of 10 mg/kg and piracetam in a dose of 100 mg/kg delayed to a small extent the potassium outflow. The following drugs enhanced significantly the duration before the steep increase of potassium ion outflow: phenytoin in a dose of 10 mg/kg by 31.8 sec (p less than 0.01), ethyl-butyl-thiobarbital in a dose of 15 mg/kg by 30.2 sec (p less than 0.05), and lidocaine in a dose of 100 mg/kg by 115.8 sec (p less than 0.01). Comparing present results to our earlier data (obtained after 50 sec ischaemia) it can be concluded, that these protective influences become more effective during longer ischaemic period (2-5 min), when lidocaine, phenytoin and ethyl-butyl-thiobarbital were used. Moreover, in spite of the observation seen during shorter ischaemia, even piridoxilate and piracetam exerted some degree of protective effect. No such effect of verapamil could be detected in the present experimental model.     

Pharmacodynamics of mefloquine and praziquantel combination therapy in mice harbouring juvenile and adult Schistosoma mansoni

Praziquantel (PZQ) is currently the only drug widely used for the treatment of schistosomiasis, but the antimalarial drug mefloquine (Mef) possesses interesting antischistosomal properties. Combination therapy with these two drugs has been suggested as a strategy for transmission control, as PZQ is active against adult worms and Mef is active against schistosomula. To examine the efficacy of combination therapy, Schistosoma mansoni-reinfected mice were separated into seven groups: untreated (I), treated with PZQ in doses of 200 mg/kg (II) or 1,000 mg/kg (III), treated with Mef in doses of 200 mg/kg (IV) or 400 mg/kg (V); each dose was divided equally and given on two consecutive days. Group VI was treated with doses of PZQ + Mef as in groups II and IV, respectively, while group VII was treated with PZQ + Mef as in groups III and V, respectively. PZQ + Mef at the reduced doses of 200 mg/kg each enhanced the therapeutic efficacy over the reduced PZQ dose alone as shown by a very high reduction in the total numbers of mature worms (95% vs. 49%), immature worms (96% vs. 29%) and the complete eradication of immature females, mature females and immature eggs. The reduction in worm burden was associated with the healing of hepatic granulomatous lesions and the normalisation of all liver enzymes. Therefore, the use of Mef with PZQ is more effective than PZQ alone and should be considered for clinical trials in humans as a potential treatment regimen to prevent treatment failures in areas with high rates of schistosomiasis.     

Radioprotection by mangiferin in DBAxC57BL mice: a preliminary study

The radioprotective effects of various concentrations (0, 0.25, 0.5, 1, 2, 5, 10, 17.5, 25, 50, 75 and 100 mg/kg b.wt.) of mangiferin (MGN) was studied in the DBAxC57BL mice whole body exposed to 10 Gy of gamma-irradiation. Treatment of mice with different doses of MGN, one hour before irradiation reduced the symptoms of radiation sickness and delayed the onset of mortality when compared with the non-drug treated irradiated controls. The radioprotective action of MGN increased in a dose dependent manner up to 2mg/kg and declined thereafter. The highest radioprotective effect was observed at 2mg/kg MGN, where greatest number of animals survived against the radiation-induced mortality. The administration of 0.5, 1, 2, 5, 10 and 17.5 mg/kg MGN reduced the radiation-induced gastrointestinal death as evident by a greater number of survivors up to 10 days in this group when compared with the DDW + 10 Gy irradiation group. A similar effect of MGN was observed for the radiation-induced bone marrow deaths also. Our study demonstrates that mangiferin, a gluosylxanthone, present in the Mangifera indica protected mice against the radiation-induced sickness and mortality and the optimum protective dose of 2mg/kg was 1/200 of LD50 dose (400 mg/kg) of MGN. The administration of 400 mg/kg MGN induced 50% mortality, therefore LD50 of the drug was considered to be 400 mg/kg.     

Effect of selenium status on mRNA levels for glutathione peroxidase in rat liver

To determine the effect of Se status on the level of mRNA for Se-dependent glutathione peroxidase (EC 1.11.1.9), rats were fed either a Se-deficient torula yeast diet (less than 0.02 mg Se/kg diet) or a Se-adequate diet (+0.2 mg Se/kg as Na2SeO3) for greater than 135 d. Liver glutathione peroxidase activity was 0.025 for Se-deficient versus 0.615 EU/mg protein for Se-adequate rats. Total liver RNA and polyadenylated RNA were isolated and subjected to Northern blot analysis using a 700 bp DNA probe from cloned murine glutathione peroxidase. Autoradiography showed that Se-deficient liver had 7-17% of the mRNA for glutathione peroxidase present in Se-adequate liver, suggesting that Se status may regulate the level of mRNA for this selenoenzyme.     

Renin-angiotensin system inhibitors combined with cisplatin exacerbate cisplatin-induced nephrotoxicity in mice

IntroductionWe previously reported that the concomitant use of enalapril and telmisartan exacerbates the risk of cisplatin (CDDP)-induced acute renal dysfunction compared to other antihypertensive drugs in mice. Thus, in the current study, we investigated the risk of developing chronic kidney disease following repeated concomitant use of CDDP and antihypertensive drugs.Materials and MethodsMale BALB/c mice were divided into 12 groups: (1) Control group (untreated), (2) CDDP group (7 mg/kg, CDDP), (3) AML group (5 mg/kg, amlodipine), (4) ENA group (2.5 mg/kg, enalapril), (5) TEL group (10 mg/kg, telmisartan), (6) LOS group (10 mg/kg, losartan), (7) CDDP+AML group (5 mg/mL, AML), (8) CDDP+ENA group (2.5 mg/kg, ENA), (9) CDDP+LowENA group (1.25 mg/kg, ENA), (10) CDDP+TEL group (10 mg/kg, TEL), (11) CDDP+LowTEL group (5 mg/kg, TEL), and (12) CDDP+LOS group (10 mg/kg, LOS). CDDP was administered intraperitoneally four times every 7 days, and each antihypertensive drug was administered orally from day 3 before CDDP administration until day 24 (six times a week). The degree of renal damage was assessed. The nephrotoxicity of each individual was evaluated by measuring serum creatinine and blood urea nitrogen levels. The degrees of renal fibrosis and epithelial-mesenchymal transition were also examined in kidney tissue sections.Results and DiscussionThe results suggest that combinatorial treatment of CDDP and renin-angiotensin system inhibitors, particularly ENA and TEL, may exacerbate CDDP-induced nephrotoxicity. This study clearly demonstrates the need for large-scale clinical studies to construct treatment regimens that do not interfere with the therapeutic intensity of CDDP.     

Effect of apressin, obsidan, diprazine and their combination on the concentration of NAD and NADH2 in the liver and brain of hypoxic rats]

Apressin (2.5 mg/kg), obsidan (10 mg/kg), and diprazine (10mg/kg) caused an increase in the content of NAD + NAD.H2, without affecting their ratio, in the liver and brain of intact animals. These drugs, taken in the same doses, especially when used together, caused an increase in the NAD + NAD.H2 level; as to NAD/NAD.H2 ratio--it decreased in the state of hypoxia. The authors believe the antihypoxic action of apressin, obsidan, and diprazine to be connected with the rise in the total nicotinamide adenine denucleotide content and with increase of its oxidized form.