Life Span Of Experimental Animals Research Articles

Mechanisms underlying retardation of aging by dietary energy restriction.

Moderate restriction of dietary energy intake, referred to here as dietary restriction (DR), delays aging and extends lifespan in experimental animals compared with a diet of ad libitum feeding (AL) control animals. Basic knowledge of the mechanisms underlying the effects of DR could be applicable to extending the healthspan in humans. This review highlights the importance of forkhead box O (FoxO) transcription factors downstream of the growth hormone-insulin-like growth factor 1 signaling in the effects of DR. Our lifespan studies in mice with heterozygous Foxo1 or Foxo3 gene knockout indicated differential roles of FoxO1 and FoxO3 in the tumor-inhibiting and life-extending effects of DR. Subsequent studies suggested a critical role of FoxO3 in metabolic and mitochondrial bioenergetic adaptation to DR. Our studies also verified hypothalamic neuropeptide Y (Npy) as a vital neuropeptide showing pleiotropic and sexually dimorphic effects for extending the healthspan in the context of nutritional availability. Npy was necessary for DR to exert its effects in male and female mice; meanwhile, under AL conditions, the loss of Npy prevented obesity and insulin resistance only in female mice. Overnutrition disrupts FoxO- and Npy-associated metabolic and mitochondrial bioenergetic adaptive processes, causing the acceleration of aging and related diseases.

Pharmacological action and physiological effect of the venom of the honey bee Apis mellifera Caucasica

The present’s experimental data on the influence of the venom of the honey bee on the life span of experimental animals irradiated with small doses of gamma radiation on physiological and pharmacological action venom of the honey bee Apis mellifera Caucasica. The aim of the studies was to study the radioprotective effect of the pre-introduced venom Apis mellifera Caucasica with a single gamma irradiation of 60Co mice at doses of 1.3, 5, 7, 10 Gy at irradiation dose rates of 1 Gr / min. Injection of venom followed by gamma irradiation of 60Co at a dose of D = 1, 3, 5 and 7 Gy at an irradiation dose rate of 1 Gy / min increased the life span of the experimental groups of mice ranging from 45% to 56 % and from 52% to 67%, respectively. An increase in the lifespan of experimental rats exposed to radiation with the preliminary introduction of the venom of the honey bee.

20S Proteasome Intratumoral Delivery Effect on Lifespan of Melanoma-bearing Mice

The ubiquitin-proteasome system is involved in the regulation of most major intracellular processes, and disruptions in the functioning of this system lead to various pathologies. The proteolytic core of this system, 20S proteasome, was found in the physiological fluids of both healthy people and patients suffering from various inflammatory, autoimmune and oncological diseases. It has been observed that the concentration of extracellular proteasomes correlates with the severity of the disease, however, the function of proteasomes in extracellular space is still unknown. To understand the function of proteasomes in extracellular space, we evaluated the effect of intratumoral administration of the exogenous pool of 20S proteasomes purified from cells on a mouse model of melanoma. We showed that intratumoral administration of 20S proteasomes led to a small (slightly less than 20%) increase in the lifespan of experimental animals.

Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model

Aim. To study antitumor and anti - metastatic action of AKh-554, 2-Aminium-7-(Diethylamino)-4-(4-Metoxibenzo[d][1,3]dioxol-5-yl)-4H-chromene-3-carbonytril N-Acetylamino - ethanoate, on in vivo model of lung adenocarcinoma patient - derived xenograft model. Materials and methods. In 40 immunodeficient nu/nu BALB/c female mice with heterotopic patient - derived lung adenocarcinoma xenograft model antitumor and anti - metastatic effects of 2-aminochromene derivative, AKh-554 at dose 50 mg/kg intragastrically during 7 days, were explored. Laboratory animals were randomly designated into four groups - intact mice, control, referent drug and main group. We used Cyclophosphamide as referent drug. In the tumor tissue of the animals treated with the derivative through intragastric rout we quantitively detected TUBB3, ALK and c-MET/HFG levels.Results. AKh-554 more than 7.5 times decreases both the growth rate and size of xenograft tumor when compared with control group ( p =0.001), and possesses an anti - metastatic effect. Experimental treatment up to 103±2 days increases the lifespan of tumor carriers ( p =0.001 when compared with the control; p =0.03 when compared with cyclophosphamide), and induces remission in 60% of all cases. The established effect is due to activation of tumor cells apoptosis associated with decrease in tumor tissue ALK concentration (2.77±0.54 ng/ml; p =0.001 when compared with the control and cyclophosphamide). Experimental models demonstrate no signs of pharmacological resistance to AX-554, which is confirmed by the absence of differences of c-MET/HFG tissue level in all the studied groups (0.16±0.07 ng/ml - control; 0.09±0.03 ng/ml - Cyclophosphamide; 0.10±0.04 ng/ml - AKh-554).Conclusions. AKh-554 more effectively than Cyclophosphamide inhibits xenograft tumor growth and its metastatic activity. The compound increases more than 3.3 times when compared with the control the lifespan of experimental animals and induces remission of the malignant process in 60% of tumor carriers. The compound anticancer property is due to anti-ALK-mediated activation of tumor cells’ apoptosis and suppression of cell proliferation processes.

Cytotoxic and Antitumor Activity of Liposomal Silibinin

The cytotoxic and antitumor effect of liposomal form of silibinin was studied. It was shown that the liposomal silibinin reveals more pronounced cytotoxic activity in vitro against HeLa (cervix carcinoma), HT1080 (fibrosarcoma), and MCF-7 (breast adenocarcinoma) human tumor cell lines compared with non-liposomal silibinin. In vivo experiments demonstrated a possibility of parenteral use of the liposomal form. It was demonstrated that intravenous administration of liposomal silibinin has a significant antitumor effect in vivo against murine adenocarcinoma of Ca 755 and leads to inhibition of tumor growth (53.6%) and an increase (49.4%) in the mean life span of experimental animals compared to untreated control and animals receiving non-liposomal forms (free silibinin and its mixture with lecithin) administered orally.

Interpretation of data about the impact of biologically active compounds on viability of cultured cells of various origin from a gerontological point of view

Problems related to the interpretation of data obtained during testing of potential geroprotectors in cytogerontological experiments are considered. It is emphasized that such compounds/physical factors should influence the processes leading to the age-related increase of death probability of multicellular organisms (primarily human, in whose aging gerontologists are mainly interested). However, in the authors’ opinion, compounds that can be used to treat age-related diseases can hardly be classified as geroprotectors. It is noted that, in the model systems using cultured cells, researchers usually evaluate their viability, the criteria of which strongly depend on the aging theory that is shared by the experimenters. In addition, it is very important what cells are used in the studies—normal or transformed cells of multicellular organisms, unicellular eukaryotic or prokaryotic organisms, etc. In particular, the biologically active compounds that decrease the viability of cultured cancer cells, similarly to the compounds that increase the viability of normal cultured cells, may increase the life span of experimental animals and humans. Various problems with interpretation of data obtained with the Hayflick model, the stationary phase aging model, and the cell kinetics model, as well as in experiments on evaluation of cell colony-forming efficiency, are analyzed. The approaches discussed are illustrated on the example of the results of gerontological studies of rapamycin, a well-known mTOR inhibitor. It is assumed that factors retarding the stationary phase aging (chronological aging) of cultured cells are, apparently, the most promising geroprotectors, although the specific mechanisms of their action may vary considerably.

Light pollution, desynchronosis, and aging: State of the problem and solutions

The effect of different light conditions (constant illumination, light deprivation, the standard regime of lighting and natural lighting of Northwest Russia in different seasons of the annual cycle) on indicators of biological age and homeostasis, the development of age-related pathology, oncogenesis, and the lifespan of rats was investigated. The effect of exposure to constant light on the studied parameters was evaluated at different ages (antenatal, early and late postnatal periods). The data on influences of preparations and hormones of the pineal gland on biomarkers of aging, homeostasis, spontaneous oncogenesis, and lifespan in experimental animals were obtained. It was revealed that light pollution and disturbance of the photoperiod lead to desynchronosis and, as a result, to premature aging of the organism and age-associated diseases. Ways of prevention of accelerated aging were outlined.

Rapamycin prevents strong phosphorylation of p53 on serine 46 and attenuates activation of the p53 pathway in A549 lung cancer cells exposed to actinomycin D

The activation of the p53 pathway by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a molecule that mimics metabolic stress, is attenuated by rapamycin, an inhibitor of mTOR kinase, immunosuppressant, and cancer drug. Rapamycin also extends lifespan in experimental animals. Because AICAR is a relatively weak activator of p53, we investigated whether stimulation of p53 by the strong activator actinomycin D is also sensitive to the inhibitory effect of rapamycin. In A549 lung cancer cells, activation of p53 by actinomycin D was associated with phosphorylation of p53 on Ser46. Rapamycin inhibited the accumulation of phospho-Ser46 p53, attenuated upregulation of some p53 target genes, and altered cell-cycle progression. Moreover, in cells exposed to actinomycin D, rapamycin attenuated the accumulation of PML, a protein that in some conditions stimulates Ser46 phosphorylation. However, Ser46 phosphorylation was not diminished in PML-knockdown cells, suggesting that in our system PML does not play a major role in stimulating p53 phosphorylation on Ser46. Knockdown of p53 diminished the upregulation of PML by stress-inducing agents, consistent with the idea that PML is a p53-regulated gene. Our data suggest that the attenuation of p53 phosphorylation on Ser46 may play a significant role in the biological activity of anti-aging rapamycin.

The effect of low and high plasma levels of insulin-like growth factor-1 (IGF-1) on the morphology of major organs: studies of Laron dwarf and bovine growth hormone transgenic (bGHTg) mice.

It is well known that somatotrophic/insulin signaling affects lifespan in experimental animals. To study the effects of insulin-like growth factor-1 (IGF-1) plasma level on the morphology of major organs, we analyzed lung, heart, liver, kidney, bone marrow, and spleen isolated from 2-year-old growth hormone receptor knockout (GHR-KO) Laron dwarf mice (with low circulating plasma levels of IGF-1) and 6-month-old bovine growth hormone transgenic (bGHTg) mice (with high circulating plasma levels of IGF-1). The ages of the two mutant strains employed in our studies were selected based on their overall ~50% survival (Laron dwarf mice live up to ~4 years and bGHTg mice up to ~1 year). Morphological analysis of the organs of long-living 2-year-old Laron dwarf mice revealed a lower biological age for their organs compared with normal littermates, with more brown adipose tissue (BAT) surrounding the main body organs, lower levels of steatosis in liver, and a lower incidence of leukocyte infiltration in different organs. By contrast, the organs of 6-month-old, short-living bGHTg mice displayed several abnormalities in liver and kidney and a reduced content of BAT around vital organs.

Reciprocal cross differences in Drosophila melanogaster longevity: an evidence for non-genomic effects in heterosis phenomenon?

Reciprocal cross effects (i.e., differences between reciprocal hybrids that are developed by reversing the strains from which the dam and the sire are taken) are commonly used as a measure of sex-linkage or maternal effects. However, the papers reporting parental effects on life span of experimental animals are scarce. In order to investigate the potential of parent-of-origin effects for the longevity of hybrids, we determined the life spans of the inbred lines of Drosophila melanogaster [Oregon-R (OR), Canton-S (CS) and Uman (Um)] that differ significantly in longevity, as well as the life span of the progeny from the reciprocal crosses among them. The hybridization caused the increase in both flies' mean and maximum life span mainly shifting the survival curves upward proportionally at all ages. This resulted in the reduction in the Gompertz intercept (frailty) whereas the Gompertz slope (the rate of aging) was predominantly unchanged. Better-parent heterosis was observed in hybrids between OR and Um inbred lines and the extent of heterosis was more pronounced in hybrids between CS and Um inbred lines if long-lived parent was used as the female parent, and short-lived parent was used as the male parent in the crossing scheme. Such discrepancy in life span between reciprocal crosses may indicate that non-chromosomal factors are significantly contributing to a heterotic response. Our data are in line with the previous reports suggesting the involvement of non-genomic factors, particularly epigenetic events attributed to hybridization, in the manifestation of heterosis.

Effect of Amtizol on Resistance of SHR Mice to Acute Hypoxia with Hypercapnia under Conditions of Isolated Functioning of One Cerebral Hemisphere

Antihypoxant amtizol (25 mg/kg) prolonged the lifespan of intact SHR mice by 46.2% under conditions of isolated functioning of one cerebral hemisphere. The effect of amtizol on sham-operated animals was less pronounced: the lifespan of mice was prolonged by just 28.1%. Injection of amtizol to mice with active right hemisphere significantly prolonged the lifespan of experimental animals (by 64.8%). The drug was ineffective under conditions of active left hemisphere: the result coincided with the lifespan of similar mice without the drug injection. Hence, antihypoxic effect of amtizol was largely determined by its effect on the right, but not the left cerebral hemisphere.

Prolonged Strenuous Exercise Expands the Population of Developmentally Early Stem Cells in Bone Marrow (BM) and Mobilizes Them Into Peripheral Blood - Novel Evidence That Strongly Supports a Positive Effect of Physical Activity On Extension of Life Span At the Level of Stem Cells

Abstract 584 Background.Bone marrow (BM) contains a variety of stem cells, including hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), and the developmentally most primitive very small embryonic-like stem cells (VSELs). Evidence has accumulated that HSPCs (Circ J. 2008;72:897) and EPCs (J Am Coll Cardiol. 2004;43:2314) are mobilized into PB during strenuous exercise. Therefore, we became interested in whether a pool of bone marrow (BM)-residing developmentally more primitive, highly quiescent, early stem cells (VSELs) would respond to stimuli related to prolonged, strenuous exercise. As we have demonstrated previously, these cells play an important role in tissue/organ rejuvenation and their number positively correlates with life span in experimental animals (Age 2012 in press doi:10.1007/s11357-011-9364-8). Hypothesis.We hypothesized that the positive effect of physical activity may be explained by the expansion of a developmentally early pool of highly quiescent stem cells that play a role in tissue/organ rejuvenation. Experimental strategies.To test the effect of exercise on the BM pool of stem cells, we employed C57Bl6 mice that were exposed to short (1 day), mid-term (14 days), and long- term (6 months) strenuous exercise in rotating wheels. These mice were subsequently sacrificed 1h after removal from the rotating wheels, and we i) measured changes in peripheral blood cell counts, ii) enumerated the number of VSELs and HSPCs both in BM and PB of sacrificed animals by FACS analysis, iii) performed clonogeneic in vitro methylocellulose assays to enumerate the number of CFU-GM and BFU-E mobilized into PB and the number of these cells residing in the BM microenvironment, iv) employed the in vivo bromodeoxyuridine (BrdU) incorporation assay to evaluate the number of VSELs and HSPCs in BM undergoing cell division, and finally v) performed a molecular analysis of the expansion and mobilization of VSELS by measuring the expression of genes regulating stem cell pluripotency at the mRNA (RQ-PCR) and protein levels (immunofluorescence of cells fixed on cytospin slides). Results.Our data confirmed that strenuous exercise mobilizes Sca-1+Lin–CD45+ HSPCs into PB, and, for the first time, we show that prolonged, enforced exercise of mice in rotating wheels is associated with expansion in BM and mobilization into PB of the most primitive population of stem cells, Sca-1+Lin–CD45– VSELs. The expansion of VSELs in BM and their mobilization into PB was confirmed by FACS analysis, immunohistochemical staining, and RQ-PCR analysis for expression of genes that regulate pluripotency (e.g., Oct-4 and Nanog) in small Sca-1+Lin–CD45–cells sorted from BM and PB. The proliferation of VSELs, which are a quiescent population of BM-residing stem cells, has been confirmed by BrdU incorporation. In contrast to VSEL expansion, we did not observe significant changes in the number of BM-residing HSPCs. As expected, mice exposed to prolonged exercise exhibited a significant increase in skeletal muscle and a decrease in abdominal fat. Conclusions.BM-residing stem cells respond to prolonged strenuous exercise by expansion and subsequent mobilization into PB of BM-residing VSELs, which, as proposed by us and others, may play an important role in tissue/organ rejuvenation and thus positively affect life span. Therefore, our data for the first time demonstrates a positive correlation between exercise and the expansion of a most primitive pool of stem cells in BM.This work is supported by the EU Innovative Economy Operational Program POIG.01.01.02-00-109/09-01 Disclosures:Ratajczak:Neostem Inc: Member of SAB Other.

Morphology of ovaries in laron dwarf mice, with low circulating plasma levels of insulin-like growth factor-1 (IGF-1), and in bovine GH-transgenic mice, with high circulating plasma levels of IGF-1.

BackgroundIt is well known that somatotrophic/insulin signaling affects lifespan in experimental animals, and one of the signs of aging is progressive gonadal dysfunction.MethodsTo study the effects of insulin-like growth factor-1 (IGF-1) plasma level on ovaries, we analyzed ovaries isolated from 2-year-old growth hormone receptor knockout (GHR-KO) Laron dwarf mice, with low circulating plasma levels of IGF-1, and 6-month-old bovine growth hormone transgenic (bGHTg) mice, with high circulating plasma levels of IGF-1. The ages of the Laron dwarf mutants employed in our studies were selected based on their overall survival (up to ~ 4 years for Laron dwarf mice and ~ 1 year for bGHTg mice).ResultsMorphological analysis of the ovaries of mice that reached ~50% of their maximal life span revealed a lower biological age for the ovaries isolated from 2-year-old Laron dwarf mice than their normal-lifespan wild type littermates. By contrast, the ovarian morphology of increased in size 6 month old bGHTg mice was generally normal.ConclusionOvaries isolated from 2-year-old Laron dwarf mice exhibit a lower biological age compared with ovaries from normal WT littermates at the same age. At the same time, no morphological features of accelerated aging were found in 0.5-year-old bGHTg mice compared with ovaries from normal the same age-matched WT littermates.

Creatinyl amino acids—new hybrid compounds with neuroprotective activity

Prolonged oral creatine administration resulted in remarkable neuroprotection in experimental models of brain stroke. However, because of its polar nature creatine has poor ability to penetrate the blood-brain barrier (BBB) without specific creatine transporter (CRT). Thus, synthesis of hydrophobic derivatives capable of crossing the BBB by alternative pathway is of great importance for the treatment of acute and chronic neurological diseases including stroke, traumatic brain injury and hereditary CRT deficiency. Here we describe synthesis of new hybrid compounds-creatinyl amino acids, their neuroprotective activity in vivo and stability to degradation in different media. The title compounds were synthesized by guanidinylation of corresponding sarcosyl peptides or direct creatine attachment using isobutyl chloroformate method. Addition of lipophilic counterion (p-toluenesulfonate) ensures efficient creatine dissolution in DMF with simultaneous protection of guanidino group towards intramolecular cyclization. It excludes the application of expensive guanidinylating reagents, permits to simplify synthetic procedure and adapt it to large-scale production. The biological activity of creatinyl amino acids was tested in vivo on ischemic stroke and NaNO(2) -induced hypoxia models. One of the most effective compounds-creatinyl-glycine ethyl ester increases life span of experimental animals more than two times in hypoxia model and has neuroprotective action in brain stroke model when applied both before and after ischemia. These data evidenced that creatinyl amino acids can represent promising candidates for the development of new drugs useful in stroke treatment.

New Vistas on Oxidative Damage and Aging

Age-associated rises in oxidative damage are assumed to be a central phenomenon of aging. Their attenuation is an aim for both healthy aging and life extension. This review intends to critically discuss the potential of anti-oxidant actions, but even more to direct the attention to the modes of radical avoidance and to regulatory networks involved. Mitochondria seem to play a decisive role in radical formation and cellular decline. Avoidance and repair of disruptions in the electron transport chain reduce electron leakage and, thus, oxidative damage. Several low molecular weight compounds, such as melatonin, its metabolite N1-acetyl-5-methoxykynuramine, resveratrol, α-lipoic acid, and various mitochondrially targeted nitrones are capable of supporting mitochondrial electron flux. Some of them have been successfully used for extending the lifespan of experimental animals. Importantly, chemopreventive effects of these substances against cancer development should not be confused with a slowing of the aging process. We also focus on connections between these compounds and mitochondrial biogenesis, including the roles of sirtuins and signaling via peroxisome proliferator-activated receptor-γ coactivator-1α, the participation of the circadian oscillator system in radical avoidance, as well as the potentially beneficial or detrimental effects of NO, as either a regulator or a source of mitochondrial dysfunction. Especially in the central nervous system, anti-excitatory actions by melatonin, kynurenic acid and theanine are discussed, which seem to prevent calcium overload that results in mitochondrial dysfunction. New findings on direct binding of melatonin to the amphipathic ramp of Complex I may indicate an additional regulatory role in the avoidance of electron leakage.

Gene regulation by growth hormone

Since the somatomedin hypothesis of growth hormone (GH) action was first formulated more than 50 years ago, the key roles of both GH and insulin-like growth factor-I (IGF-I) in human growth have been extended to include important effects on tissue maintenance and repair. More recent observations have revealed that this pathway has a negative side, as it has been implicated as a potential contributor to the development of several human cancers and has been linked to diminished lifespan in experimental animals. This brief review focuses on fundamental aspects of gene regulation by GH, as long-term hormonal effects all require changes in gene expression. Topics to be discussed include GH-stimulated signal transduction pathways, mechanisms of gene activation and gene repression by GH, and an analysis of control of IGF-I gene transcription by the GH-stimulated transcription factor, signal transducer and activator of transcription (Stat)5b.

Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys

Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.

Experimental vasoprotection by a novel erythrocyte-derived depressing factor in rats with arterial calcinosis

Erythrocyte-derived depressing factor (EDDF) shows significant protective effects on blood vessels from hypertensive rats, by regulating vascular reactivity, calcium homeostasis, DNA synthesis, and cell cycle progression in vascular smooth muscles (VSMCs). Arteries from hypertensive and aging people have high levels of accumulated calcium. However, in the life span of experimental animals commonly used, arterial calcium content does not reach cytotoxic levels observed in human. An overdose of vitamin D 3 results in a rapid arterial calcium overload. Using rats with arterial calcinosis and age- and gender-matched Wistar controls, we investigated whether EDDF has beneficial effect on blood vessels from animals with arterial calcinosis. Blood vessel functions were impaired in rats with arterial calcinosis, as indicated by decreased Ca 2+-ATPase activity, increased vasoconstrictor responses to alpha1 adrenoceptor agonist phenylephrine and increased ERK1/2 phosphorylation. Arterial calcium overload also impaired the morphological integrity of VSMCs. EDDF restored the abovementioned abnormalities caused by arterial calcinosis, and inhibited cell cycle progression of VSMCs induced by angiotensin II. In conclusion, EDDF may protect blood vessels from animals with arterial calcinosis, which is mediated by regulating calcium homeostasis, vascular reactivity and cell cycle progression as well as by improving morphological integrity of VSMCs.

Calorie restriction and cardiometabolic health

An epidemic of overweight/obesity and type 2 diabetes, caused by overeating nutrient-poor energy-dense foods and a sedentary lifestyle, is spreading rapidly throughout the world. Abdominal obesity represents a serious threat to health because it increases the risk of developing many chronic diseases, including cardiovascular disease and cancer. Calorie restriction (CR) with adequate nutrition improves cardiometabolic health, prevents tumorigenesis and increases life span in experimental animals. The purpose of this review is to evaluate the metabolic and clinical implications of CR with adequate nutrition in humans, within the context of data obtained in animal models. It is unlikely that information regarding the effect of CR on maximal life span in humans will become available in the foreseeable future. In young and middle-aged healthy individuals, however, CR causes many of the same cardiometabolic adaptations that occur in long-lived CR rodents, including decreased metabolic, hormonal and inflammatory risk factors for diabetes, hypertension, cardiovascular disease and cancer. Unraveling the mechanisms that link calorie intake and body composition with metabolism and aging will be a major step in understanding the age-dependency of a wide range of human diseases and will also contribute to improve the general quality of life at old ages.

Sodium nitroprusside-induced tissue hypoxia and its correction with plant preparations

Tissue hypoxia caused by acute or repeated administration of sodium nitroprusside to experimental mice induced changes in hemopoietic and lymphoid organs. Isolated flavonoids and alkaloids as well as complex plant preparations abolished the negative consequences caused by the hypoxant and prolonged the lifespan of experimental animals.