The use of mexamine to reduce radiation injuries during embryogenesis of Wistar rats

In experiments with 330 Wistar rats experiencing their first pregnancy and 1430 neonatal rats of the first generation a study was made on the toxicity and radioprotective efficiency of a single subcutaneous injection of 10 mg/kg mexamine on days 3, 11 and 19 of pregnancy. The agent caused various abnormalities in pregnancy, delivery and postnatal development of the offspring of nonirradiated animals, and it was almost ineffective when used for the prevention of radiation damages during the antenatal ontogenesis.     

The action of potassium orotate in prophylactic and therapeutic administration to irradiated rats

A study was made of the radioprotective and therapeutic effect of potassium orotate on rats subjected to whole-body gamma-irradiated with doses of 11, 9 and 4 Gy. The preparation exerted a radioprotective action when administered intraperitoneally 60 min before irradiation as was estimated with a reference to the survival rate and leukocyte level in the peripheral blood. Fron the analysis of the peripheral blood consumption it was inferred that potassium orotate weakened the radiation damage and enhanced the recovery processes during the postirradiation period.     

Radioprotection by a herbal preparation of Hippophae rhamnoides, RH-3, against whole body lethal irradiation in mice.

PURPOSE: Hippophae rhamnoides L. has been well documented to have anti-oxidative, immunostimulative and regenerative properties and therefore a herbal preparation of H. rhamnoides coded as RH-3 was investigated for its radioprotective action. MATERIALS AND METHODS: RH-3 was administered intraperitonially (i.p.) to mice 30 minutes before whole body irradiation and whole body survival, spleen Colony forming units (CFU) and haematological parameters were studied. To investigate free radical scavenging and antioxidant potential, Fenton reaction, radiation mediated OH radical scavenging and chemically generated superoxide anions scavenging were studied in vitro while inhibition of lipid peroxidation was studied in liver homogenate of mice. RESULTS: A dose of 30 mg/kg body weight of RH-3 rendered 82% survival as compared to no survival in irradiated control. The endogenous CFU counts in mouse spleen on 10th post-irradiation day with and without RH-3 demonstrated radioprotective effect. Various hematological parameters also corroborated the radioprotective effect of RH-3. In a dose dependent manner, RH-3 inhibited Fenton reaction and radiation mediated generation of hydroxyl radicals in vitro, superoxide anion mediated Nitroblue tetrazolium (NBT) reduction and FeSO4 mediated lipid peroxidation in liver. CONCLUSION: Free radical scavenging, acceleration of stem cell proliferation and immunostimulation are the radioprotective attributes, which require further investigations.     

Pregnancy influence on the vascular interactions between nitric oxide and other endothelium-derived mediators in rat kidney

Peripheral vascular resistance and sensitivity to circulating pressor and vasoconstrictor agents are blunted during pregnancy. This has been mainly attributed to an increased production of endothelium-derived mediators. The objective of this work was to evaluate if pregnancy changes the relative participation of nitric oxide (NO) and prostaglandins (PG) in respect to the modulation of the increases in renal perfusion pressure induced by phenylephrine (Phe). Dose-response curves were made with gradually increasing doses of Phe using an isolated kidney preparation in the presence of a NO synthase (NOS) inhibitor (L-NAME, 1 microM), a PG-synthesis inhibitor (indomethacin, 1 microM), both, or neither. Also, renal cyclooxygenase (COX-1 and COX-2) and endothelial NOS (eNOS) expression was determined using PCR. The experiments were done in kidneys from nonpregnant and pregnant rats. Our results showed that the relative participation of renal vasoactive mediators seems to change during pregnancy. We found the presence of a COX-1-dependent vasoconstrictor in the middle of pregnancy that was not found in nonpregnant rats. Our results also suggest that there is increased participation of another renal vasodilator substance, the effect of which is observed when NO or PG synthesis is inhibited during late pregnancy. In addition, an apparent interaction between renal eNOS and COX-1 expression was observed: eNOS expression was diminished, while COX-1 was increased during the 2nd week of pregnancy. In contrast, in kidneys from the 3rd week of pregnancy, the expression of these two enzymes was similar.     

Sodium Selenite Improves Folliculogenesis in Radiation-Induced Ovarian Failure: A Mechanistic Approach

Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in-vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma-radiation (3.2 Gy, LD₂₀), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles’ maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.     

Preimplantation embryo development and serum steroid levels in immature rats induced to ovulate or superovulate with pregnant mares' serum gonadotropin injection or follicle-stimulating hormone infusions

Follicular stimulation protocols using pregnant mares' serum gonadotropin (PMSG) or a follicle-stimulating hormone (FSH) preparation were compared to evaluate the yield and quality of embryos obtained from immature rats. Rats received a superovulatory dose of PMSG (401U), a nonsuperovulatory dose of the same gonadotrophin (4 IU), or a continu ous s.c. infusion over a 72-h period with a purified FSH preparation containing an opti mum ratio of luteinizing hormone (LH): FSH (FSH-hCG). The females were caged with fertile males on the evening of the 3rd day of gonadotropin treatment and scored for the occurrence of mating on the next morning; subgroups were killed on days 1–4 of preg-nancy. High fertilization rates were observed in rats treated with 4 IU PMSG (84.1%) and in rats infused with FSH-hCG (91.0%); however, a much lower fertilization rate was observed following treatment with 40 IU PMSG (41.5%). From median ovulation rates of 9 and 79 in rats treated with 4 IU PMSG and in rats infused with FSH-hCG, medians of 8 and 69 embryos, respectively, were recovered from reproductive tracts flushed on day 4 of pregnancy, from which 75% were morulae or blastocysts; in contrast, from a median ovu lation rate of 42.5, a median of only 12 embryos was recovered on day 3 of pregnancy following superovulation with 40 IU PMSG of which 80% were degenerate ova. Serum steroid profiles during the first 4 days of pregnancy differed significantly among treatment groups, the major differences being in substantially elevated levels of estradiol and andro-gens on days 1–3 in rats receiving the high (40 IU) dose of PMSG. Levels of these steroids in rats superovulated with the FSH-hCG infusion regimen were only marginally elevated above levels observed in rats treated with the low (4 IU) nonsuperovulatory dose of PMSG. Consistent with high ovulation rates, serum progesterone levels rose to considera bly higher levels during the period in both superovulated groups than in animals receiving the low, nonsuperovulatory dose of PMSG. This work describes a novel method to superovulate rate (FSH-hCG) leading to high yields of normally developing embryos at all preimplantation stages and illustrates the close association between high yield of emyryos and low levels of circulating andorgens and estradiol-17β during the preimplantation period.     

The features of sleep homeostasis in pregnant rats

To investigate the effects of short-term sleep deprivation on the sleep pattern during pregnancy, cortical and hippocampal EEG and locomotor activity were recorded within 24-hours in a "disk-over-water" paradigm in 18 Wistar rats. Rats were adapted to experimental situation and were able to move across the rotating disk without falling in water. Then a polysomnogram was recorded for 3 sequential days in the control group 1 (n = 12) without disk rotation. On the next day non-pregnant rats (experimental group 1, n = 6) were subjected to the sleep deprivation procedure with a pre-set program of disk rotation from 11:00 to 14:00 during 3 sequential days. Other 6 rats (experimental group 2) were subjected to sleep deprivation on the 5-7th day of pregnancy. EEG and locomotor activity were also constantly recorded during the sleep deprivation procedure. In control group 2 (n = 6, without sleep deprivation), a polysomnogram was recorded on the 5-7th day of pregnancy. As compared to non-pregnant rats, sleep intensity of pregnant rats increased during the first hours after the deprivation, and a considerable rebound of REM sleep took place. Sleep pattern during the off-light 12 hours remained unchanged. The results suggest that homeostatic compensation of sleep deprivation effects in rats on the first week of pregnancy is more efficient than in control non-pregnant animals.     

Radioprotective effectiveness and toxicity of 4,5-disubstituted tryptamines

In experiments on mice a study was made of different substituents in the 4th position of the indole ring of 5-methoxytryptamines (5-MOT) on toxicity and radioprotective efficiency of the compounds of this class. It was shown that the administration of the amino-group to a mexamine molecule increased the preparation toxicity; the nitro-group somewhat diminished the toxic properties, and the acetylamino group did not change 5-MOT toxicity. A 5-MOT derivative with a nitro group possessed the strongest radioprotective action. The radioprotective efficiency of these compounds persisted for 1-2 h.     

The modifying action of Sophora japonica and an antioxidant vitamin complex on acute radiation injury to the body]

In experiments with mongrel male rats exposed to whole-body gamma-radiation (7, 9 and 11 Gy) the radioprotective effect of enterally administered Sophora japonica and its combination with an antioxidant vitamin complex was investigated. The radioprotective agents applied were shown to produce a synergistic effect.     

Comparative characteristics of the modification of radiosensitivity of mice and rats by a hypoxic mixture

A comparative study was made of changes in radiosensitivity of mice and rats given hypoxic mixtures (GHM) containing 6 to 15% of oxygen. The radioprotective effect of the GHM was more pronounced in mice than rats. The dependence of the radioprotective effect of the GHM on the oxygen content was well approximated by the equations: (Formula: see text). In experiments on rats, the oxygen content of 13.8% was shown to be a threshold the exceeding of which removed the modifying effect of the GHM.     

Radioprotective properties of indralin combined with cystamine and mexamine

The study of indralin radioprotective properties at its joint application with cystamine and mexamine was carried out in the experiments on inbred mice and rats. The mice and rats were exposed to whole-body y-irradiation at a dose of 9.0 and 9.5 Gy, correspondingly. A combined parenteral administration ofindralin and cystamine at a dose of 25 mg/kg showed ponentiaton of indralin radioprotective properties up to a level of the ED50 effect versus the absence of or a weak radioprotective effect in the case of their separate application. In the experiments on rats, indralin (50 mg/kg) and mexamine (12 mg/kg) injected intraperitoneally almost completely eliminated the animal mortality from the intestinal syndrome of acute radiation sickness amounting in the control radiation group to 60% on the 7th day after exposure to radiation at a dose of 9.5 Gy. However, at the above conditions, radioprotectors at these doses had a low-level radioprotective action at the onset of the bone marrow syndrome of acute radiation sickness. Combined application of indralin and mexamine at the same doses and at the same conditions led to a radiation protection 50% as high as in the case when radioprotectors were applied separately at a double dose.     

Effect of the gaseous hypoxic mixture GHM-10 on the radiosensitivity of the fetus and the development of offspring

A gas hypoxic mixture containing 10 percent of O2 and 90 percent of N2 was shown to exert a radioprotective action on pregnant rats and young rats of the first generation if animals were exposed to ionizing radiation during the periods of preimplantation, organogenesis and fetus development. The effect depended on the radiation dose and the period of the intrauterine development of fetus.     

Radioprotective properties of a Co(III) biocomplex

In experiments with rats and mice irradiated with doses of 5 and 8.5 Gy respectively, the radioprotective properties of a coordination combination Co(III) with bioactive ligands have been investigated by the results of the hematological analysis, the indices of erythrocyte and leucocyte electric conductivity, average life, survival rate, and beta coefficient showing a probability of protecting the organism against fatal effect of ionizing radiation. The preparation has either therapeutic or protective action depending on the animal species and radiation dose.     

Radioprotective properties of oxolinic acid

Oxolinic acid was shown to produce a radioprotective effect on mice and a therapeutic radioprotective action on rats and hamsters. As to radioprotective efficiency, oxolinic acid is inferior to such known sulfur-containing agents as indolylalkylamines and alpha-adrenomimetics. But oxolinic acid has an important advantage over them, that is, the increase in radioresistance it induces persists for several hours. The radioprotective effectiveness of oxolinic acid prompts that it is expedient to search for new radioprotective preparations among specific inhibitors of DNA polymerase of replicative synthesis.     

Manifestation of oxygen effect during normobaric hypoxic hypoxia in the intrauterine and postnatal developmental periods]

The experiments on rats have shown that hypoxic gas mixture containing 10% of oxygen and 90% of nitrogen (HGM-10) under normobaric conditions exerts a highly reliable radioprotective effect on progeny when 11-day pregnant animals are exposed to total irradiation (60Co, 20 Gy). As distinct from the known radioprotector, mexamine, (5-methoxytryptamine), HGM-10 has a pronounced radioprotective effect during the first days (1-5) after birth. Radioresistance of new-born rats correlates with the level of pO2 in the tissues which progressively decreases with respiration of HGM-10 and remains unchanged after mexamine (10 mg/kg) introduction.     

Differential regulation of apoptosis in the corpus luteum of pregnancy and newly formed corpus luteum after parturition in rats

Apoptosis contributes to luteal regression in many species. In the postpartum rat, there are two different types of corpora lutea (CL) in the ovary: CL of pregnancy (CLP) and newly formed CL (NCL). To investigate the regulation of apoptosis in the two different types of CL during luteal regression, apoptosis and caspase-3 activity were examined in the CL obtained on Days 7, 15, and 21 of pregnancy and Days 0, 1, 3, 5, 7, and 9 postpartum. Furthermore, the effect of lactation on apoptosis in the CL was examined in two groups of postpartum rats: lactating rats that nurse more than 10 pups, and nonlactating rats that nurse no pups. Apoptotic cells were detected after Day 21 of pregnancy. In the CLP, remarkable increases in the number of apoptotic cells on Days 5 and 9 postpartum were observed in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the CLP were not consistent with those in number of apoptotic cells. In the NCL, an increase in apoptosis was found only on Day 5 postpartum in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the NCL were consistent with those in number of apoptotic cells. In conclusion, apoptosis is, at least in part, involved in luteal regression after parturition, and lactation appears to inhibit apoptosis. This study also suggests the presence of a caspase-3-independent mechanism for apoptosis in CLP regression in the rat.     

The antidepressant role of dietary long-chain polyunsaturated n-3 fatty acids in two phases in the developing brain

In this work we investigated the effect from fish oil (FO) supplementation, rich in n-3 fatty acids, on an antidepressant effect on adult rats in Phase A (supplementation during pregnancy and lactation) and phase B (supplementation during post-weaning until adulthood). During Phase A, female rats, used as matrix to obtain male rats, were divided in three groups: FO (daily supplemented), CF (coconut fat daily supplemented) and control (not supplemented). Our results showed that adult rats whose mothers were supplemented with FO during Phase A and rats supplemented during phase B demonstrated a significantly decreased immobility time when compared to control and CF groups. There was no difference in neither motor activity nor anxiety behavior in the three groups excluding false positive results. Our results suggest that n-3 fatty acids supplementation during Phases A and B had a beneficial effect on preventing the development of depression-like behavior in adult rats.     

Radiosensitivity during the irradiation of animals in an altered gaseous environment. A comparative study on mice and rats of the radiation-protective effect of oxygen-deficient gas mixtures

The radioprotective effect of gas hypoxic mixtures containing 5, 7, 8, 10 and 15% of oxygen on mice and rats was comparatively studied. The dependence of DMF upon oxygen concentration in the mixture was approximated by a hyperbolic function similar to the dependence of the radiomodifying effect of circulatory hypoxia caused by radioprotective agents of the indolylalkylamine series.     

Pregnancy and steroid hormones enhance the systemic and regional hemodynamic effects of calcitonin gene-related peptide in rats

Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide known to be involved in the regulation of vascular resistance. Several lines of evidence suggest that CGRP plays a role in the vascular adaptations that occur during normal pregnancy; however, the effects of exogenous CGRP on systemic and regional hemodynamics during pregnancy remain unknown. Therefore, the purpose of this study was to determine the hemodynamic effects of systemically administered CGRP in adult pregnant (Day 19) and ovariectomized (ovx) rats using the radioactive microsphere technique. In addition, we also used ovariectomized rats treated for 3 days with estradiol (E2), progesterone (P4), E2 + P4 in sesame oil, or oil only to assess if these hormones regulate the CGRP-induced hemodynamic changes. On the day of study, catheters were inserted into the left cardiac ventricle (through the right carotid artery), right jugular vein, and caudal tail artery. Hemodynamic studies using radioactive microspheres were then performed in conscious rats 3 h after recovery from anesthesia. Blood pressure and heart rate were continuously monitored, and left ventricular pressure was determined immediately prior to each microsphere injection. Microspheres labeled with either (141)Ce or (85)Sr were injected prior to and 2 min following the i.v. bolus injection of CGRP (270 pmol/kg body weight [BW]). Mean arterial pressure (MAP) and total vascular resistance in pregnant rats was lower than in ovx rats, and this was further decreased with an i.v. bolus injection of 270 pmol CGRP/kg BW. Cardiac output was elevated with further increases upon CGRP administration in pregnant but not in ovx rats. The CGRP-induced changes in MAP, total vascular resistance, and cardiac output in E2 + P4 -treated rats were similar to that observed in Day 19 pregnant rats, indicating that CGRP effects on these parameters during pregnancy may be modulated by steroid hormones. Both pregnancy and E2 + P4 treatment in ovx rats caused significant decreases in CGRP-induced resistance in mesenteric, coronary, and renal vasculature. Thus, the vasodilatory sensitivity to CGRP during pregnancy may be mediated through decreased total vascular resistance, particularly to coronary, mesenteric, and renal vascular beds. Thus, CGRP-induced vasodilatory effects may play a role in mediating vascular adaptations that occur during pregnancy and that steroid hormones may modulate these CGRP effects.