Effect of atropine, PGF2 alpha and cimetidine on the beta-carotene induced cytoprotection in ethanol-treated rats

The aim of the study was to evaluate the influence of atropine, PGF2 alpha and cimetidine on the gastric cytoprotective effect of beta-carotene. Mucosal damage was produced by intragastric (i.g.) addition of 96% ethanol in CFY-strain rats of both sexes weighing 180-220 g. Gastric cytoprotection caused by i. g. pretreatment with 1.0 mg/kg beta-carotene 30 minutes before ethanol administration, was observed after 1 hour. Atropine (0.5 mg/kg), cimetidine (50 mg/kg) and PGF2 alpha (200 micrograms/kg) were given intraperitoneally (i.p.) 30 minutes before ethanol administration with and without beta-carotene and the changes in the number and severity of the gastric ulcers were detected. PGF2 alpha did not influence the gastric cytoprotective effect of beta-carotene meanwhile it was inhibited by atropine and markedly by cimetidine. Deleterious effect of cimetidine on the beta-carotene-induced cytoprotection may be explained perhaps by the adverse effect of the two compounds on ATP-cAMP transformation hereby counteracting one another, but more data are needed to the better understanding of drug interactions relating to mucosal cytoprotection.     

Changes in Histamine Metabolism in the Mouse Hypothalamus Induced by Acute Administration of Ethanol

The effect of acute ethanol administration on histamine (HA) dynamics was examined in the mouse hypothalamus. The steady-state level of HA did not change after intraperitoneal administration of ethanol (0.5-5 g/kg), whereas the level of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, increased when 3 and 5 g/kg of ethanol was given. Pargyline hydrochloride (80 mg/kg, i.p.) increased the level of t-MH by 72.2% 90 min after the treatment. Ethanol at any dose given did not significantly affect the t-MH level in the pargyline-pretreated mice. Decrease in the t-MH level induced by metoprine (10 mg/kg, i.p.), an inhibitor of HA-N-methyltransferase, was suppressed by ethanol (5 g/kg), thereby suggesting inhibition of the elimination of brain t-MH. Ethanol (5 g/kg) significantly delayed the depletion of HA induced by (S)-alpha-fluoromethylhistidine (50 mg/kg, i.v.), a specific inhibitor of histidine decarboxylase. Therefore, a large dose of ethanol apparently decreases HA turnover in the mouse hypothalamus.     

Interrelationships between the gastric cytoprotective effects of vitamin A and beta-carotene and the gastric mucosal superoxide dismutase activity in rats

Gastric mucosal damage was produced in rats by the intragastric administration of 96% ethanol or 0.6 M HCl, according to the method of Robert et al. Vitamin A or beta-carotene, in doses of 10 mg/kg, given intragastrically 30 min before the administration of the necrotizing agents. The animals were killed 1 hr after the administration of the necrotizing agents. The following experimental parameters were studied, without and with application of vitamin A and beta-carotene; number of gastric lesions (ulcers); severity of gastric mucosal lesions (ulcers); gastric mucosal superoxide dismutase (SOD) activity. It was found that; vitamin A and beta-carotene, in doses of 10 mg/kg, are able to prevent significantly both the number and severity of gastric mucosal lesions (ulcers) produced by the application of 96% ethanol or 0.6 M HCl; the significant increase of ethanol-induced gastric mucosal SOD activity can be inhibited by the application of vitamin A and beta-carotene; vitamin A and beta-carotene are capable of preventing the development of gastric mucosal lesions (ulcers) produced by the intragastric administration of 0.6 M HCl, while these agents fail to compensate for the HCl-induced decrease of gastric mucosal SOD activity. It has been suggested that; vitamin A and beta-carotene are gastric cytoprotective agents; the ulcer preventive effects of vitamin A and beta-carotene are partly dependent on their scavanger behaviour.     

Morphology of ferret subcutaneous adipose tissue after 6-month daily supplementation with oral beta-carotene

Adipose tissue is an important retinoid depot and retinoids are known to influence white and brown adipocyte metabolism. Identifying nutrients that can affect the biological activity of the adipose organ would be of great medical interest in the light of the current obesity epidemic and related disorders in developed countries. The vast majority of mammal studies of chronic administration of oral beta-carotene have used murine models, while few have employed mammals exhibiting uptake and processing of intestinal beta-carotene similar to those of humans. While rodents transform practically all ingested beta-carotene into retinol, in ferrets, as in humans, part of the beta-carotene is absorbed and released into the circulation intact. We studied the effects of 6-month daily administration of two doses of oral beta-carotene (0.8 or 3.2 mg/kg/day) on ferret body weight, size of body fat depots, and, using morphological and morphometric methods, on subcutaneous (inguinal) white adipose tissue (WAT). Because of the oral mode of administration, liver, stomach, and small and large intestine were also studied. Control animals received the vehicle. Data show that at the end of treatment the higher dose induced significantly higher body weight compared with controls and significantly higher inguinal fat depot compared with animals treated with the lower dose. In addition, chronic treatment with beta-carotene induced a dose-dependent hypertrophy of white adipocytes and increased neoangiogenesis in subcutaneous WAT in all treated ferrets. Vasculogenesis was independent of adipocyte hypertrophy. We also found focally evident liver steatosis in the ferrets treated with the higher dose of beta-carotene. The other gastrointestinal tract organs studied were not significantly different from those of control animals.     

The key-role of vagal nerve and adrenals in the cytoprotection and general gastric mucosal integrity.

BACKGROUND: Our laboratory group observed earlier that the gastric mucosal cytoprotective effect of prostacyclin (PGI(2)) disappeared after surgical vagotomy in rats. Similarly to this, the beta-carotene induced gastric cytoprotection disappeared in adrenalectomized rats too. AIMS: In these studies we aimed to investigate the possible role of vagal nerve and adrenals in the development of gastric mucosal lesions induced by exogenously administered chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers (vitamin A and beta-carotene). METHODS: The observations were carried out in fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH; 25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in intact, surgically bilaterally vagatomized, and adrenalectomized rats without or with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week). The gastric mucosal protective effect of antisecretory doses of atropine (0.1-0.5-1.0 mg/kg i.g.) and cimetidine (10-25-50 mg/kg i.g.), and vitamin A and beta-carotene (0.01-0.1-1.0-10 mg/kg i.g.) was studied. The number and severity of mucosal gastric lesions was numerically or semiquantitatively measured. In other series of observations the gastric acid secretion and mucosal damage were studied in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy. RESULTS: It was found that: (1) the chemical-induced gastric mucosal damage was enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous secretion of gastric acid, and the development of mucosal damage can be prevented by surgical vagotomy; (2) the gastric cyto- and general protection produced by the drugs and scavengers disappeared in vagotomized and adrenalectomized rats; (3) the gastric mucosal protective effects of drugs and of scavengers returned after sufficient glucocorticoid supplementation of the rats. CONCLUSION: It has been concluded that the intact vagal nerve and adrenals have a key role in the gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and general mucosal protection.     

Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.     

Optimization of tumour radiotherapy: Part V--Radiosensitization by 2-deoxy-D-glucose and DNA ligand Hoechst-33342 in a murine tumour

Radiosensitizing effects of combination of a minor groove DNA ligand, Hoechst-33342, with the glucose analogue and inhibitor of glycolysis, 2-deoxy-D-glucose (2-DG) have been investigated in Ehrlich ascites tumour (EAT) bearing mice following focal irradiation of the tumour with 60Co gamma-rays. Treatment-induced tumour growth delay and tumour free animal survival were evaluated as parameters of radiation response. Focal irradiation of the tumour with a single fraction of 10 Gy induced a moderate delay in tumour growth but did not lead to complete regression in any of the tumours. Intravenous administration of H-342 1 hr before irradiation enhanced radiation-induced growth delay in a dose dependent manner. Complete regression of the tumour was observed only at a dose of 10 mg/kg body wt, leading to a cure (tumour free survival for more than 100 days) rate of 55%. Administration of 2-DG (2 g/kg body wt; i.v.), immediately before irradiation significantly enhanced radiation-induced growth delay and resulted in a cure rate of 45%. In combination with this dose of 2-DG (2 g/kg body wt), H-342 at a lower dose (5 mg/kg body wt) significantly enhanced the cure rate to 66%. H-342 or 2-DG given alone or in combination at the doses investigated here did not show any significant effects on the unirradiated tumour.     

环磷酰胺诱导小鼠血小板减少症模型的建立(英文）

比较由环磷酰胺两种不同给药方式诱导小鼠血小板减少症模型的效果,并对效果较稳定的一种给药方式进行最佳造模剂量摸索,以期确定一个造模效果较好,毒副作用较低,利于观察治疗药物疗效的血小板减少症模型。模型A组,第1天尾静脉注射环磷酰胺200 mg/kg,然后连续6 d,每天1次以维持剂量30 mg/kg腹腔注射环磷酰胺。模型B组,按150 mg/kg皮下注射环磷酰胺,每天1次,连续3 d。结果显示模型B组造模效果较好,故以模型B组给药方法进行剂量摸索实验。由第7天的血小板计数可知环磷酰胺低（100 mg/kg）、中（120 mg/kg）、高（140 mg/kg）剂量均可引起血小板减少症,而低剂量组与其他组比较有高效低毒的特点,更有利于观察治疗药物的作用,可用于具有升血小板作用药物的药效学研究     

Effect of beta-carotene on the inhibition of lung metastasis in mice.

Effect of beta-carotene on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. Simultaneous administration of the compound after tumor induction produced a significant reduction (71.36%) in tumor nodule formation. Increased lung collagen hydroxyproline (22.37 microg/mg protein) in the metastasized lungs of control animals compared to the normal animals (0.95 microg/mg protein) was significantly reduced (4.19 microg/mg protein) in the beta-carotene treated animals. High amount of uronic acid (355.83 microg/100mg tissue ) in the metastasized control animals was significantly reduced (87.87 microg/100 mg tissue) in the animals treated with beta-carotene. Lung hexosamine content also was inhibited significantly in the beta-carotene treated animals (1.58 mg/100 mg lyophilized tissue) compared to the untreated control animals (4.2 mg/100 mg lyophilized tissue). The elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with beta-carotene. Beta carotene treated animals were survived up to 69 days. Histopathology of the lung tissue also correlated with the above parameters and life span of the drug treated animals. Our results reveal the antimetastatic activity of beta-carotene which are abundantly present in green plants, vegetables and fruits.     

N-acetil-l-cysteine and 2-amino-2-thiiazoline N-acetyl-l-cysteinate as a possible cancer chemopreventive agents in murine models

The aim of this study was to investigate N-acetyl-cysteine (NAC) and its 2-amino-2-thiazoline salt (NACAT) as potential chemopreventive agents on experimentally induced lung tumours by urethane (U) in mice. Female BALB/c mice were used. U was given by intraperitoneal injections during 2 weeks (single dose - 10 mg/mouse, total - 50 mg/mouse). Mice were treated daily per os with NAC 1/10 LD50, NACAT 1/10 or 1/100 LD50 starting 2 weeks prior U administration, then during U treatment and thereafter for 2 months. The duration of experiment was 4 months. The results showed that NAC (1000 mg/kg) reduced the lung tumour incidence to 30% that of controls, P < or = 0.05. Most effective of NACAT was 100 mg/kg dose; it reduced an average of lung adenomas per mouse by 26%, P < or = 0.05, but lower dose (10 mg/kg) was less effective. In order to achieve similar chemopreventive effect (approximately 30%) on mice, it is necessary to use 0.38 mM/kg of NACAT or 6.13 mM/kg of NAC. It means that 16 times less of NACAT is required, if calculated by molar concentration. In general, NAC and NACAT have a moderate chemopreventive effect on lung tumorigenesis induced by urethane in mice.     

Effects of the kappa opioid receptor antagonist MR-2266-BS on the acquisition of ethanol preference

Using a paradigm by which rats forced to drink a weak ethanol solution (2.5% w/v) (conditioning session) develop ethanol preference in consecutive retention testing days, the effects of the administration of the kappa opioid antagonist MR-2266-BS, prior to or after the forced ethanol session, were studied. Pre-conditioning subcutaneous (s.c.) administration of 1 mg/kg of MR-2266-BS induced a decrease in subsequent ethanol consumption without significantly modifying the acquisition of ethanol preference. Post-conditioning administration of MR-2266-BS (0.1, 1, 5 or 10 mg/kg) induced both a dose-dependent reduction in ethanol consumption and in preference throughout the three following days. The results of the present study provide further support of the involvement of kappa-type opioids on drinking behavior, and suggest that kappa receptors may be involved in the consumption and development of preference to ethanol.     

Effects of high density lipoprotein containing high or low beta-carotene concentrations on progesterone production and beta-carotene uptake and depletion by bovine luteal cells

Luteal cells were isolated from mid-luteal heifer ovaries by collagenase digestion. Cells were cultured with DMEM/Ham's F12 medium in serum pre-treated plastic culture dishes for periods of up to 11 days. As beta-carotene is almost completely insoluble in all polar solvents, it was added to cultures in either dimethyl sulphoxide (DMSO), tetrahydrofuran (THF) or as high-density lipoprotein (HDL) containing high or low beta-carotene concentrations. Medium was replaced after 24 h, thereafter medium was changed every 48 h. Treatment of cells with DMSO alone or with beta-carotene (5 micromol/l) in DMSO both resulted in significant (P<0.01) stimulation of progesterone production. beta-Carotene (5 micromol/l) in THF did not alter progesterone production but 50 micromol/l beta-carotene in THF resulted in significant inhibition (P<0.02) of progesterone production on days 3 and 7. Cultures were also supplemented with bovine HDL preparations containing equal concentrations of cholesterol (25 microg/ml) but high or low beta-carotene (12.4 or 0.44 microg/mg of cholesterol). Both HDL preparations significantly stimulated progesterone production (P<0. 001) but the high beta-carotene HDL was significantly (P<0.02) more effective than the low beta-carotene HDL. However, when given together with bovine luteinizing hormone (bLH) or dibutyryl cAMP (dbcAMP), the high beta-carotene HDL stimulated progesterone production less than did the low HDL (P<0.01). Uptake and depletion of beta-carotene by luteal cells were also examined in culture. beta-Carotene supplementation increased luteal cell beta-carotene from an initial level of 373 ng per 10(6) cells to 2030 ng per 10(6) cells by day 6. In contrast, the levels in control cells decreased to 14% of starting values during the same period. Cells treated with HDL containing high beta-carotene on day 1 or days 1 and 3 were then incubated with or without bLH or dbcAMP for a further 2 days to investigate the effect of bLH and dbcAMP on depletion of beta-carotene by luteal cells. beta-Carotene depletion in the luteal cells was significantly higher (P<0.05) in LH- and dbcAMP-treated cells than in the control cells in both groups. These results indicate that the use of solvents such as DMSO or THF may have undesirable effects due to alteration of cell membrane permeability. Supplementation with bLH or dbcAMP may increase the metabolism of beta-carotene in luteal cells. bLH or dbcAMP together with high beta-carotene HDL may, when combined with the effect of increased beta-carotene metabolism, give less stimulation than with low beta-carotene HDL.     

Effects of beta-carotene and alpha-tocopherol on radical-initiated peroxidation of microsomes.

Rat liver microsomal membranes were exposed to either beta-nicotinamide adenine dinucleotide phosphate (NADPH), adenosine 5'-diphosphate (ADP), and Fe+3 or to azocompounds, and the antioxidant activities of beta-carotene and alpha-tocopherol were studied. Lipid peroxidation was monitored either by malondialdehyde (MDA) formation in the thiobarbituric acid assay at 535 nm or by hydroperoxide formation at 234 nm, after high-pressure liquid chromatography (HPLC) separation of phospholipid hydroperoxides. The radical initiators, water-soluble 2,2'-azobis(2-amidinopropane) (AAPH) and lipid-soluble 2,2'-azobis(2,4-dimethylvaleronitrile (AMVN), when thermally decomposed at 37 degrees C under air, produced a constant rate of lipid peroxidation in microsomes and lag times inversely related to their concentrations. Using 25 mM AAPH, beta-carotene suppressed lipid peroxidation at a concentration of 50 nmol/mg protein; using 24 mM AMVN, an inhibition of MDA formation was observed at a concentration of only 5 nmol/mg protein. Inhibition by beta-carotene did not produce a clearly defined lag phase. During AAPH-induced lipid peroxidation, beta-carotene was consumed linearly, and high levels of the antioxidant were still present at the end of 45 min of incubation. Using NADPH/ADP/Fe+3, protection by beta-carotene was observed at 10 nmol/mg protein. alpha-Tocopherol effectively suppressed both MDA and hydroperoxide formation in a dose-dependent manner when either NADPH/ADP/Fe+3 or azocompounds were used. These effects were observed at very low concentrations of the added alpha-tocopherol, ranging from 2 to 3 nmol/mg protein. When the lag times were measurable (AAPH and AMVN), they were directly proportional to the concentration of alpha-tocopherol and revealed the presence of endogenous antioxidants in the microsomal membranes. Different temporal relationships between the loss of alpha-tocopherol and lipid peroxidation were observed in relation to the prooxidant used. A substantial depletion of about 70% of endogenous alpha-tocopherol preceded the propagation phase when induced by the azocompounds, while only 20% of antioxidant disappeared at the beginning of the peroxidation when induced by NADPH/ADP/Fe+3. Although our results show that both beta-carotene and alpha-tocopherol suppress the peroxidation of microsomal membranes, their antioxidant efficacy is influenced by several factors, including the type of radical initiator involved and the site and rate of radical production.     

Beta-carotene as an inhibitor of benzo(a)pyrene and mitomycin C induced chromosomal breaks in the bone marrow of mice

Female mice of hybrid strain B6C3F1, 8-10 weeks old, were fed on powdered food with or without beta-carotene (100 mg/kg food). After 1 week of these diets, some of each group of mice were injected i.p. with either benzo(a)pyrene (150 mg/kg) in dimethyl sulfoxide, or mitomycin C (1 mg/kg) in distilled water. In the course of separate experiments, bone marrow samples were collected at various intervals after injection for analysis in the in vivo bone marrow micronucleus assay. At the time at which the maximum induction was observed, which coincided between experiments, the frequency of micronuclei induced by benzo(a)pyrene was reduced by 41-61% and that induced by mitomycin C was reduced by 44-71% in the presence of beta-carotene. Beta-carotene is widely distributed in plant material such as carrots and green leafy vegetables and, as such, is a component of the human diet. Our results suggest that beta-carotene provides significant protection against the genotoxicity of benzo(a)pyrene and mitomycin C.     

Thermal behavior of cores of human serum triglyceride-rich lipoproteins: a study of induced circular dichroism of beta-carotene

Induced circular dichroism (CD) of beta-carotene has been used to study the physical state in the cores of three classes of triglyceride-rich lipoproteins from human serum: intermediate-density lipoproteins (IDL) (1.006 less than d less than 1.019 g/mL) and subfractions of the d less than 1.006 g/mL lipoproteins of beta and pre-beta electrophoretic mobility. Effects on the physical state in the cores attributable to the ratio of triglycerides to cholesteryl esters and particle diameters were assessed by comparing the temperature-dependent CD spectra of beta-carotene with those of low-density lipoproteins (LDL). Lipoproteins were prepared from serum by sequential ultracentrifugation after the donors were given supplemental dietary beta-carotene (60 mg/day) for 2 weeks. The beta- and pre-beta-migrating d less than 1.006 g/mL lipoproteins were separated by starch block electrophoresis and were then individually separated into subfractions by agarose gel filtration chromatography. Between 7 and 30 degrees C, four subfractions of the beta-migrating d less than 1.006 g/mL lipoproteins and IDL exhibited reversible, temperature-dependent induced CD of beta-carotene, with contours similar to those of LDL but with smaller magnitudes and much broader transitions of the CD bands than those of LDL. In contrast, subfractions of the pre-beta-migrating d less than 1.006 g/mL lipoproteins showed no detectable induced CD of beta-carotene. These results show that the cores of triglyceride-rich lipoproteins can exist in some ordered state between 7 and 30 degrees C if they have a relatively low ratio of triglycerides to cholesteryl esters (mass ratio less than 1.6) and relatively small particle diameter (less than 60 nm).     

Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticles

This study addresses issues of relevance for siRNA nanoparticle delivery by investigating the functional impact of tumor-specific targeting and dosing schedule. The investigations are performed using an experimental system involving a syngeneic mouse cancer model and a theoretical system based on our previously described mathematical model of siRNA delivery and function. A/J mice bearing subcutaneous Neuro2A tumors approximately 100 mm(3) in size were treated by intravenous injection with siRNA-containing nanoparticles formed with cyclodextrin-containing polycations (CDP). Three consecutive daily doses of transferrin (Tf)-targeted nanoparticles carrying 2.5 mg/kg of two different siRNA sequences targeting ribonucleotide reductase subunit M2 (RRM2) slowed tumor growth, whereas non-targeted nanoparticles were significantly less effective when given at the same dose. Furthermore, administration of the three doses on consecutive days or every 3 days did not lead to statistically significant differences in tumor growth delay. Mathematical model calculations of siRNA-mediated target protein knockdown and tumor growth inhibition are used to elucidate possible mechanisms to explain the observed effects and to provide guidelines for designing more effective siRNA-based treatment regimens regardless of delivery methodology and tumor type.     

The modifying effect of beta-carotene on gamma radiation-induced elevation of oxidative reactions and genotoxicity in male rats

The aim of the present work was to evaluate the modulatory role of beta-carotene on the radiation-induced changes in certain biochemical and cytogenetic parameters. beta-Carotene was given by gavage at a dose of 5 mg/kg body weight for 7 consecutive days before whole body gamma irradiation with 7 Gy (single dose). The levels of beta-carotene in plasma, thiobarbituric acid-reactive substances (TBARS) in plasma and liver, the activities of superoxide dismutase (SOD) and catalase in blood and liver were the selected parameters. Furthermore, the frequency of micronuclei (MN) of polychromatic erythrocytes (PCEs), normochromatic erythrocytes (NCEs), the ratio of PCEs/NCEs and the mitotic index (MI) of bone marrow cells were also evaluated. The biochemical and cytogenetic determinations were carried out 1, 24, and 72 h after radiation exposure.The results obtained revealed that administration of beta-carotene pre-irradiation significantly inhibited the decrease in plasma beta-carotene, significantly reduced the levels of TBARS in plasma and liver. Significant protection of the radiation-induced changes in the activities of SOD and catalase was also recorded in the blood and liver of beta-carotene-treated and -irradiated rats. beta-Carotene resulted in significant inhibition in the frequency of radiation-induced MN, as well as in the ratio of PCEs/NCEs and the MI of bone marrow cells. These results suggest that beta-carotene as a natural product with its antioxidant capacity and capability of quenching singlet oxygen, could play a modulatory role against the cellular damage affected by free radicals induced by whole body irradiation.     

Effect of injection of beta-carotene or vitamin E and selenium on fertility of lactating dairy cows

Experiments tested whether supplemental antioxidants improved fertility. To test effects of beta-carotene, cows in a hot environment were injected with prostaglandin F2 alpha (PGF2 alpha) and were given 3 injections, i.m., of 800 mg beta-carotene or saline at Days -6 and -3 before the anticipated date of insemination and at insemination (n = 37-41 inseminated cows/group). There was no effect of beta-carotene on the proportion of cows detected in estrus following PGF2 alpha, timing of estrus after PGF2 alpha injection or pregnancy rate in inseminated cows. In a second trial, cows in a temperate climate received intramuscular injections of vitamin E (500 mg) and selenium (50 mg) at 30 d post partum (n = 97) or were untreated controls (n = 89). Treatment did not affect interval from calving to first insemination or the proportion of cows pregnant at first service, but it increased the pregnancy rate at second service (69.8 vs 52.1%; P = 0.07) and reduced services per conception (1.7 vs 2.0; P < 0.05) and interval from calving to conception (84.6 vs 98.1; P < 0.05). Thus, injection of vitamin E and selenium increased fertility in cattle that did not become pregnant at first service.     

Effect of beta-carotene administration on reproductive function of horse and pony mares

The objective of this study was to determine whether supplemental beta-carotene would influence reproductive function in mares maintained on spring and summer pastures and to characterize plasma carotene concentrations during the estrous cycle. Carotene concentrations in plasma did not vary with day of estrous cycle (P = 0.7455). Mares receiving every other day injections of beta-carotene (400 mg; n = 4) or saline (10 ml; n = 4) during proestrus/estrus did not differ in plasma estradiol (E(2)) concentrations (P = 0.6313), follicle development (P = 0.8068), or plasma progesterone (P(4)) concentrations during the following diestrus (P = 0.4954). Moreover, no differences in plasma P(4) concentrations (P = 0.9047) were detected between mares receiving every other day injections of beta-carotene (400 mg; n = 4) or saline (10 ml; n = 4) during diestrus. However, administration of beta-carotene raised plasma carotene concentrations relative to controls when injected during proestrus/estrus (P = 0.0096) and diestrus (P = 0.0099). Pregnancy rates (P = 0.4900) and number of cycles required for pregnancy (P = 0.2880) were similar for mares administered injections of saline (10 ml; n = 37), beta-carotene (400 mg; n = 37), vitamin A (160,000 IU; n = 38), or vitamin A + beta-carotene (160,000 IU + 400 mg; n = 43), on the first or second day of estrus and on the day of breeding. Therefore, these results collectively suggest that supplemental beta-carotene does not affect the reproductive function of mares fed adequate dietary carotene. Whether supplemental beta-carotene would enhance reproductive function in mares on low carotene diets warrants further investigation.     

The benzodiazepine receptor inverse agonists beta-CCM and RO 15-3505 both reverse the anxiolytic effects of ethanol in mice

The antagonistic effects of the benzodiazepine receptor inverse agonist beta-CCM (1 mg/kg) and of the partial inverse agonist RO 15-3505 (3 mg/kg) on the anxiolytic properties of ethanol (1 g/kg) in mice confronted with a light/dark choice procedure and with the staircase test were investigated. Both drugs reversed the effects of ethanol on some of the behavioral parameters, but beta-CCM alone elicited anxiogenic intrinsic effects. RO 15-3505 induced seizures in mice treated with a subconvulsant dose of pentylenetetrazole, the most efficient doses being 3 and 6 mg/kg. These data indicate that beta-CCM and RO 15-3505 can reverse some of the anxiolytic effects of ethanol, acting probably to oppose GABA function via the benzodiazepine receptor.