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Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction.

Use of herbal medicines among patients under cardiovascular pharmacotherapy is widespread. In this paper, we have reviewed the literature to determine the possible interactions between herbal medicines and cardiovascular drugs. The Medline database was searched for clinical articles published between January 1996 and February 2003. Forty-three case reports and eight clinical trials were identified. Warfarin was the most common cardiovascular drug involved. It was found to interact with boldo, curbicin, fenugreek, garlic, danshen, devil's claw, don quai, ginkgo, papaya, lycium, mango, PC-SPES (resulting in over-anticoagulation) and with ginseng, green tea, soy and St. John's wort (causing decreased anticoagulant effect). Gum guar, St. John's wort, Siberian ginseng and wheat bran were found to decrease plasma digoxin concentration; aspirin interactions include spontaneous hyphema when associated with ginkgo and increased bioavailability if combined with tamarind. Decreased plasma concentration of simvastatin or lovastatin was observed after co-administration with St. John's wort and wheat bran, respectively. Other adverse events include hypertension after co-administration of ginkgo and a diuretic thiazide, hypokalemia after liquorice and antihypertensives and anticoagulation after phenprocoumon and St. John's wort. Interaction between herbal medicine and cardiovascular drugs is a potentially important safety issue. Patients taking anticoagulants are at the highest risk.

Anticoagulants↗

Cholera toxin B subunit labeling in lamina II of spinal cord dorsal horn following chronic inflammation in rats.

We have investigated the effect of inflammation on the labeling pattern of cholera toxin B subunit (CTB)-conjugated horseradish peroxidase, an A-fiber marker, by an intra-sciatic nerve injection of the tracer. Following chronic inflammation in one hind paw in rats, there was substantial CTB labeling in lamina II of the spinal dorsal horn, which is normally absent. However, there was no change in the labeling pattern of wheat germ agglutinin or fluoride resistant acid phosphatase/thiamine monophosphatase, two C-fiber markers. The CTB labeling in lamina II after peripheral nerve injury has been interpreted as central sprouting of A-fibers or uptake of the tracer by injured C-fibers. Our results suggest that chronic inflammation and nerve injury may share some common mechanisms in generating allodynia and hyperalgesia.

Animals↗

Intron excision from tRNA precursors by plant splicing endonuclease requires unique features of the mature tRNA domain.

It has been proposed that yeast and Xenopus splicing endonucleases initially recognize features in the mature tRNA domain common to all tRNA species and that the sequence and structure of the intron are only minor determinants of splice-site selection. In accordance with this postulation, we show that yeast endonuclease splices heterologous pre-tRNA(Tyr) species from vertebrates and plants which differ in their mature domains and intron secondary structures. In contrast, wheat germ splicing endonuclease displays a pronounced preference for homologous pre-tRNA species; an extensive study of heterologous substrates revealed that neither yeast pre-tRNA species specific for leucine, serine, phenylalanine and tyrosine nor human and Xenopus pre-tRNA(Tyr) species were spliced. In order to identify the elements essential for pre-tRNA splicing in plants, we constructed chimeric genes coding for tRNA precursors with a plant intron secondary structure and with mature tRNA(Tyr) domains from yeast and Xenopus, respectively. The chimeric pre-tRNA comprising the mature tRNA(Tyr) domain from Xenopus was spliced efficiently in wheat germ extract, whereas the chimeric construct containing the mature tRNA(Tyr) domain from yeast was not spliced at all. These data indicate that intron secondary structure contributes to the specificity of plant splicing endonuclease and that unique features of the mature tRNA domain play a dominant role in enzyme-substrate recognition. We further investigated the influence of specific nucleotides in the mature domain on splicing by generating a number of mutated pre-tRNA species. Our results suggest that nucleotides located in the D stem, i.e. in the center of the pre-tRNA molecule, are recognition points for plant splicing endonuclease.

Arabidopsis↗

Toxin resistance and reduced secretion in a mouse L-cell mutant defective in herpes virus propagation.

The mouse L-cell mutant gro29 was selected originally for its inability to propagate herpes simplex virus; it shows severe defects in virus egress and the transport and processing of viral glycoproteins after infection. In this report, we show that uninfected gro29 cells display pleiotropic changes in protein secretion, oligosaccharide processing, and sensitivity to the toxins ricin and modeccin. Specifically, the rate of secretion of a nonglycosylated protein, human growth hormone, was reduced 70% in gro29 cells compared with the parental L cells. A direct measurement of the transport capacity of Golgi membranes in a cell-free assay suggests that gro29 cells contain less functional Golgi than parental cells. Despite this deficiency, N-linked oligosaccharides were processed efficiently in mutant cells, although there were differences in the structure of the mature forms. Lectin intoxication assays revealed that gro29 cells were cross-resistant to killing by the cytotoxic lectins ricin and modeccin, but not to wheat germ agglutinin, Ricinus communis agglutinin RCA120, or leucoagglutinin. Fluorescence labeling using fluorescein-conjugated lectins showed that uninfected gro29 cells expressed relatively few ricin-binding molecules, suggesting a possible mechanism for toxin resistance. These studies provide evidence that the processes of protein secretion, lectin intoxication, and herpes virus maturation and egress may share a common cellular component.

Animals↗

Effect of processing on Fusarium mycotoxins.

Mycotoxins are secondary metabolites produced by a wide variety of fungal species that contaminate food or feed. Fumonisins (FUM), deoxynivalenol (DON) and zearalenone (ZEN) are examples of common mycotoxins in grains that have been shown to affect human and/or animal health. Physical, chemical and biological methods have been used for decontaminating grains containing these toxins. Some treatments reduce the concentration of mycotoxins while others are ineffective. For example, removal of damaged grain by density segregation can reduce DON and ZEN concentrations in corn and wheat. In contrast, thermal processing is usually ineffective for reducing the FUM and ZEN content of foods. More work is needed to identify effective methods for detoxifying mycotoxin contaminated food.

Animals↗

Candidate gene identification of an aluminum-activated organic acid transporter gene at the Alt4 locus for aluminum tolerance in rye (Secale cereale L.).

Among cereal crops, rye is one of the most tolerant species to aluminum. A candidate gene approach was used to determine the likely molecular identity of an Al tolerance locus (Alt4). Using PCR primers designed from a wheat aluminum tolerance gene encoding an aluminum-activated malate transporter (TaALMT1), a rye gene (ScALMT1) was amplified, cloned and sequenced. Subsequently, the ScALMT1 gene of rye was found to be located on 7RS by PCR amplification using the wheat-rye addition lines. SNP polymorphisms for this gene were detected among the parents of three F(2) populations that segregate for the Alt4 locus. A map of the rye chromosome 7R, including the Alt4 locus ScALMT1 and several molecular markers, was constructed showing a complete co-segregation between Alt4 and ScALMT1. Furthermore, expression experiments were carried out to clarify the function of this candidate gene. Briefly, the ScALMT1 gene was found to be primarily expressed in the root apex and upregulated when aluminum was present in the medium. Five-fold differences in the expression were found between the Al tolerant and the Al non-tolerant genotypes. Additionally, much higher expression was detected in the rye genotypes than the moderately tolerant "Chinese Spring" wheat cultivar. These results suggest that the Alt4 locus encodes an aluminum-activated organic acid transporter gene that could be utilized to increase Al tolerance in Al sensitive plant species. Finally, TaALMT1 homologous sequences were identified in different grasses and in the dicotyledonous plant Phaseolus vulgaris. Our data support the hypothesis of the existence of a common mechanism of Al tolerance encoded by a gene located in the homoeologous group four of cereals.

Aluminum↗

Roles of novelty, generalization, and postingestive feedback in the recognition of foods by lambs.

Ruminants select foods higher in nutrients and lower in toxins than the average of what is available whether fed in confinement or foraging on pastures or wild lands. Our objective was to better understand how sheep learn to select the most nutritious foods when they concurrently ingest different foods. We hypothesized that novelty and generalization are two ways sheep discriminate among foods. The first experiment determined whether lambs offered two foods in a meal (one a novel-flavored food and the other a familiar food) acquired a preference for the novel-flavored food following an infusion of energy (starch) into the rumen. Lambs did not increase preference for the novel-flavored food when the amount of starch infused (150 g) was held constant (P > 0.05). However, when the amount of starch infused was made directly proportional to the amount of novel-flavored food ingested, lambs quickly formed a preference for the novel-flavored food (P < 0.001). The second experiment determined whether lambs generalized preferences from familiar to novel foods. Lambs fed coconut-flavored milo grain for 51 d subsequently preferred coconut-flavored straw to plain straw (P < 0.001). Conversely, lambs that were not fed coconut-flavored milo grain preferred plain to coconut-flavored straw (P < 0.001). Lambs infused with a source of energy (starch, 100 g/[lamb x d]) consumed more coconut-flavored straw and less plain straw than lambs that had no infusions or lambs infused with a toxin (LiCl, 100 mg/kg BW; P < 0.05). Lambs infused once with LiCl had the lowest preference for coconut-flavored straw (P < 0.05). Lambs conditioned with starch had the highest intakes of coconut-flavored straw, even after starch infusions were suspended (P < 0.1). When straw was replaced by an energy-dense food (wheat grain), all lambs equally preferred coconut-flavored grain to plain grain (P < 0.001). Collectively, our results suggest that lambs learned to prefer a novel-flavored food when the amount of energy reward was contingent on the amount of novel-flavored food ingested, and that they generalized from familiar to unfamiliar foods based on common flavor cues. Once generalization occurred, postingestive feedback from nutrients and toxins calibrated preference according to the food's utility.

Animals↗

[Electron microscopic cytochemical study on lectin binding sites in the epiphyseal cartilage-plate of rabbit tibia].

Lectin is a common name given to a certain group of hemagglutinating proteins found primarily in plant seeds, which bind specifically to the branching sugar molecules of glycoproteins and glycolipids of the surface of the cells. The author selected 3 kinds of lectin among others. Those were concanavalin A (Con A) which specifically binds to the alpha-D-mannose, wheat germ agglutinin (WGA) which binds to N-acetyl glucosamine, and peanut agglutinin (PNA) which binds to beta-D-galactosamine. The localization of these lectins was examined in order to obtain any information on the process of the proteoglycan synthesis during the cellular differentiation in the epiphyseal cartilage-plate of the rabbit. The binding sites of Con A were determined by conjugating horse radish peroxidase as a marker in case of optical microscopic observations. For the purpose of electron microscopic observations, lectins were marked with gold colloidal particles. Most Con A was found in the rough surfaced endoplasmic reticulum, while a part of them was bound to the cis side of the Golgi apparatus. In the cellular column of the cartilage, Con A was increasingly abundant from the younger proliferating stage, through the maturing stage to the stage of hypertrophy, and diminished abruptly at the stage of provisional calcification. These observations were coincided with the degree of development of the endoplasmic reticulum during the maturation of cartilage cells. These findings suggest that alpha-D-mannose is indispensable to the initial stage of proteoglycan synthesis. WGA was observed from the cis side to the intermediate layer of Golgi apparatus, but not at the trans side of the Golgi apparatus, nor in the endoplasmic reticulum. These findings suggest that N-acetyl-glucosamine is an essential substance to the middle stage of proteoglycan synthesis. PNA was found within the nucleus and at the cis side of Golgi apparatus, but not in the endoplasmic reticulum nor in the secretion granules. This observation corroborates that beta-D-galactosamine is also essential to the middle stage of proteoglycan synthesis.

Animals↗

Histochemical similarities between human and animal globoid cells in Krabbe's disease: a lectin study.

Lectin-histochemical studies were performed on paraffin-embedded brain tissue sections to identify the specific sugar residues of undegraded "stored" substances in the cytoplasm of globoid cells from patients with globoid cell leukodystrophy. We studied brain tissues from six human patients with galactosylceramide lipidosis (i.e., Krabbe's disease) and compared them to brain tissues from animals with a similar enzyme deficiency including seven Twitcher mice, three dogs and two cats. The globoid cells in all 18 cases studied stained with succinylated-wheat germ agglutinin (S-WGA), but did not stain with Dilichos biflorus agglutinin, soybean agglutinin or Ulex europaeus agglutinin-I. Bandeirea simplicifolia agglutinin-I stained the globoid cells in Twitcher mice, dogs and cats but not those in humans. Concanavalia ensiformis agglutinin, wheat germ agglutinin and Ricinus communis agglutinin-I all stained each of the globoid cells in the mouse, dog and cat tissues, but only in some of the human cases. Peanut agglutinin, however, variably stained globoid cells in the mouse and dog cases but not at all in the human and cat cases. These results demonstrate a common terminal carbohydrate residue N-acetyl glucosamine, which binds S-WGA in the undegraded material stored within the globoid cells in galactoceramide lipidosis. These cells also contained various other stored molecules with sugar residues whose nature is determined by species or individually.

Animals↗

The genome organization of banana bunchy top virus: analysis of six ssDNA components.

We have cloned, sequenced and analysed an additional five circular ssDNA components of banana bunchy top virus (BBTV) which we have called components 2, 3, 4, 5 and 6. These components were present in all BBTV infections tested. Four of these components (components 3, 4, 5 and 6) had one large open reading frame (ORF) in the virion sense located 3' of a stem-loop structure. Each ORF had a potential TATA box and one or two potential polyadenylation signals associated with it and each polyadenylation signal had an associated GC-rich region containing the trinucleotide sequence TTG. A number of ORFs were identified in component 2 but none of these had appropriately located potential TATA boxes and polyadenylation signals associated with them. None of the ORF amino acid sequences nor the full DNA sequences of any of the components had significant sequence identity with any known protein or nucleic acid sequences. However, the ORF of component 4 encoded a 30 residue hydrophobic domain which may indicate that this ORF encoded a transmembrane protein. Further, the ORFs of components 3 and 5 potentially encoded proteins of about 20 kDa, the size of the BBTV coat protein. There were two regions of sequence identity between the five components described here and the previously described component 1. Each component contained a conserved stem-loop structure and a nonanucleotide potential TATA box which was 5' of the large virion-sense ORF in five of the components. The stem-loop structures were incorporated in a common region (CR-SL) of 69 nucleotides which was 62% identical between components. All six BBTV components also contained a major common region (CR-M) which was located 5' of the CR-SL in each component, in the non-coding region and was 76% identical over 92 nucleotides. Each CR-M contained a near-complete 16 nucleotide direct repeat and a GC-box which was similar to the rightward promoter element found in wheat dwarf geminivirus. From these results, BBTV appears to belong to an undescribed plant virus group which could also include subterranean clover stunt virus, coconut foliar decay virus, faba bean necrotic yellows virus and milk vetch dwarf virus.

Amino Acid Sequence↗

Effects of grazing program and subsequent finishing on gene expression in different adipose tissue depots in beef steers.

This experiment was conducted to examine the effects of grazing program and subsequent finishing on gene expression in adipose tissue from steers. Twenty Angus x Angus-Hereford steer calves (initial BW = 231 +/- 25 kg) were allotted randomly to one of two winter grazing treatments: 1) grazing winter wheat pasture to achieve a high rate of BW gain (HGW); or 2) grazing dormant tallgrass native range (NR). Steers in the NR treatment were provided 0.91 kg.steer(-1).d(-1) of a 41% CP (as-fed basis) cottonseed meal supplement. Following the grazing period, steers were assigned randomly to feedlot pens. Steers were fed to a common endpoint of 1.27 cm of backfat between the 12th and 13th rib. Four steers from each treatment were slaughtered at the end of the grazing period, and the remaining steers from each treatment (n = 6) were slaughtered at the predetermined compositional endpoint. Intramuscular and s.c. fat samples were collected from LM sections of each steer at the 12th-/13th-rib interface on the left side. Pools of RNA were prepared for HGW and NR s.c. adipose tissue from steers slaughtered immediately after grazing. Suppression subtractive hybridization was performed followed by dot-blot hybridization screening to confirm differential expression of subtracted transcripts. Transcripts confirmed to be differentially expressed were subjected to dideoxy chain-termination sequencing. Quantitative reverse transcription PCR was performed on three differentially expressed clones: osteonectin, ferritin heavy chain, and decorin. Osteonectin, ferritin heavy chain, and decorin gene expression was greater (P < 0.05) in s.c. than in i.m. adipose tissue of finished steers. A depot x background interaction for osteonectin (P < 0.01) and ferritin heavy chain (P = 0.03) gene expression was observed for steers slaughtered after grazing, indicating that nutritional management can affect gene expression in adipose tissue depots differently. No differences resulting from prefinishing nutritional background (HGW or NR) were noted in osteonectin, ferritin heavy chain, or decorin gene expression in i.m. adipose tissue collected from finished steers, which might have resulted from feeding steers to the same compositional endpoint. Our data suggest that nutritional background alters gene expression in adipose depots, and that depots are influenced differently.

Adipose Tissue↗

Intoxication due to alkylmercury-treated seed--1971-72 outbreak in Iraq: clinical aspects.

Sixty-six hospitalized patients suffering from chronic methylmercury poisoning were examined in Baghdad during 1972. The poisoning was attributed to consumption of home-made bread prepared from seed wheat treated with mercurial fungicide. The age incidence ranged between 4 and 70 years.Of the various clinical features encountered, neurological symptoms and signs were predominant and included muscular weakness, numbness, unsteady gait, paraesthesia, dysarthria, mental disturbances and, in severe cases, blindness, partial deafness, stupor, coma, and death. Involvement of the cardiovascular, urinary, gastrointestinal and haemopoietic systems, which was commonly encountered in ethylmercury poisoning in the 1960 outbreak in Iraq, was unusual.The severity of symptoms and signs was, broadly speaking, dose-dependent; high exposure led to severe clinical manifestations, but variations existed. Criteria, based on the clinical manifestations, were set for grading the severity of cases. The series included 2 asymptomatic cases, 20 mild, 20 moderate, 14 severe, and 10 very severe. In the latter group 5 patients died from failure of the central nervous system.The severely poisoned patients died irrespective of the medical treatment received. After 2 years of observation, most patients graded as mild or moderate cases lost their symptoms completely. Severe cases improved slowly, although ataxia, diminution of visual field and acuity and paraesthesia were still present. Thus, the previously accepted view that neurological signs were irreversible has been disproved.

Adolescent↗

The organization and connections of somatosensory cortex in the brush-tailed possum (Trichosurus vulpecula): evidence for multiple, topographically organized and interconnected representations in an Australian marsupial.

Microelectrode mapping techniques were used to determine the organization of somatosensory cortex in the Australian brush-tailed possum (Trichosurus vulpecula). The results of electrophysiological mapping were combined with data on the cyto- and myeloarchitecture, and patterns of corticocortical connections, using sections cut tangential to the pial surface. We found evidence for three topographically organized representations of the body surface that were coextensive with architectonic subdivisions. A large, discontinuous cutaneous representation in anterior parietal cortex was termed the primary somatosensory area (SI). Lateral to SI we found evidence for two further areas, the second somatosensory area (SII) and the parietal ventral area (PV). While neurones in all of these areas were responsive to cutaneous stimulation, those of SI were non-habituating, whereas those in SII and PV often habituated to the stimuli. Moreover, neuronal receptive fields in SII and PV were, in general, larger than those in SI. Neurones in cortex adjacent to the rostral and caudal boundaries of SI, including cortex that interdigitated between the discontinuous SI head and body representations, required stimulation of deep receptors in the periphery to elicit responses. Within the region of cortex containing neurones responsive to stimulation of deep receptors, body parts were represented in a mediolateral progression. Injections of anatomical tracers placed in electrophysiologically identified locations in SI revealed ipsilateral connections with other parts of SI, as well as cortex rostral to, caudal to, and interdigitating between, SI. Injections in SI also resulted in labelling in PV, SII, motor cortex, posterior parietal cortex and perirhinal cortex. The patterns of contralateral projections reflected those of ipsilateral projections, although they were relatively less dense. The present findings support recent observations in other marsupials in which multiple representations of the body surface were described, and suggest that multiple interconnected sensory representations may be a common feature of cortical organization and function in marsupials.

Animals↗

Parabrachio-cortical connections with the lateral hemisphere in the madagascan hedgehog tenrec: prominent projections to layer 1, weak projections from layer 6.

The present study was undertaken to further characterize and subdivide the rhinal cortex (insular and perirhinal areas) in the hedgehog tenrec (Echinops telfairi), a placental mammal with a rather low encephalisation index. Injections of wheat germ agglutinin-horseradish peroxidase into the dorsolateral pontine tegmentum revealed a prominent layer 1 projection to several rhinal target areas, while the rhinal cortex only stained weakly for the calcitonin gene-related peptide. Among the regions retrogradely labeled following tracer injections into the rhinal cortex, the parabrachial nucleus was considered the main origin of the tegmento-cortical projection. This conclusion was based on the circumscribed pattern of termination, as well as the differences noted between the pattern of anterograde labeling and the pattern obtained by thyrosine hydroxylase immunohistochemistry. The tracer injections into the dorsolateral tegmentum also revealed numerous retrogradely labeled cells in the layer 5 of the dorsomedial frontal cortex. In contrast, the rhinal cortex only showed few labeled cells and most of these cells were located in the layer 6/7. A comparison with other species indicates that the tenrec's parabrachial nucleus gives rise to the most extensive cortical projections but receives the least prominent input from the lateral cerebral hemisphere. The layer 6/7 projection may be a common mammalian feature but it is overshadowed by the layer 5 projection in higher mammals.

Animals↗

Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency.

Patients who have common variable immunodeficiency (CVID) and granulomatous/lymphocytic interstitial lung disease (GLILD) are at high risk for early mortality and B cell lymphomas. Infection with human herpes virus type 8 (HHV8), a B cell lymphotrophic virus, is linked to lymphoproliferative disorders in people who have secondary immunodeficiencies. Therefore, we determined the prevalence of HHV8 infection in CVID patients with GLILD. Genomic DNA isolated from peripheral blood mononuclear cells was screened by nested- and real time-quantitative PCR (QRT-PCR) for the presence of HHV8 genome. It was positive in 6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID-control), and no patients receiving intravenous gamma globulin (n = 13) or normal blood donors (n = 20). Immunohistochemistry (IHC) demonstrated expression of the latency-associated nuclear antigen-1 (LANA-1) in the biopsies of the lung, liver, and bone marrow of four patients with CVID-GLILD. One CVID-GLILD patient developed a B cell lymphoma during the course of the study. QRT-PCR demonstrated high copy number of HHV8 genome and IHC showed diffuse staining for LANA-1 in the malignant lymph node. HHV8 infection may be an important factor in the pathogenesis of the interstitial lung disease and lymphoproliferative disorders in patients with CVID.

Adult↗

Structural variation and evolution of a defense-gene cluster in natural populations of Aegilops tauschii.

Genetic mapping and sequencing of plant genomes have been useful for investigating eukaryotic chromosome structural organization. In many cases, analyses have been limited in the number of representatives sampled from specific groups. The degree of intraspecific genome diversity remains in question. The possibility exists that a single model genome may have limited utility for identifying genes in related members of the species or genus. Crop improvement programs have particular interests in disease resistance genes that are harbored by wild relatives of modern cultivated crops. These genes are evolutionarily dynamic and under selective pressure by a broad range of pathogenic organisms. Using resistance gene analogs as models for gene evolution, intraspecific genome comparisons were made among populations of wild diploid wheat (Aegilops tauschii). We observed that deletion haplotypes are occurring frequently and independently in the genome. Haplotypes are geographically correlated and maintenance of gene complements in localized populations indicates selective advantage. Furthermore, deletion haplotypes are not detrimental to plant health, since genes without adaptive value in alternate environments are eliminated from the genome. Deletion haplotypes appear to be a common form of allelic variation in plants, and we address the consequences on genome restructuring and gene evolution.

Chromosomes, Plant↗

Heterogeneity of avenin, the oat prolamin. Fractionation, molecular weight and amino acid composition.

The prolamin, avenin, was extracted from oat seeds and shown to be maximally extractable in 45% (w/w) ethanol. A purification procedure is described and some properties of avenin are examined. As with wheat and barley prolamins, salt soluble and glutelin fractions were simultaneously extracted. Starch gel electrophoresis revealed two novel fractions, which were isolated by ion-exchange chromatography. These fractions have similar amino acid composition, threonine as the N-terminal amino acid and both have a 22 500 molecular weight. It is suggested that the avenin constituents have a common ancestral gene.

Amino Acids↗

Effect of nitric oxide and plant antioxidants on microsomal content of lipid radicals.

The antioxidant ability of nitric oxide (NO) generated by a chemical donor and of commercially available antioxidant preparations was assayed. SNAP (S-Nitroso-N-acetylpenicilamine) was used as the NO donor, and Ginkgo biloba, wheat and alfalfa preparations were tested. Lipid peroxidation was assayed by EPR employing a reaction system consisting of rat liver microsomes, ADP, FeCl3, NADPH and POBN in phosphate buffer, pH=7.4. In vitro NO exposure decreased microsomal lipid peroxidation in a dose-dependent manner. The dose responsible for inhibiting the microsomal content of lipid radical adducts by 50% (LD50) for SNAP was 550 microM (NO generation rate 0.1 microM/min). The addition of 50 microM hemoglobin to the incubation media prevented NO effect on lipid peroxidation. The addition of an amount of the antioxidant preparations equivalent to the LD50 doses inhibited lipid peroxidation by 21, 15, and 33% for wheat, alfalfa, ginkgo biloba preparations respectively in the presence of 550 microM SNAP. We detected a decrease in the content of lipid radical adducts after simultaneous supplementation, although it was less than 50%, even when LD50 doses of the products were added. This suggests that NO and the natural antioxidants inhibit lipid peroxidation by a mechanism that has both common and non-shared features.

Animals↗