Doses Of Spermine Research Articles

Effects of Spermine and Spermidine supplemented extenders on post-thaw Spermatological Parameters in Stallion Semen Cryopreservation

In this study, the effects of polyamines, Spermine and Spermidine, on long-term preservation and post-thaw spermatological parameters were evaluated. Moreover, determination of the most suitable polyamine and its dose that can be added to standard extenders were aimed. Four adult Arabian stallions were used in the study. Five ejaculates were collected from each of four stallions via artificial vagina two days interval. Each ejaculate was divided into 13 aliquots. INRA96 (95,5%), egg yolk (2%), and glycerol (2,5%) were used as a control extender. Extenders of experimental groups were prepared with different doses of Spermine and Spermidine (0,1 mg/ml; 0,2 mg/ml; 0,4 mg/ml; 1 mg/ml; 2 mg/ml; 4 mg/ml). Stallion semen that were cryopreserved with Control and experimental extenders were evaluated in terms of Total Motility, Progressive Motility, Plasma Membrane Integrity, Capacitation Index, Acrosome Integrity and DNA Fragmentation Index. At the end of the evaluations, it was determined that 0,2 mg/ml Spermine and 0,4 mg/ml Spermidine showed better Total Motility and Progressive Motility, numerically. On the other hand, it was observed that 4 mg/ml Spermine and Spermidine had the lowest statistically significant values (p < 0,001). While statistically similar differences were obtained between groups in terms of the Plasma Membrane and Acrosome Integrity, it was determined that all experimental groups had lower and statistically significant values in terms of Capacitation and DNA Fragmentation Index (p < 0,001). As result, it was observed that the stallion semen cryopreservation success can be increased by the addition of 1–2 mg/ml Spermine that had effective protection on Capacitation and DNA Fragmentation Index without damaging other spermatological properties.

Effects of spermine supplementation on the morphology, digestive enzyme activities, and antioxidant capacity of intestine in weaning rats.

The main objective of this study was to investigate the effects of different doses of spermine and its extended supplementation on the morphology, digestive enzyme activities, and intestinal antioxidant capacity in weaning rats. Nineteen-day-old male rats received intragastric spermine at doses of 0.2 and 0.4 μmol/g BW for 3 or 7 d, whereas control rats received similar doses of saline. The results are as follows: 1) In the jejunum, the seven-day supplementation with both doses of spermine significantly increased crypt depth (P < 0.05) compared with the control group; the supplementation extension of the high spermine dose increased villus height and crypt depth (P < 0.05); in the ileum, the low spermine dose significantly increased villus height and crypt depth compared with the control group for 7 days (P < 0.05). 2) The 3-day supplementation with high spermine dose increased alkaline phosphatase activity in the jejunum (P < 0.05). 3) In the jejunum, the anti-hydroxyl radical (AHR), total superoxide dismutase (T-SOD), catalase (CAT), and total antioxidant capacity (T-AOC) activities were increased (P < 0.05); however, the malondialdehyde (MDA) content was reduced (P < 0.05) in groups supplemented with the high spermine dose relative to those in the control groups after 3 and 7 d; moreover, the anti-superoxide anion (ASA) and glutathione (GSH) contents increased with the high spermine dose that lasted for 3 days (P < 0.05). Furthermore, the T-SOD and CAT activities (after 3 and 7 d), ASA (after 3 d), and AHR (after 7 d) increased with the high spermine dose compared with those of the low spermine dose (P < 0.05). Extending the supplementation duration (7 d) of the high spermine dose decreased the MDA content and ASA and T-AOC activities (P < 0.05). These results suggested that spermine supplementation can modulate gut development and enhance the antioxidant status of the jejunum in weaning rats, and a dosage of 0.4 μmol spermine/g BW had better effects than the dosage of 0.2 μmol spermine/g BW on accelerating gut development and increasing antioxidant capacity.

THE EFFECTS OF SPERMINE ON NEUROGENESIS AND THE PASSIVE AVOIDANCE LEARNING AFTER TRANSIENT CEREBRAL ISCHEMIA IN THE CHICKS

Event Abstract Back to Event THE EFFECTS OF SPERMINE ON NEUROGENESIS AND THE PASSIVE AVOIDANCE LEARNING AFTER TRANSIENT CEREBRAL ISCHEMIA IN THE CHICKS Ebru Ayrancı1 and Suleyman Kaplan1* 1 Ondokuz Mayis University, Turkey Süleyman Kaplan1, M. Emin Önger1, Ebru Ayrancı1, G. Ömür Deniz1, Mehtap Güney1, M. Önder Karayiğit2, Zuhal Altunkaynak1, Murat Yarım2, Cafer Marangoz3 1Department of Histology-Embryology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey 2Department of Pathology, Veterinary Faculty, Ondokuz Mayıs University, Samsun, Turkey 3Department of Physiology, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey ABSTRACT Objective: The aim of this study is to investigate the effects of spermine on neurogenesis and the passive avoidance learning following transient cerebral ischemia in the chicks. The neuroprotective effect of spermine in hippocampus is searched morphologically and functionally. Materials and Methods: The study was composed of three groups of chicks: pure controls (n=20), sham group (n=20) and ischemia groups (n=40). Passive avoidance was thought to 10 chicks respectively in the control and PA(+) sham group. The other 10 chicks of this group were not thought passive avoidance PA(-). Twenty chicks in the experiment group were PA(+), other 20 chicks were PA(-). The ischemia group was received a 20 minute ischemia. The ischemia and spermine group 30 minutes before the ischemia, intraperitoneally 10 mg/kg/day spermine were received. After seven days of the ischemia, all animals were retested for recalling and than were sacrificed. The brains were fixed with buffered formalin. The series of brain sections were stained with crystal violet. After staining, total numbers of neurons were estimated stereologically in Cyresl violet stained sections. Results: The number of probably newly developed neurons and total neurons were estimated using stereological techniques. There were found significant differences between the control PA(+) and the ischemia PA(-) groups (p<0.05); the control PA(+) and the ischemia+spermine PA(+) groups (p<0.01); the sham PA(+) and the ischemia+spermine PA(+) groups (p<0.05); the sham PA(-) and ischemia+spermine PA(-) groups (p<0.05); ischemia PA(+) and ischemia+spermine PA(+ ) (p<0.05). Conclusion: In this study we investigated the effects of spermine on neurogenesis and the passive avoidance learning following transient cerebral ischemia in the chicks. The neuroprotective effect of spermine in hippocampus was observed morphologically with cell counting technique and functionally with passive avoidance evaluation. The dose of spermine used in this study has a neuroprotective effect on the hippocampus after transient cerebral ischemia. Keywords: Ischemia, Spermine, Learning, Stereology, chick. Conference: 4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Turkey, 30 Sep - 3 Oct, 2012. Presentation Type: Poster Presentation Topic: Abstracts Citation: Ayrancı E and Kaplan S (2013). THE EFFECTS OF SPERMINE ON NEUROGENESIS AND THE PASSIVE AVOIDANCE LEARNING AFTER TRANSIENT CEREBRAL ISCHEMIA IN THE CHICKS. Conference Abstract: 4th Conference of the Mediterrarnean Neuroscience Society. doi: 10.3389/conf.fnhum.2013.210.00005 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jan 2013; Published Online: 11 Apr 2013. * Correspondence: Prof. Suleyman Kaplan, Ondokuz Mayis University, Samsun, Turkey, skaplanomu@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ebru Ayrancı Suleyman Kaplan Google Ebru Ayrancı Suleyman Kaplan Google Scholar Ebru Ayrancı Suleyman Kaplan PubMed Ebru Ayrancı Suleyman Kaplan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effect of postharvest treatments with polyamines on physiological and biochemical attributes of kiwifruit (Actinidia deliciosa) cv. Allison

Introduction . Kiwifruit is a typical climacteric fruit, which grows profitably well in sub-temperate climatic conditions. The major problem with kiwifruit is that it does not ripen for about a week at room temperature but after this period there is a sudden rise in the respiration rate and fruits remain in edible condition for only a few days, giving it a very short shelf life in ambient conditions. Materials and methods . Kiwifruits were treated with different concentrations of spermine [(0.5, 1.0 and 1.5) mM] and spermidine [(1.0, 1.5 and 2.0) mM] by the immersion method; biochemical and physiological analyses were carried out, then fruit were stored in ambient conditions for 15 days. Results and discussion . Polyamine-treated fruits did not show any amount of ethylene evolution up to the 6th day of storage as compared with those of control, in which it started after the 3rd day of storage. The respiration rate was also the lowest in treated fruit. Similarly, polygalacturonase and lipoxygenase activities rose rapidly in control fruits in comparison with polyamine-treated fruits. Conclusion . The doses of spermine at 1.5 mM and spermidine at 2.0 mM showed the best results in extending the shelf life of kiwifruits when stored in ambient conditions [(22 ± 4) ◦ C, RH: (65 ± 5)%].

Oral administration of spermine advances intestinal maturation in sucking piglets

AbstractThe objective of this study was to investigate the effect of orally administered spermine at various doses on intestinal maturation in sucking piglets. Thirty-six 11-day-old sucking piglets were assigned randomly to one of six treatments to receive via a stomach tube 0, 0·1, 0·2, 0·3, 0·4, or 0·5 mmol spermine per kg live weight (LW) per day for 3 days. At day 14 of age, duodenum, jejunum and ileum were obtained for biochemical and morphological analysis. Increasing the dose of orally administered spermine increased intestinal weight (linear effect, P&lt;0·01), mucosal weight (linear effect, P&lt;0·05), and mucosal protein, DNA and RNA contents of the duodenum (linear effect, P≤0·01) and jejunum (linear effect, P&lt;0·01). Elevating spermine doses also enhanced (linear effect, P≤0·02) the specific activities of maltase and sucrase but decreased (linear effect, P&lt;0·01) lactase specific activity in the jejunum and duodenum. Furthermore, augmenting oral doses of spermine increased crypt depth and villus width but reduced villus height in the jejunum (linear effect, P&lt;0·05) and duodenum (linear effect, P&lt;0·01). For most measurements, the effects were observed at the oral spermine doses of 0·3 to 0·5 mmol/kg LW per day. Collectively, the results show that oral administration of optimal doses of spermine to 11-day-old sucking piglets induces precocious intestinal maturation and promotes intestinal growth.

Effect of L-type calcium channel antagonists on spermine-induced CNS excitation in vivo

The ability of nitrendipine, nisoldipine, verapamil and gabapentin to inhibit the development of CNS excitation induced by spermine was assessed in mice. Injection of an excitotoxic dose of spermine (100 μg, i.c.v.) in mice results in worsening tremor that culminates in the development of a fatal tonic convulsion within 8 h of spermine administration. The dihydropyridines, nitrendipine and nisoldipine, which are L-type calcium channel antagonists acting at the α1 subunit, inhibited the development of spermine-induced effects. Verapamil, which also acts at the α1 subunit of the L-type calcium channel, also inhibited the development of spermine-induced CNS excitation. Gabapentin, a postulated L-type calcium channel antagonist interacting at the α2δ subunit, did not inhibit the development of spermine-induced effects. These results show that antagonists of the α1 subunit of L-type calcium channels can effectively inhibit the effects of spermine in vivo. This may highlight the importance of L-type calcium channels in spermine action.

The Effect of e-, i-, and n-Nitric Oxide Synthase Inhibition on Colonic Motility in Normal and Muscular Dystrophy (Mdx) Mice

To explore the origin of diarrhea or constipation in human Duchenne muscular dystrophy (DMD), the effect of the inhibition of e- , i-, and n-nitric oxide synthase (NOS) on the motility of proximal and distal segments of colon of muscular dystrophy (mdx) and control mice was studied. The frequency of migrating motor complexes (MMC) was higher in the proximal than in the distal segments in mdx colon (0.56 vs. 0.25 cpm) and in the control colon (0.7 vs. 0.25 cpm), and there was no difference when mdx was compared to control segments. High concentrations of NOS inhibitors, including 1,3-PBIT dihydrobromide (1,3-PBIT) and spermine, inhibited MMC. The dose of spermine required to inhibit MMC was lower for the proximal mdx colon than for the distal mdx or control colon. In the presence of tetrodotoxin, spermine (1 mM) and 1,3-PBIT (5 mM) reduced the magnitude of local, rhythmic contractions (LC) paced by the interstitial cells of Cajal (ICC), but 1,3-PBIT (50 microM) increased their magnitude. There was no difference in the effect of spermine and 1,3-PBIT on the LC between mdx and control colon. The results suggest an inhibition of MMC by high concentrations of e-, i-, and n-NOS inhibitors, modulation of ICC activity by e-NOS, and greater susceptibility of MMC to n-NOS inhibition in the mdx proximal than in the control colon, which is very likely because of a deficit in n-NOS in the mdx smooth muscle affecting the MMC pacemaker. A deficit in the effect of mdx smooth muscle n-NOS on an MMC pacemaker may be the origin of diarrhea or constipation in human DMD.

Intrathecal spermine and spermidine at high-doses induce antinociceptive effects in the mouse capsaicin test

The antinociceptive effects of intrathecally (i.t.) administered high doses of spermine and spermidine, endogenous polyamines, were examined in the mouse capsaicin test. Spermine (2.5-10 nmol) and spermidine (10 and 15 nmol), when administered i.t. 5 min before the injection of capsaicin solution (1600 ng) into the plantar surface of a hindpaw, produced a significant reduction of the nociceptive behavioral response. Ifenprodil (2 and 4 nmol), an antagonist of the polyamine recognition site on N-methyl-D-aspartate (NMDA) receptor ion-channel complex, co-administered with spermine or spermidine significantly inhibited antinociception induced by both polyamines. These results indicate that spermine- and spermidine-induced antinociception may be mediated via the polyamine recognition site on NMDA receptor ion-channel complex in the mouse spinal cord.

Brain lesions and delayed water maze learning deficits after intracerebroventricular spermine

The effects of spermine on the acquisition and retention of spatial learning in the Morris water maze were studied. Spermine 25 and 125 nmol i.c.v. did not alter the ability of rats to find a hidden platform in the water maze when administered before training over 5 days. However, the inhibitory effect of the benzodiazepine, diazepam (3 mg/kg i.p., 30 min prior to training), on path length to target was markedly potentiated by the higher dose of spermine, consistent with spermine acting as a functional antagonist at the NMDA receptor. This drug combination did not affect performance on visible platform trials. Administration of doses of 125 and 250 nmol (but not 62.5 nmol) of spermine i.c.v. in the week prior to training (daily for 5 days) dose-dependently inhibited subsequent learning of a platform position in the absence of drug. These higher doses of spermine produced neuronal loss and increased [ 3 H] PK11195 binding indicating microglial activation predominantly in the hippocampus and to a lesser extent in the striatum, septum, thalamus and amygdala. Spermine 125 nmol i.c.v. (daily for 7 days) also abolished retention of a previously learned platform position when administered in an interval between training and retention testing. The inhibitory effects of spermine 125 nmol i.c.v. (daily for 7 days) on subsequent spatial learning were not antagonised by concomitant administration of 30 nmol dizocilpine. These results demonstrate that spermine produces a delayed neurotoxic effect in particular neuronal populations in the brain that selectively impair spatial learning and recall.

Investigation of the actions and antagonist activity of some polyamine analogues in vivo.

1. The ability of three putative polyamine antagonists to antagonize behavioural changes induced by spermine was assessed. 2. Injection of an excitotoxic dose of spermine (100 microg, i.c.v.) in mice results in the development of a characteristic behavioural profile, which has two temporally distinct phases. The early events include clonic convulsions, and the later, more general excitation, includes tremor and culminates in the development of a fatal tonic convulsion. 3. Co-administration of arcaine (25 microg, i.c.v.) potentiated the early phase effects after spermine injection, but antagonized the development of spermine-induced tonic convulsions. A larger dose of arcaine (50 microg, i.c.v.) given alone resulted in the development of spermine-like body tremor and convulsions. It therefore appears that arcaine is not a pure polyamine antagonist in vivo, but may be a partial agonist. 4. Similarly, 1,10-diaminodecane appeared to act as a partial agonist in vivo, although it was less potent than arcaine. 5. In contrast, diethylenetriamine (DET) effectively inhibited the development of the early effects of spermine, but was ineffective against the spermine-induced CNS excitation and tonic convulsions. 6. It is concluded that none of the putative polyamine antagonists tested behaved as effective polyamine antagonists in vivo, although each produced some antagonism.

Effects of a single dose of orally-administered spermine on the intestinal development of unweaned rats.

Investigations were undertaken to obtain information on the mechanism by which orally administered spermine induces postnatal maturation in the rat intestine. Suckling rats ingested one dose of spermine (8 mumol) then were sacrificed at different intervals. -A. Proximal and distal parts of the intestine were homogenised. -B. A modification of the Wieser's technique was used to isolate cell fractions from the proximal mucosa. Wet weight and length of intestine; protein content, DNA amount, disaccharidase activity, polyamine amounts in intestinal and cellular extracts were measured. Spermine ingestion induced two phases of events: first, a cellular desquamation then a new cell differentiation. In the isolated epithelial cells, two and four hours after spermine ingestion, modifications in lactase and maltase specific activity were recorded, as were variations in spermine, spermidine and putrescine content. These observations clarify the cellular and molecular events of the intestinal development occurring after spermine ingestion and open new research perspectives.

N-methyl- d-aspartate receptor-mediated changes in thermal nociception: Allosteric modulation at glycine and polyamine recognition sites

The effects of allosteric modulators of the N-methyl- d-aspartic acid receptor ion-channel complex on the nociceptive tail-flick reflex were studied in awake rats. Intrathecal administration of d-serine (100 fmol−1 μmol) but not l-serine or glycine to the lumbar spinal cord produced a facilitation of the tail-flick reflex at doses ⩾ 1 pmol (maximum at 0.5−1 min). Intrathecal pretreatment with the glycine modulatory site antagonist 7-chlorokynurenic acid (3 pmol) blocked both d-serine-produced and N-methyl- d-aspartate-produced facilitation of the tail-flick reflex. d-serine-produced facilitation was also blocked by intrathecal pretreatment with a N-methyl- d-aspartate receptor ion-channel blocker, MK 801 (100 fmol), or with an alternate substrate for nitric oxide synthase, N G-nitro- l-arginine-methyl ester (100 nmol). Intrathecal administration of spermine (0.01 nmol−3 μmol) produced biphasic effects on tail-flick latency accompanied by mechanical hyperesthesia and vocalization at greater doses. Spermine-produced facilitation (maximum with 0.01 nmol to 1 nmol at 1 min) was blocked by intrathecal pretreatment with MK 801 (100 fmol), N G-nitro- l-arginine-methyl ester (100 nmol) or the polyamine modulatory site antagonist, arcaine (10 nmol). Spermine-produced inhibition (maximum with 300 nmol at 2 min) was blocked by intrathecal administration of MK 801 (1 nmol). Intrathecal administration of the N-methyl- d-aspartate receptor antagonist, d-2-amino-5-phosphonopentanoic acid (1 nmol), blocked inhibition and uncovered a facilitation produced by 1 μmol spermine. In addition, spermine produced multi-stage motor effects (immediate- and late-onset). Intrathecal pretreatment with MK 801 (1 nmol) blocked only the immediate-onset motor effects while the late-onset motor effects were selectively blocked by pretreatment with the kappa opioid receptor antagonist, nor-binaltorphamine (200 nmol). Taken together, these data suggest that d-serine and spermine facilitate nociceptive transmission by positive allosteric modulation of the N-methyl- d-aspartate receptor ion-channel. Furthermore, activation of the N-methyl- d-aspartate receptor is also necessary to elicit the immediate-onset motor effects and inhibition of the tail-flick reflex produced by greater doses of spermine. Because kappa opioid receptors appear to be involved, the spermine-produced late-onset motor effects may involve endogenous dynorphin release.

Spermine decreases peripheral vascular resistance in the dog and relaxes the isolated aorta of the guinea pig.

Polyamines, found in all nucleated cells, have been shown to relax uterine, gastrointestinal, and respiratory tract smooth muscle. When parenterally administered to the rat or dog they cause hypotension. To determine the range of the relaxing effect of polyamines on smooth muscle and the mechanism of the hypotensive effect anaesthetised dogs were infused with increasing intravenous bolus doses of spermine while cardiovascular measurements were made. At doses of greater than or equal to 2 mg X kg-1 spermine a reversible hypotensive effect was produced that is accounted for by changes in peripheral vascular resistance. It is unlikely that this effect was due to the known propensity of polyamines to release histamine because the hypotensive action of 2 mg X kg-1 spermine was unaltered by pretreatment with the H1 and H2 blockers, diphenhydramine and cimetidine. Evidence that the spermine effect is not mediated by circulating agents was shown by the ability of spermine to relax the precontracted guinea pig isolated aorta. These results in vascular smooth muscle may be added to those in other types of smooth muscle shown to be relaxed by polyamines; the polyamine effect on smooth muscle may be ubiquitous. These data also raise the possibility that changing concentrations of tissue polyamines may play a role in the regulation of tissue blood flow.

Induction of spermidine/spermine N1-acetyltransferase in rat tissues by polyamines.

Treatment of rats with spermidine, spermine or sym-norspermidine led to a substantial induction of spermidine/spermine N1-acetyltransferase activity in liver, kidney and lung. The increase in this enzyme, which was determined independently of other acetylases by using a specific antiserum, accounted for all of the increased acetylase activity in extracts from rats treated with these polyamines. Spermine was the most active inducer, and the greatest effect was seen in liver. Liver spermidine/spermine N1-acetyltransferase activity was increased about 300-fold within 6 h of treatment with 0.3 mmol/kg doses of spermine; activity in kidney increased 30-fold and activity in the lung 15-fold under these conditions. The increased spermidine/spermine N1-acetyltransferase activity led to a large increase in the liver putrescine content and a decline in spermidine. These changes are due to the oxidation by polyamine oxidase of the N1-acetylspermidine formed by the acetyltransferase. Our results indicated that spermidine was the preferred substrate in vivo of the acetylase/oxidase pathway for the conversion of the higher polyamines into putrescine. The induction of the spermidine/spermine N1-acetyltransferase by polyamines may provide a mechanism by which excess polyamines can be removed.

Inhibition of platelet aggregation and endogenous lectin activity by oligoamines

Amino sugars and basic amino acids inhibit platelet aggregation and the activity of the endogenous platelet lectin, yet,relatively high concentrations(∼ 30 mM) are required for the inhibition. If cooperative interactions are involved in these platelet surface activities, oligomers of primary amines should be more potent inhibitors than their individual component amines. Accordingly, series of oligomers of basic amino acids,of the polyamines (putrescine, spermidine and spermine) and of aliphatic diamines differing in chain length were tested for potency of inhibition of platelet aggregation and endogenous platelet lectin activity. Indeed,oligoamines were much more potent inhibitors of platelet aggregation than their corresponding monomers or shorter oligomers, more than accountable by an additive effect. For example, 60, 3 and 0.3 mM were needed for 50% inhibition of platelet aggregation by lysine, (lys) 3 and (lys) 5, respectively. A similar pattern was observed for the effect of the oligoamines on the activity of the endogenous platelet lectin. The inhibition of platelet aggregation by spermine is competitive, since the effect of a given dose of spermine decreased with increasing platelet concentration. Neither inhibition of platelet-inducer interaction nor Ca 2+ insufficiency explain the inhibitory effects of the oligoamines.

Oral administration of spermine inhibits gastric acid secretion in rats.

Administration of spermine by oral route inhibits the histamine-stimulated gastric acid secretion in pylorous ligated rats. The extent of both the acid and volume of secretion is dependent on the dose of spermine. The polyamine is completely ineffective when injected by the intravenous route. A single oral dose of spermine suppresses acid secretion for at least 6 hr. An inverse relationship between the efficacy of oral spermine and age of the animals was observed. These data suggest a therapeutic potential for the naturally occurring polyamine compounds.