Protective Effect Of Spermine Research Articles

Polyamine metabolism links gut microbiota and testicular dysfunction

BackgroundMale fertility impaired by exogenous toxins is a serious worldwide issue threatening the health of the new-born and causing infertility. However, the metabolic connection between toxic exposures and testicular dysfunction remains unclear.ResultsIn the present study, the metabolic disorder of testicular dysfunction was investigated using triptolide-induced testicular injury in mice. We found that triptolide induced spermine deficiency resulting from disruption of polyamine biosynthesis and uptake in testis, and perturbation of the gut microbiota. Supplementation with exogenous spermine reversed triptolide-induced testicular dysfunction through increasing the expression of genes related to early and late spermatogenic events, as well as increasing the reduced number of offspring. Loss of gut microbiota by antibiotic treatment resulted in depletion of spermine levels in the intestine and potentiation of testicular injury. Testicular dysfunction in triptolide-treated mice was reversed by gut microbial transplantation from untreated mice and supplementation with polyamine-producing Parabacteroides distasonis. The protective effect of spermine during testicular injury was largely dependent on upregulation of heat shock protein 70s (HSP70s) both in vivo and in vitro.ConclusionsThe present study linked alterations in the gut microbiota to testicular dysfunction through disruption of polyamine metabolism. The diversity and dynamics of the gut microbiota may be considered as a therapeutic option to prevent male infertility.1i44qFJDRbDet-fJN3JiqxVideo

Spermine protects from LPS-induced memory deficit via BDNF and TrkB activation.

Lipopolysaccharide (LPS) has been long known to promote neuroinflammation and learning and memory deficits. Since spermine, one of the main natural polyamines in the central nervous system, protects from LPS-induced memory deficit by a mechanism that comprises GluN2B receptors, the aim of the present study was to determine whether brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) receptor and cAMP response element binding (CREB) are involved in this protective effect of spermine. Adult male Swiss albino mice received, immediately after training in the novel object recognition task, saline or LPS (250 μg/kg, i.p.); 5 min later they received saline or spermine (0.3 mg/kg, i.p.) and, when specified, 5 min thereafter saline or the TrkB receptor antagonist ANA-12 (0.5 mg/kg, i.p.) in different flanks. Animals were tested 24 h after training. Spermine protected from LPS-induced memory deficit and this protective effect was reversed by ANA-12. In a subset of animals BDNF, CREB and phospho-CREB immunoreactivity was determined in the hippocampi and cerebral cortex 4 h after spermine injection. Spermine reversed the decrease of mature BDNF levels induced by LPS in both hippocampus and cerebral cortex. Spermine increased phospho-CREB content and phospho-CREB/total CREB ratio in the cerebral cortex of LPS-treated mice. The results support that the protective effect of spermine on LPS-induced memory deficits depends on TrkB receptor activation and is accompanied by restoration of mature BDNF levels in hippocampus and cerebral cortex, as well as increased CREB phosphorylation in the cerebral cortex.

Protective effect of spermine against pentylenetetrazole kindling epilepsy induced comorbidities in mice

Nitric oxide (NO), an important intracellular signaling molecule is involved in modulation of neuronal transmission. The NO level increases during epileptic activity in animal models of epilepsy. However, its role in epileptic activity remains controversial. Spermine is an endogenous polyamine; possesses anti-oxidant property and has ability to modulate ion channels and NO synthase activity. Therefore, the present study was designed to investigate the role of NO pathway in the neuroprotective effect of spermine, in Pentylenetetrazol (PTZ) induced kindling epilepsy in mice. PTZ (35mg/kg; intraperitoneal, i.p.) was administered on every alternate day up to 29days and challenge test was performed on 33rd day. From 15th day, spermine (5 and 10mg/kg; i.p.), L-NAME (10mg/kg; i.p), l-Arginine (50mg/kg; i.p) and sodium valproate (400mg/kg; i.p.) were administered up to 33rd day. Animals were sacrificed on 34th day for estimation of biochemical and neurotransmitters. Pretreatment with spermine, considerably, reversed the PTZ induced alterations. Further, pretreatment of L-NAME and l-Arginine with 5 and 10mg/kg; i.p. spermine, respectively, leads to an increase and decrease in its protective effects. The present study suggests the involvement of NO pathway in the protective effect of spermine against PTZ-induced kindling epilepsy in mice.

Oxidative stress and some antioxidant systems in acid rain-treated bean plants: Protective role of exogenous polyamines

The effect of simulated acid rain (AR) (pH 1.8) on H 2O 2 and malonyldialdehyde (MDA) levels and activities of peroxidase and catalase in bean plants were investigated. The influence of exogenous polyamines spermidine and spermine on these parameters was also studied. AR treatment induced lipid peroxidation and increased level of H 2O 2 in leaves. Pretreatment with spermidine and spermine prevented these changes. The protective effect of spermine was higher than that of spermidine. The impact of polyamines could be attributed to their acid neutralizing and antioxidant effects, as well as to their ability to stabilize membranes by associating with negatively charged phospholipids. It was also found that AR significantly increased peroxidase and decreased catalase activities at the first hours after treatment. Later, both enzyme activities were enhanced that could contribute to the scavenging and detoxification of active oxygen species.

Subcellular aspects of the protective effect of spermine against atrazine in pea plants

The action of the exogenously applied tetraamine spermine in reversing the effect of atrazine stress on intact pea plants (Pisum sativum L., cv. Koray) was investigated at the ultrastructural level. The results indicate that atrazine increases cell senescence by lipid peroxidation and loss of unsaturated fatty acids from thylakoid membranes of pea plant chloroplasts. Spermine acts as a polyfunctional effector. It stabilises the molecular composition of the membranes by preventing lipid peroxidation and as a consequence protects the conformation of the thylakoid system and structural integrity of the chloroplasts. Spermine treatment also contributes to the process of neutralisation of the free radicals by peroxisomes.

Spermine protects in vivo the antioxidant enzymes in transiently hypoperfused rat brain.

The antioxidant enzymatic system in brain hypoperfusion/reperfusion model in rats after spermine administration was evaluated. Incomplete cerebral ischemia/reperfusion induced by temporal occlusion of common carotid arteries caused a decrease in the activities of superoxide dismutase and glutathione reductase as well as total and free sulfhydryl groups, while thiobarbituric acid-reactive substances became elevated. Administration of spermine after the reperfusion led to restoring all above parameters to normal values. Protective effect of spermine in transiently hypoperfused and subsequently reperfused rat brain is briefly discussed.

Polyamine concentration in rat milk and food, human milk, and infant formulas.

The polyamine concentration in rat milk and food, human milk, and infant formulas was estimated by HPLC. In rat milk, the concentration of putrescine and spermine was low (generally under 2.5 nmol.mL-1 for putrescine and under 1 nmol.mL-1 for spermine). The spermidine concentration was higher and seemed to increase during lactation. The rat food was richer in polyamines than the rat milk (about 150 times for putrescine and spermine, about 30 times for spermidine). We already proved that ingestion of spermine or spermidine can induce precocious maturation of the rat intestine. The present observations suggest that polyamines contained in rat food could play an important role in postnatal maturation of the rat intestine. The polyamine concentration of human milk was measured from 60 different mothers during a period extending from the 1st wk to the 6th mo of lactation. Great variation was observed. During the 1st mo of lactation, the general pattern was as follows: putrescine concentration generally varied little (from 1 to 3 nmol.mL-1), spermine and spermidine concentrations showed a similar pattern (the highest values appeared at the end of the 1st wk of suckling). After the 4th mo of lactation, putrescine concentration increased slightly, whereas spermine and spermidine concentration stayed almost stable. The concentrations of polyamines in 18 powdered milks for babies were estimated. Spermine and spermidine contents were lower than those in human milk. A protective effect of spermine or spermidine against alimentary allergies is suggested.

Spermine prevents endonuclease activation and apoptosis in thymocytes

Glucocorticoid hormones, Ca 2+ ionophores, and some toxic chemicals activate a suicide process in thymocytes, known as apoptosis or programmed cell death. A crucial event in apoptosis is the activation of a Ca 2+- and Mg 2+-dependent endonuclease that promotes extensive DNA fragmentation. In this study, we investigated the effect of various polyamines on endonuclease activation leading to thymocyte apoptosis. We found that both glucocorticoid- and Ca 2+ ionophore-induced DNA fragmentation and apoptosis were prevented by spermine. Other polyamines such as putrescine or spermidine had moderate or no effect. Moreover, spermine, and to a lesser extent spermidine, but not putrescine, prevented endonuclease activation in permeabilized liver nuclei incubated in the presence of Ca 2+ and Mg 2+, indicating that spermine efficiency in blocking DNA fragmentation was related to the interaction of this polyamine with the endonuclease or its substrate, DNA. Experiments with the fluorescent dye, ethidium bromide, and a purified preparation of liver endonuclease revealed that the protective effect of spermine on DNA fragmentation was related to its ability to modify the chromatin arrangement. Thymocytes incubated with methyl glyoxal bis(guanylhydrazone) to deplete intracellular spermine exhibited spontaneous DNA fragmentation, which suggests that modulation of the intracellular polyamine content and regulation of chromatin structure may play a critical role in the early phases of apoptosis. Finally, these results demonstrate that inhibition of DNA fragmentation also prevents the onset of apoptosis, directly linking endonuclease activation and cell death.

The protective effect of spermine and other polyamines against heat denaturation of deoxyribonucleic acid.

The protective effect of spermine and other polyamines against heat denaturation of deoxyribonucleic acid.