Spermine functions as a direct free radical scavenger, particularly against hydroxyl radicals (•OH) generated in a Cu(II)/H₂O₂ system.

ROS-induced DNA damage is inhibited by spermine (NSC 268508) at physiologically relevant doses; peak suppression is shown at 1 to 2 mM. These concentrations fall comfortably within the range of physiological spermine concentrations that have been estimated [1].

---

Spermine at physiologically relevant concentrations (1-2 mM) effectively inhibited reactive oxygen species (ROS)-induced DNA strand breaks in a ΦX-174 plasmid DNA system containing 30 µM H₂O₂ and 10 µM CuCl₂. The protection was concentration-dependent, with significant inhibition observed starting at 0.1 mM.
In an Electron Paramagnetic Resonance (EPR) assay using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap in the same Cu(II)/H₂O₂ system, 1 mM spermine inhibited the formation of the DMPO-OH adduct by >70%. The inhibition of the DMPO-OH signal was observed at concentrations as low as 0.1 mM spermine.
Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) analyses using synthetically prepared bis-α-[¹³C]spermine confirmed direct interaction with hydroxyl radicals. In the presence of the ROS-generating system, the original ¹³C-NMR peak of labeled spermine disappeared, and new peaks appeared, indicating the formation of adducts. Chemical Ionization Mass Spectrometry identified potential adduct fragments, supporting a mechanism where spermine is oxidized, leading to products such as a dialdehyde.

Metabolism / Metabolites
Uremic toxins often accumulate in the blood due to overeating or poor kidney filtration. Most uremic toxins are metabolic waste products that are normally excreted through urine or feces.

Toxicity Summary
Uremic toxins, such as spermidine, can be actively transported to the kidneys via organic ion transporters, particularly OAT3. Elevated levels of uremic toxins can stimulate the production of reactive oxygen species (ROS). This appears to be mediated by the direct binding of uremic toxins to or inhibition of NADPH oxidases, particularly NOX4, which is abundant in the kidneys and heart (A7868). ROS can induce a variety of different DNA methyltransferases (DNMTs) involved in the silencing of a protein called KLOTHO. KLOTHO has been shown to play important roles in anti-aging, mineral metabolism, and vitamin D metabolism. Multiple studies have shown that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney disease due to elevated local ROS levels (A7869). Speridine is produced by spermidine synthase. Speridine is a polyamine, a small organic cation essential for eukaryotic cell growth. Speridine is typically present in the cell nucleus at millimolecular concentrations. Spermine acts directly as a free radical scavenger and forms various adducts to prevent DNA oxidative damage. Oxidative damage to DNA from reactive oxygen species is a persistent problem that cells must guard against for survival. Therefore, spermine is an important natural intracellular compound that can protect DNA from free radical attack. Spermine also participates in gene expression regulation, chromatin stabilization, and prevention of endonuclease-mediated DNA fragmentation. High concentrations of oxidized polyamines (such as spermidine dialdehyde) can be toxic. However, this study shows that once spermine is oxidized during free radical scavenging, its affinity for DNA decreases, allowing it to diffuse and be detoxified through cellular mechanisms (such as reaction with glutathione). Therefore, under the proposed conditions, this mechanism is unlikely to produce significant toxicity.

[1]. The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11140-5.

[2]. Polyamines and Their Role in Virus Infection. Microbiol Mol Biol Rev. 2017 Sep 13;81(4). pii: e00029-17.

Spermine is a polyazine belonging to the tetradecane family, with its carbon atoms at positions 1, 5, 10, and 14 replaced by nitrogen atoms. Spermine plays a wide range of roles in cellular metabolism, acting as an antioxidant, immunosuppressant, and important metabolite. It is a polyazine and tetraamine, the conjugate base of spermine(4+). Spermine is a biogenic polyamine derived from spermine, existing as a polycation at all pH values. It is present in a variety of tissues and organisms, often functioning as an important growth factor in certain bacteria. Spermine is associated with nucleic acids, particularly viruses, and is thought to stabilize their helical structures. Spermine is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). Spermine has also been reported in Cyanidium caldarium, Brasenia schreberi, and other organisms with relevant data. Spermine is a polyamine with a structure similar to tetradecane, but with nitrogen atoms replacing the carbon atoms at positions 1, 5, 10, and 14. Spermine plays a wide range of roles in cellular metabolism. Spermine is a uremic toxin. Based on chemical and physical properties, uremic toxins can be classified into three main categories: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small molecule, lipid-soluble compounds and/or protein-bound compounds, such as phenols; 3) larger so-called medium molecules, such as β2-microglobulins. Long-term exposure to uremic toxins can lead to a variety of diseases, including kidney damage, chronic kidney disease, and cardiovascular disease. Spermine is associated with nucleic acids, especially in viruses, and is thought to stabilize their helical structures. [PubChem] Spermine is a metabolite found or produced in Saccharomyces cerevisiae. It is a biogenic polyamine formed from spermine. It is present in a variety of organisms and tissues and is an essential growth factor for some bacteria. It exists as a polycation at all pH values. Spermine is associated with nucleic acids, especially in viruses, and is believed to stabilize their helical structure.
See also: hydrocarbons, terpene processing byproducts (note moved to).
Pharmacological Indications
For nutritional supplementation, and also for treating dietary deficiencies or imbalances.
Mechanism of Action
Spermine is produced by spermine synthase. Spermine is a polyamine, a small organic cation, essential for eukaryotic cell growth. Spermine is typically present in the cell nucleus at millimolecular concentrations. Spermine acts directly as a free radical scavenger and forms various adducts to prevent DNA oxidative damage. Oxidative damage to DNA from reactive oxygen species is a persistent problem that cells must defend against for survival. Therefore, spermine is an important natural intracellular compound that protects DNA from free radical attack. Spermine also participates in gene expression regulation, chromatin stabilization, and prevention of endonuclease-mediated DNA fragmentation.
Pharmacodynamics
Spermine is a polyamine, an organic molecule involved in cellular metabolism. Spermine is a naturally occurring polycationic polyamine crucial for eukaryotic cell growth, present in the nucleus at millimolecular concentrations and tightly bound to chromatin. This study reveals a novel molecular function: spermine acts as a direct free radical scavenger, protecting DNA from hydroxyl radicals. This function differs from previously proposed mechanisms involving charge neutralization or DNA conformational changes. One proposed chemical mechanism involves the hydroxylation of the primary amino group of spermine to form N-hydroxy derivatives, which can be dehydrated to form oximes, subsequently hydrolyzed to dialdehydes. This free radical scavenging activity makes nuclear spermine a potentially key first line of defense against oxidative DNA damage, mutation, and transformation.

C10H26N4

202.3402

202.215

71-44-3

Spermine tetrahydrochloride;306-67-2

1103

Colorless to off-white <29°C powder,>29°C liquid

0.9±0.1 g/cm3

308.4±0.0 °C at 760 mmHg

310-311 °C (dec.)(lit.)

175.6±22.6 °C

0.0±0.6 mmHg at 25°C

1.485

-0.96

4

4

11

14

86.1

0

N([H])(C([H])([H])C([H])([H])C([H])([H])N([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H]

PFNFFQXMRSDOHW-UHFFFAOYSA-N

InChI=1S/C10H26N4/c11-5-3-9-13-7-1-2-8-14-10-4-6-12/h13-14H,1-12H2

N,N′-Bis(3-aminopropyl)-1,4-diaminobutane

Spermine free base, Gerontine, Musculamine, Neuridine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~125 mg/mL (~617.77 mM)

Solubility in Formulation 1: 100 mg/mL (494.22 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)