Mannitol

Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: a comparison with other osmotic agents and free radical scavengers.[Pubmed: 15950247]

Neuropharmacology. 2005 Oct;49(5):669-86.

METHODS AND RESULTS:
The basis for the neuroprotectant effect of D-Mannitol in reducing the sensory neurological disturbances seen in ciguatera poisoning, is unclear. Pacific ciguatoxin-1 (P-CTX-1), at a concentration 10 nM, caused a statistically significant swelling of rat sensory dorsal root ganglia (DRG) neurons that was reversed by hyperosmolar 50 mM D-Mannitol. However, using electron paramagnetic resonance (EPR) spectroscopy, it was found that P-CTX-1 failed to generate hydroxyl free radicals at concentrations of toxin that caused profound effects on neuronal excitability. Whole-cell patch-clamp recordings from DRG neurons revealed that both hyper- and iso-osmolar 50 mM D-Mannitol prevented the membrane depolarisation and repetitive firing of action potentials induced by P-CTX-1. In addition, both hyper- and iso-osmolar 50 mM D-Mannitol prevented the hyperpolarising shift in steady-state inactivation and the rise in leakage current through tetrodotoxin (TTX)-sensitive Na(v) channels, as well as the increased rate of recovery from inactivation of TTX-resistant Na(v) channels induced by P-CTX-1. D-Mannitol also reduced, but did not prevent, the inhibition of peak TTX-sensitive and TTX-resistant I(Na) amplitude by P-CTX-1. Additional experiments using hyper- and iso-osmolar D-sorbitol, hyperosmolar sucrose and the free radical scavenging agents Trolox and L-ascorbic acid showed that these agents, unlike D-Mannitol, failed to prevent the effects of P-CTX-1 on spike electrogenesis and Na(v) channel gating.
CONCLUSIONS:
These selective actions of D-Mannitol indicate that it does not act purely as an osmotic agent to reduce swelling of nerves, but involves a more complex action dependent on the Na(v) channel subtype, possibly to alter or reduce toxin association.

Increased amounts of the Aspergillus metabolite D-mannitol in tissue and serum of rats with experimental aspergillosis.[Pubmed: 2499640]

J Infect Dis. 1989 Jul;160(1):95-103.

Several Aspergillus species produce large amounts of the hexitol D-Mannitol in vitro, but it is not known whether these species also produce D-Mannitol in vivo.
METHODS AND RESULTS:
Serum samples and homogenized tissues were analyzed from rats pretreated with cortisone and cyclophosphamide and then given 2 x 10(6) preincubated conidia of Aspergillus fumigatus intravenously. The resulting infection was lethal by 48 h and was characterized by much more severe disease in the liver than in the kidneys, spleen, or lungs. A compound present in increased amounts in the livers and sera of the infected rats was shown to be D-Mannitol by gas chromatography (GC) and GC/mass spectrometry and enzymatically. Quantitative analysis by GC showed that the infected rats had more D-Mannitol in their livers (but not in their lungs or kidneys) after 12 h (P less than .01 at 12, 24, and 36 h) and higher serum D-Mannitol concentrations and serum D-Mannitol/creatinine ratios after 36 h (P less than .05) than did uninfected controls.
CONCLUSIONS:
These results indicate that A. fumigatus can produce and release sufficient D-Mannitol in the tissues of infected animals to raise serum D-Mannitol levels. Thus, D-Mannitol is a potential diagnostic marker for aspergillosis.

D-mannitol, a specific hydroxyl free radical scavenger, reduces the developmental toxicity of hydroxyurea in rabbits.[Pubmed: 8073363 ]

Teratology. 1994 Apr;49(4):248-59.

Hydroxyurea (HU) is a potent mammalian teratogen. Within 2-4 hours after maternal injection, HU causes 1) a rapid episode of embryonic cell death and 2) profound inhibition of embryonic DNA synthesis. A variety of antioxidants delays the onset of embryonic cell death and reduces the incidence of birth defects. Antioxidants do not block the inhibition of DNA synthesis, indicating that early embryonic cell death is not caused by inhibited DNA synthesis. We have suggested that some HU molecules may react within the embryo to produce H2O2 and subsequent free radicals, including the very reactive hydroxyl free radical. The free radicals could cause the early cell death; antioxidants are believed to terminate the aberrant free radical reactions resulting in lessened developmental toxicity.
METHODS AND RESULTS:
To investigate whether hydroxyl free radicals cause the early episode of cell death, pregnant New Zealand white rabbits were injected subcutaneously on gestational day 12 with a teratogenic dose of HU (650 mg/kg) in the presence or absence of 550 mg/kg of D-Mannitol (Man), a specific scavenger of hydroxyl free radicals. Osmotic control rabbits received HU plus 550 mg/kg of xylose (Xyl, a nonactive aldose). At term, the teratologic effects of HU were ameliorated by Man as evidenced by decreased incidences of the expected limb malformations. Xyl exerted no demonstrable effect on HU teratogenesis. Histological examination of limb buds at 3-8 hours after maternal injection, showed that Man delayed the onset of HU-induced cell death by as much as 4 hours. Xyl had no effect. That Man acts within the embryo was shown by performing intracoelomic injections on alternate implantation sites with Man, Xyl, or saline followed by subcutaneous injection of the pregnant doe with HU. Embryos were harvested 3-8 hours later. Limb buds from saline- and Xyl-injected embryos exhibited the typical pattern of widespread HU-induced cell death at 3-4 hours, whereas Man-injected embryos did not exhibit cell death until 5-8 hours.
CONCLUSIONS:
These results are consistent with those reported for antioxidant-mediated amelioration of HU-induced developmental toxicity and with the hypothesis that hydroxyl free radicals are the proximate reactive species in HU-induced early embryonic cell death.

J. Appl. Sci., 2011, 11(16):3044-8.

Thermal Analysis of D-mannitol for Use as Phase Change Material for Latent Heat Storage.[Reference: WebLink]

The aim of this study was to investigate the thermal properties of D-Mannitol as a Phase Change Material (PCM) for latent heat storage system. Heat absorbed by D-Mannitol causes it to undergo a change from the solid to the liquid phase and this heat is stored as the latent heat of fusion. The stored energy can then be retrieved at a later time for various applications.
METHODS AND RESULTS:
The melting point and enthalpy of the fusion of D-Mannitol are important properties and these were determined by Differential Scanning Calorimetry (DSC) measurements. Melting was found to begin at 162.15°C and attained a peak at 167.8°C while the enthalpy of fusion was found to be 326.8 J g"1 for 10°C min"1. Furthermore the change in melting temperature and enthalpy of fusion for different heating rates were studied experimentally by DSC. D-Mannitol's thermal stability was studied using the TG-DTG (thermogravimetry-denvative thermogravimetry) and TG-DTA (thermogravimetry-differential thermal analysis) curves. The TG-DTG curves revealed that thermal decomposition began at 300.15°C. The DTA curve had a sharp endothermic peak at 169.2°C followed by a broad exothermic one at 297°C.
CONCLUSIONS:
The curves showed that D-Mannitol decomposes in one prominent mass loss stage. The measurement of latent heat (enthalpy of fusion), melting point and decomposition point showed that D-Mannitol with a latent heat 326.8 kJ kg-1 and melting temperature 167.8°C is the most suitable PCM candidate for medium temperature applications because of a large temperature difference of 132°C between its melting point and decomposition temperature.