CryoNet #33348 - #33349

CryoNet - Thu 24 Feb 2011

    #33348: could limonene eliminate cryoprotectant toxicity? [oberon]
    #33349: Re: CryoNet #33340 [Gerald Monroe]

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Message #33348
Date: Wed, 23 Feb 2011 06:35:05 -0800 (PST)
From: [email protected]
Subject: could limonene eliminate cryoprotectant toxicity?

In ulcer models, limonene offers complete protection against ethanol toxicity. It is here suspected that this protection may extend beyond ethanol to other cryoprotectants. Limonene is nontoxic to humans, crosses the blood brain barrier, exerts sedative and anti-dementia effects, and may inhibit breast cancer. IMHO, limonene is an example of a protective substance that merits explicit testing for vitrification solution toxicity reduction.

Chem Biol Interact. 2011 Jan 15;189(1-2):82-9. Epub 2010 Oct 8.
Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and ?-pinene: involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E?.
Rozza AL, Moraes Tde M, Kushima H, Tanimoto A, Marques MO, Bauab TM, Hiruma-Lima CA, Pellizzon CH. Morphology Department, Biosciences Institute, Univ. Estadual Paulista, Botucatu, SP, Brazil.
Abstract
  Citrus lemon (CL) belongs to Rutaceae family and is popularly known in Brazil as limao siciliano. The phytochemical analysis of CL fruit bark essential oil showed two majority components, limonene (LIM) and ?-pinene (PIN). This study aimed to evaluate the gastroprotective mechanism of action from CL, LIM and PIN in ethanol- and indomethacin-induced gastric ulcers and its in vitro anti-Helicobacter pylori activity. After ethanol-induced gastric ulcer, the ulcer area was measured and the stomachs were destined to histology (HE and PAS), immunohistochemistry for HSP-70 and VIP and glutathione (GSH) measurement. The involvement of nitric oxide (NO) and sulfhydryl (SH) compounds was determined. The ulcer area for indomethacin-induced gastric ulcers was measured. PGE? concentration was biochem
 ically measured. The minimum inhibitory concentration (MIC) against H. pylori was determined in vitro. In ethanol model, CL and LIM demonstrated 100% of gastroprotection, while PIN did not e
 xert effective gastroprotection (53.26%). In the indomethacin model, CL and LIM offered effective gastroprotection but PIN did not show gastroprotective effect. The gastric ulcer area of rats pretreated with NO-synthase inhibitor or SH-blocker was decreased in comparison to the control group. The MIC obtained for CL was 125 ?g/mL, for LIM was 75 ?g/mL and for PIN was 500 ?g/mL. The gastroprotective effect of CL and LIM was involved with increasing in mucus secretion, HSP-70 and VIP, but not with GSH, NO or SH compounds. CL gastroprotective mechanism is involved with PGE?. PIN did not present gastroprotective activity.
Copyright C 2010 Elsevier Ireland Ltd. All rights reserved.
PMID: 20934418

Chem Biol Interact. 2009 Aug 14;180(3):499-505. Epub 2009 May 3.
Effects of limonene and essential oil from Citrus aurantium on gastric mucosa: role of prostaglandins and gastric mucus secretion.
Moraes TM, Kushima H, Moleiro FC, Santos RC, Rocha LR, Marques MO, Vilegas W, Hiruma-Lima CA. Sao Paulo State University, Department of Physiology, Rubiao Junior, cp 510, CEP 18618-000, Botucatu, Sao Paulo, Brazil.
Abstract
  Essential oil from Citrus aurantium and the monoterpene limonene are widely used flavoring agents that are found in some common food items. This specie is also used medicinally throughout the world to treat gastritis and gastric disorders. Therefore, biological assays were performed in vivo on essential oil of C. aurantium (OEC) and its majority compound limonene (LIM) to evaluate their effect on gastric mucosa. The OEC (250 mg/kg, p.o.) and LIM (245 mg/kg, p.o.) provided effective (99%) gastroprotection against lesions induced by absolute ethanol and NSAID (non-steroidal anti-inflammatory drug) in rats. OEC and LIM do not interfere with gastric H(+) secretion, serum gastrin or glutathione (GSH) level in gastric mucosa. But the gastroprotective action of OEC and LIM occurs due to an incr
 ease in the gastric mucus production induced by conserving the basal PGE(2) levels after challenge by agents harmful to the gastric mucosa. Given that LIM and OEC are excellent flavoring age
 nts and also present gastroprotective actions, they can be regarded as a promising target for the development of a new drug for the prevention of gastric damage.
PMID: 19410566

Limonene crosses the blood brain barrier to exert a sedative effect.

J Nutr Sci Vitaminol (Tokyo). 2009 Aug;55(4):367-73.
Sub-chronic effects of s-limonene on brain neurotransmitter levels and behavior of rats.
Zhou W, Yoshioka M, Yokogoshi H. Laboratory of Nutritional Biochemistry, Global COE Program in the 21st Century, Graduate School of Nutritional and Environmental Sciences, The University of Shizuoka, Yada, Suruga, Shizuoka, Japan.
Abstract
  The present study was designed to gain insight into the effects of s-limonene on the brain after 1-wk administration. For this purpose, neurotransmitters such as dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamic acid (Glu) and some of their metabolites (DOPAC and 5-HIAA) were determined by HPLC-ECD and amino acid analyzer after 1-wk administration of s-limonene of different concentrations (0, 5, 25, 50 mg/kg). Significant changes, such as GABA, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT, were confirmed. At the same time, basal hypothalamic-pituitary-adrenal (HPA) activity after 1-wk administration of s-limonene was evaluated by corticosterone. Considering the increment of GABA and the changes of other neurotransmitters, anti-stress effects after 1-wk administrat
 ion were observed. The experimental results showed that s-limonene could inhibit HPA activity under physical stress and this anti-stress effect of s-limonene may act through the GABA(A) rece
 ptor.
PMID: 19763039
Free text>
http://www.jstage.jst.go.jp/article/jnsv/55/4/367/_pdf

Limonene exerts an anti-dementia effect.

Nutr Neurosci. 2009 Apr;12(2):57-64.
Components of lemon essential oil attenuate dementia induced by scopolamine.
Zhou W, Fukumoto S, Yokogoshi H. Laboratory of Nutritional Biochemistry and G-COE Program in the 21st Century, Graduate School of Nutritional and Environmental Science, University of Shizuoka, Shizuoka, Japan.
Abstract
  The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil c
 omponents could inhibit acetylcholinesterase activity in vitro using the Ellman method.
PMID: 19356307

Limonene is bioavailable, and is stored in adipose tissue.

Nutr Cancer. 2010 Aug;62(6):783-8.
Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content.
Miller JA, Hakim IA, Chew W, Thompson P, Thomson CA, Chow HH. Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724, USA.
Abstract
  d-limonene is a bioactive food component found in high concentration in citrus peel oil with anticancer effects in preclinical studies of mammary carcinogenesis. Extrapolation of preclinical data to human cancer is limited, in part, by inadequate information on the oral bioavailability and tissue disposition of d-limonene in humans. As a fat-soluble compound, d-limonene is more likely to deposit in fatty tissues such as the breast. To assess disposition of d-limonene in humans, we conducted a pilot study of oral d-limonene-rich lemonade. Following a 1-wk washout period devoid of citrus, healthy adults consumed 40 oz. of freshly prepared lemonade containing 500 to 600 mg d-limonene daily for 4 wk. On the first and last consumption days, blood and buttock fat biopsy were collected. Matched
  preintervention and postintervention fat biopsies (n = 7), and matched preintervention and postintervention plasma samples (n = 6), were analyzed for d-limonene levels using gas chromatogra
 phy and mass spectrometry. There was a significant increase in d-limonene levels in the fat biopsies after 4 wk (P = 0.009); initial levels ranged from nondetectable to 7.79 micromol/kg tissue, and postintervention levels ranged from 53.6 to 294 micromol/kg tissue. Plasma d-limonene levels increased from 0.35 to 0.72 micromol/l initially to postintervention levels of 0.54 to 1.65 micromol/l (P = 0.016). Postintervention adipose d-limonene levels were 51.0 to 195 times higher than plasma levels (P = 0.009). Our results demonstrate accumulation of d-limonene in adipose tissue after oral dosing and support additional studies of d-limonene for chemoprevention in tissues such as the breast that are comprised of a significant fat fraction.
PMID: 20661827

Limonene is safe for humans (but not insects).

Altern Med Rev. 2007 Sep;12(3):259-64.
D-Limonene: safety and clinical applications.
Sun J. Thorne Research, PO Box 25, Dover, ID 83825, USA.
Abstract
  D-limonene is one of the most common terpenes in nature. It is a major constituent in several citrus oils (orange, lemon, mandarin, lime, and grapefruit). D-limonene is listed in the Code of Federal Regulations as generally recognized as safe (GRAS) for a flavoring agent and can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream, and pudding. D-limonene is considered to have fairly low toxicity. It has been tested for carcinogenicity in mice and rats. Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor. Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic,
  or nephrotoxic risk to humans. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. Being a solvent of cholesterol, d-limonene has been u
 sed clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer.
PMID: 18072821
Free text>
http://www.thorne.com/altmedrev/.fulltext/12/3/259.pdf

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Message #33349
References: <[email protected]>
From: Gerald Monroe <[email protected]>
Date: Wed, 23 Feb 2011 20:42:12 -0600
Subject: Re: CryoNet #33340

--bcaec53f8f63508656049cfe2aff

         Oregon death with dignity act :

Proposal : Use the death with dignity act to perform suspended animations.
I use the word "suspended animation" to differentiate a cryonics procedure
where the patient is actually physiologically dead several minutes at a
minimum and a preservation where the patient never physiologically dies at
all.

     Criteria :  Patient must be terminally ill with less than 6 months left
(won't help patients developing dementia, alas), must convince 2 physicians,
must wait 15 days.

Proposal : Have a physician prescribe a patient a "lethal" dose of drugs
that will stop the heart and cause loss of consciousness but not cause
destruction of neurons.  Patient is connected to a shut down bypass machine,
with a cryonics team that is fully ready for a complete preservation
standing by in the next room.  Patient self administers the drugs when
ready, cryonics team gets ready, the very moment the patient's heart stops
the team rushes in the room.  Hyper-oxygenate the patient beforehand, and
take other measures to protect from a minute or two of ischemia.  I think it
is reasonable to think that doing this way would allow far more consistent
outcomes than the current method.

        I KNOW that I am not the first person to think of this.  It is
immediate and obvious once you look at the case reports that Mike Darwin has
published.  The best case he ever did still had some ischemia because the
patient was not connected to bypass from the beginning.  Better preservation
boost the likelihood of revivals with acceptable amounts of memory loss.

     Why doesn't Alcor or CI have a lab in Oregon to take advantage of this
law?

--bcaec53f8f63508656049cfe2aff

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