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At least 19 recordsLinked to original sources
PubMed1985

On the metabolism of amygdalin. 2. The distribution of beta-glucosidase activity and orally administered amygdalin in rats.

The organs of 15-day-old rats had the highest capability to hydrolyze amygdalin and prunasin, and most of this activity is concentrated in the tissues of the small and large intestines. The activity decreased with age. In adult rats, the ability of the organs to hydrolyze prunasin is higher than that of amygdalin and is concentrated in the spleen, large intestine, and kidney (35.0, 15.0, and 8.9 micrograms prunasin hydrolyzed . h-1 . g tissue-1). Minced tissues of the liver, spleen, kidney, and stomach contain more hydrolytic capability than the homogenate of these organs, while the reverse is the case with the small and large intestines. When 30 mg amygdalin was orally administered to adult rats, its distribution after the 1st h was as follows: stomach (0.89 mg), small intestine (0.78 mg), spleen (0.36 mg), large intestine (0.30 mg), kidney (0.19 mg), liver (0.10 mg), and serum (5.6 micrograms/mL). At the end of the 2nd h, the highest amygdalin content was found in the large intestine (0.79 mg).

Administration, Oral↗
PubMedDate not supplied

Amygdalin metabolism and effect on reproduction of rats fed apricot kernels.

Diets containing 10% ground apricot kernels were fed to young and breeding male and female Sprague-Dawley rats. The kernels werE obtained from 35 specific apricot cultivars and divided into groups containing low amygdalin (less than 50 mg cyanide per 100 g), moderate amygdalin (100-200 mg cyanide per 100 g), or high amygdalin (more than 200 mg cyanide per 100 g). Growth of young male rats was greatest in the low- or moderate-amygdalin group which may indicate only that they were more sensitive to the bitter taste of the kernels with high amygdalin contents. In female rats, but not males, liver rhodanese activity and thiocyanate (SCN) blood levels were increased with the high-amygdalin diet, but both male and females efficiently excreted thiocyanate, indicating efficient detoxication and clearance of cyanide hydrolyzed from the dietary amygdalin. No changes in blood chemistry were observed. Although parturition and 3-d survival indices were poor in pups from dams fed a basal semisynthetic diet, offspring of breeding rats fed the high-amygdalin diet for 18 wk had lower 3-d survival indices, lactation indices, and weaning weights than those in the low-amygdalin group. This may indicate that the cyanide present in the milk may not be efficiently detoxified to SCN and excreted by neonates.

Amygdalin↗
PubMed1986

Intestinal first pass metabolism of amygdalin in the rat in vitro.

The intestinal first pass metabolism of amygdalin has been investigated in rat small intestine in vitro. The results show that amygdalin is hydrolyzed to prunasin, essentially in the wall of the proximal jejunum. This specific beta(1-6)hydrolytic cleavage of the terminal glucose residue is pH-dependent and can be inhibited by glucono-delta-lactone, a potent inhibitor of the lysosomal beta-glucosidase of the rat intestine. No substrate competition between phloridzin and lactose vs amygdalin was noted. None of the more common soluble beta- or alpha-enzymatic activities of mammalian intestine (alpha-glucosidase, alpha-amylase) or mammalian liver (beta-galactosidase, beta-glucuronidase) were capable of catalyzing the hydrolysis of the terminal glucose from amygdalin at pH's 5.0, 7.0 or 9.0. Furthermore, no metabolic activity of isolated rat livers toward amygdalin and prunasin was observed within two hours of recirculating perfusion. However, cecal contents of conventional rats, exhibited both amygdalin- and prunasin-hydrolyzing activities. The resulting mandelonitrile dissociates spontaneously into cyanide and benzaldehyde. Therefore, our findings indicate that metabolism of amygdalin to prunasin occurring in the proximal part of jejunum is apparently mediated by enzymatic beta(1-6)glucosidase activity of the gut wall. In contrast, the toxicity of amygdalin due to the release of cyanide obviously requires microbiological activities of the gut flora.

Amygdalin↗
PubMed1985

On the metabolism of amygdalin. 1. The LD50 and biochemical changes in rats.

The mean lethal dose (LD50) of amygdalin in rats was found to be 880 mg/kg body weight (BW) by oral administration. However, when 600 mg/kg BW was administered orally with beta-glucosidase, all the rats died. Total and Mg ATPase activities of the heart decreased with increasing levels of administered amygdalin. When 200 mg/kg BW amygdalin was administered 2.3 mg (11.7% of the dose) was excreted intact over 48 h. Amygdalin, 7.4 mg (18.5% of the dose) was excreted when the dose was 400 mg/kg BW, while 7.5 mg (12.4% of the dose) was excreted as intact amygdalin when the dosage was increased to 600 mg/kg BW. Thiocyanate excreted within the same 48-h period was 7.0, 9.1, and 9.5 mumol representing 18, 11.2, and 7.8% of the 200, 400, and 600 mg/kg BW oral dosage, respectively. With 300 mg/kg BW amygdalin administered intraperitoneally, 4.1 mg amygdalin and 3.9 mumol thiocyanate representing 13.7 and 6.5% of the dose, respectively, was excreted. Excretion of intact amygdalin and thiocyanate was uniform when the dose was low (200 mg), but with higher doses over 70% of the excreted products were detected in the urine during the first 24 h.

Adenosine Triphosphatases↗
PubMedDate not supplied

Blood cyanide levels in mice after administration of amygdalin.

Oral doses of amygdalin and intraperitoneal (i.p.) doses of potassium cyanide (KCN) in the near-lethal range were administered to CD2F1 female mice. Blood cyanide levels were then measured as a function of time. The maximum cyanide level after amygdalin administration was reached at about 11/2 to 2 h and was within the range of values seen after KCN administration. Behaviour of mice correlated with the time of maximum blood cyanide level. Acute distress was observed at times when the cyanide level was highest. There was great variability in the nature and magnitude of the response in individual mice. The ability of the contents of various regions of the gastrointestinal tract and of tumour tissue to release cyanide from amygdalin was assessed. Stomach and upper intestine had little activity while the lower end and the faeces released large amounts. Again, there was a large variation between mice. These results are interpreted to mean that enteric contents are primarily responsible for the release of cyanide from ingested amygdalin. Freshly minced tumour tissue released negligible amounts of cyanide. Ten-fold higher doses of amygdalin administered i.p. produced very small increases in blood cyanide levels and no toxic behaviour. The doses used are comparable to doses which might be ingested by patients receiving oral amygdalin or Laetrile and indicate that oral amygdalin is potentially extremely dangerous.

Administration, Oral↗
PubMed1981

Pharmacology of amygdalin (laetrile) in cancer patients.

Plasma and urine concentrations of amygdalin, whole-blood concentrations of cyanide, and thiocyanate concentrations in serum and urine were determined in cancer patients following intravenous (4.5 g/m2) and oral (500-mg tablet) administration of amygdalin. To measure low plasma concentrations of amygdalin following oral administration a GC/MS assay was developed. Following intravenous administration, concentrations of parent drug as high as 1,401 microgram/ml were observed, with no increase in plasma concentrations of cyanide or serum concentrations of thiocyanate. Plasma elimination of amygdalin was best described by a two-compartment open model with a mean distributive phase half-life of 6.2 min, mean elimination phase half-life of 120.3 min, and mean clearance of 99.3 ml/min. Following oral administration of amygdalin, plasma concentrations were much lower, with peak values of less than 525 ng/ml. Cyanide concentrations increased to values as high as 2.1 microgram/ml whole blood. Thiocyanate concentrations did not increase for several days, plateauing at values as high as 38 microgram/ml serum. Ingestion of almonds by two patients taking oral amygdalin increased cyanide concentrations compared with values obtained after oral amygdalin alone.

Administration, Oral↗
PubMed1982

The pharmacokinetics of amygdalin.

Amygdalin (D-mandelonitrile-beta-D-gentiobioside) is a cyanogenic glycoside claimed to show anti-cancer activity, sold under the incorrect name "Laetrile". For a sensible discussion of its alleged activity and its established toxicity it is necessary that its fate in the organism is known. The pharmacokinetics of amygdalin have been investigated in the Beagle dog after both intravenous and oral administration. The excretion of amygdalin has also been studied in the rat. Amygdalin concentrations were determined by high performance liquid chromatography in plasma ultrafiltrate and urine. The pharmacokinetics of amygdalin after intravenous administration were compared with those of diatrizoate, a model substance for extracellular volume and glomerular filtration. The amygdalin clearance is significantly larger than that of diatrizoate. The volumes of distribution of both substance are the same. After oral administration only a few percents of the amygdalin dose are systemically available. A part of the oral dose is recovered from the urine as prunasin (D-mandelonitrile-beta-D-glucoside).

Administration, Oral↗
PubMed1986

Comparative metabolism of linamarin and amygdalin in hamsters.

Rates of cyanide liberation resulting from hydrolysis of the cyanogenic glycosides linamarin, amygdalin and prunasin by a crude beta-glucosidase prepared from hamster caecum were studied in vitro. In addition, hamster blood cyanide and thiocyanate concentrations were determined at 0.5, 1, 2, 3 and 4 hr after an oral dose of 0.44 mmol linamarin or amygdalin/kg body weight. Plots of cyanide liberated v. time for linamarin and prunasin yielded straight lines. A similar plot for amygdalin was curvilinear, with the rate of cyanide release increasing with time. At 10(-3) M substrate concentrations, the average rates of hydrolysis of prunasin, amygdalin and linamarin were 1.39, 0.57 and 0.13 nmol/min/mg protein, respectively. Lineweaver-Burk plots yielded apparent Km and Vmax values of 3.63 X 10(-5) M and 0.35 nmol/min/mg protein, respectively, for amygdalin, and 7.33 X 10(-3) M and 1.04 nmol/min/mg protein, respectively, for linamarin. Blood cyanide concentrations following amygdalin treatment reached their highest level (130 nmol/ml) 1 hr after dosing and remained elevated until 3 hr after treatment. Blood cyanide concentrations following linamarin treatment reached their highest level (116 nmol/ml) after 3 hr and then declined immediately. Area under the blood cyanide concentration-time curve was 395 nmol-hr/ml for amygdalin and 318 nmol-hr/ml for linamarin. The results suggest a faster rate of enzymatic hydrolysis and cyanide absorption for amygdalin than for linamarin.

Amygdalin↗
PubMed1984

Preparative and analytical separation of amygdalin and related compounds in injectables and tablets by reversed-phase HPLC and the effect of temperature on the separation.

Previous HPLC procedures for amygdalin and related compounds in injectables and tablets were either time consuming or produced inadequate separations of D-amygdalin and its epimer. A study of the effects of temperature on the separation resulted in development of an HPLC method for amygdalin and some related compounds, using water as the mobile phase at 15 degrees C. Multimilligram quantities of amygdalin and related compounds were separated by this preparative procedure. The aqueous mobile phase allows the compounds to be recovered by simple lyophilization of the sample after elution. This permitted the carbon-13 NMR spectrum of the isolated aglyconic epimer of amygdalin to be reported for the first time. D-amygdalin, its L-mandelonitrile epimer (D-epiamygdalin), their hydrolysis products (the epimeric amides and epimeric acids), and the sugar gentiobiose were separated by the method.

Amygdalin↗
PubMed2025

Indel mutation in transcription factor PabHLH2 regulates amygdalin accumulation and kernel bitterness in apricot.

Amygdalin, the phytochemical responsible for the characteristic bitterness of apricot (Prunus armeniaca L.) kernels, also exhibits significant bioactive properties and therapeutic potential. Genetic regulation of amygdalin content is therefore a key objective in apricot breeding programs aimed at quality improvement. In this study, we conducted quantitative trait loci (QTL) mapping to uncover the genetic basis of sweet-bitter differentiation in apricot kernels. We identified a 15-bp insertion/deletion (indel) polymorphism strongly related to kernel bitterness, with marker validation achieving 100% concordance across 601 apricot germplasm accessions. Notably, this polymorphic site is located within the helix-loop-helix (HLH) domain of the basic HLH (bHLH) transcription factor PabHLH2. Protein interaction analyses revealed that the 15-bp deletion variant impaired dimerization capacity, reducing transcriptional activation of downstream targets. Using yeast one-hybrid screening and dual-luciferase reporter assays, we identified PaCYP71AN24 and PaCYP79D16 as direct transcriptional targets of PabHLH2. Functional characterization further indicated that the PabHLH2a variant (harboring the 15-bp insertion) significantly enhanced the promoter activity of these cytochrome P450 genes compared with the deletion variant. Transient overexpression and silencing experiments in apricot kernels further confirmed that the 15-bp insertion positively regulates both PaCYP71AN24/PaCYP79D16 expression and prunasin accumulation, the immediate biosynthetic precursor of amygdalin. Overall, these findings provide mechanistic insights into the allelic variation underlying kernel bitterness and delineate the molecular cascade of amygdalin biosynthesis. The identified molecular markers and functional characterization establish a basis for marker-assisted breeding of low-amygdalin apricot cultivars, supporting the dual-purpose utilization of kernels in food and pharmaceutical industries.

Amygdalin↗
PubMed1980

Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow.

The effect of amygdalin on human acute myelogenous leukemia cells and normal bone marrow granulocyte-monocyte precursors was studied in vitro using soft-gel culture. A pharmaceutical and a clinical source of amygdalin were tested and beta-glucosidase was added to selected cultures to promote the hydrolysis of amygdalin. Acute myelogenous leukemia cells were obtained from two human cell lines designated KG-1 and HL-60. A 50% inhibition of colony formation by both normal and leukemic cells was observed at an amygdalin concentration of 3.5 mg/ml using both drug sources. We found the colony-forming cells from the leukemic cell lines and normal marrow to be relatively resistant to amygdalin and its metabolites in vitro, and there was no selective kill of clonogenic cells from the human leukemia cell lines as compared to normal bone marrow.

Amygdalin↗
PubMed1981

A pharmacologic and toxicological study of amygdalin.

Six patients with advanced cancer were treated with amygdalin (laetrile) at dosages similar to those employed by laetrile practitioners. Amygdalin given intravenously at 4.5 g/sq m/day was largely excreted unchanged in the urine and produced no clinical or laboratory evidence of toxic reaction. Amygdalin given orally at 0.5 g three times daily produced significant blood cyanide levels to 2.1 microgram/mL. No clinical or laboratory evidence of toxic reaction was seen in the six patients taking oral amygdalin at this dosage. One patient, however, challenged with a large intake of raw almonds, had transient symptoms of cyanide toxic reaction with escalating blood cyanide levels. This small study indicates that amygdalin in the doses employed produces few clinical side effects. A definite hazard of cyanide toxic reaction must be assumed, however, and possible long-term side effects remain unknown.

Administration, Oral↗
PubMed1982

A clinical trial of amygdalin (Laetrile) in the treatment of human cancer.

One hundred seventy-eight patients with cancer were treated with amygdalin (Laetrile) plus a "metabolic therapy" program consisting of diet, enzymes, and vitamins. The great majority of these patients were in good general condition before treatment. None was totally disabled or in preterminal condition. One third had not received any previous chemotherapy. The pharmaceutical preparations of amygdalin, the dosage, and the schedule were representative of past and present Laetrile practice. No substantive benefit was observed in terms of cure, improvement or stabilization of cancer, improvement of symptoms related to cancer, or extension of life span. The hazards of amygdalin therapy were evidenced in several patients by symptoms of cyanide toxicity or by blood cyanide levels approaching the lethal range. Patients exposed to this agent should be instructed about the danger of cyanide poisoning, and their blood cyanide levels should be carefully monitored. Amygdalin (Laetrile) is a toxic drug that is not effective as a cancer treatment.

Adolescent↗
PubMed1981

Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue.

Amygdalin, the gentiobioside derivative of mandelonitrile commonly referred to as Laetrile, is presently under intensive investigation as a potential cancer chemotherapeutic agent. Because of this interest, we investigated the activity of beta-glucosidases that cleave glucose from amygdalin and from prunasin (mandelonitrile monoglucoside) in tissues from germ-free rats and in normal and neoplastic human tissues. Rat and human small intestinal mucosa contain high levels of activity of glucosidases that act on both of these cyanogenic glucosides. Release of glucose from these compounds was not detected in any of the human neoplastic tissues examined in the present study. These observations are consistent with reports of cyanide toxicity through the oral use of amygdalin or prunasin and pose serious questions concerning the alleged tumoricidal effect of amygdalin.

Amygdalin↗
PubMedDate not supplied

Experimental studies of the antitumor activity of amygdalin MF (NSC-15780) alone and in combination with beta-glucosidase (NSC-128056).

Amygdalin MF was evaluated alone and in combination with an activating agent, beta-glucosidase, against three transplantable rodent tumors; Ridgway osteogenic sarcoma, Lewis lung carcinoma, and P388 leukemia. In dose-response studies up to the LD20 in normal mice, amygdalin MF alone did not demonstrate significant antitumor activity against any of these three tumor systems. Similarly, at doses not exceeding the LD10 in normal mice, amygdalin MF plus beta-glucosidase did not demonstrate antitumour activity against any of these three tumor systems. Potentiation of the lethal toxicity of amygdalin MF by beta-glucosidase was observed in all studies where the two agents were given in simultaneous combination.

Amygdalin↗
PubMedDate not supplied

Antitumor activity of amygdalin MF (NSC-15780) as a single agent and with beta-glucosidase (NSC-128056) on a spectrum of transplantable rodent tumors.

Experiments are described in which four transplantable rodent tumors (L1210 lymphoid leukemia, P388 lymphocytic leukemia, B16 melanoma, and Walker 256 carcinosarcoma) were used to investigate the antitumor activity of amygdalin MF. Amygdalin MF was given alone and in combination with beta-glucosidase which was administered 1/2 hour prior to amygdalin MF, starting 24 hours after tumor implantation. No antitumor activity was observed in any of the four tumor systems tested with the drug alone or in combined therapy. The combined therapy showed potentiation of toxicity with doses of amygdalin MF greater than or equal to 100 mg/kg.

Amygdalin↗
PubMed1978

A simple method for the estimation of amygdalin in the urine.

A procedure for the estimation of D- and D,L-amygdalin in urine is described. Amygdalin is hydrolyzed by beta-glucosidase and base to benzaldehyde, glucose and cyanide. Benzaldehyde is extracted with methylene chloride and the ultraviolet (UV) absorbence determined at 243 nm. The response of human urine "spiked" with amygdalin was linear between 10 and 75 microgram/ml. Mice administered 100 mg/kg of amygdalin intravenously or orally excreted about 70 and 20% of the administered dose, respectively, over 96 hours. In each instance more than 96% of excreted drug equivalents were obtained within the first 24 hours.

Administration, Oral↗