2-(β-D-グルコピラノシルオキシ)-2-メチルプロパンニトリル

RATS WERE FED A SEMIPURIFIED DIET PROVIDING 10% CASEIN SUPPLEMENTED WITH METHIONINE FOR 2 WEEKS, AT WHICH TIME SOME ANIMALS RECEIVED THE SAME DIET WITHOUT THE METHIONINE FOR 4 DAYS. ANIMALS THAT RECEIVED LINAMARIN WERE GIVEN A SINGLE ORAL DOSE CONTAINING 500 OR 250 MG/KG BODY WEIGHT. AT THE LOWER LINAMARIN DOSE DIETARY SUPPLEMENTATION WITH METHIONINE APPEARED TO REDUCE INCIDENCES OF CLINICAL TOXICITY SIGNS AND FATALITIES. DIETARY SUPPLEMENTATION WITH METHIONINE PROVIDED SOME PROTECTION AGAINST THE TOXICITY OF THE LOWER LEVEL OF LINAMARIN ADMINISTERED.

Ingestion of food prepared from insufficiently processed cassava roots with high linamarin levels has been associated with dietary toxicity, particularly with the upper motor neuron disease known as konzo to the African populations. Dietary exposure to linamarin has also been reported as a risk factor in developing glucose intolerance and diabetes. (L630)

Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

FROM THE SEED SKINS OR EMBRYOS OF FLAX...

/GLYCOSIDE IN/ CASSAVA, A TROPICAL PLANT...

THE ISOLATION AND IDENTIFICATION OF LINAMARIN FROM PASSIFLORA WARMINGII IS REPORTED.

FOLLOWING INGESTION BY RATS OF LINAMARIN-CONTAINING CASSAVA, THE EXPERIMENTAL OBSERVATIONS OF CHANGES IN IODINE AND THIOCYANATE METABOLISM CORRELATE WITH THE METABOLIC FINDINGS REPORTED FOR SUBJECTS LIVING IN THE GOITROUS AREA OF THE IDJWI ISLAND. THE ENDEMIC GOITER PREVAILING THERE IS APPARENTLY RELATED TO THE SIMULTANEOUS EFFECT OF IODINE DEFICIENCY AND CONSUMPTION OF LARGE AMOUNTS OF CASSAVA.

INGESTION OF CASSAVA, WHICH CONTAINS THE CYANOGENIC GLUCOSIDE LINAMARIN, BY RATS INDUCED CHANGES IN IODINE AND THIOCYANATE METABOLISM WHICH WERE BOTH QUANTITATIVELY AND QUALITATIVELY IDENTICAL TO THOSE OBSERVED AFTER PROLONGED ADMINISTRATION OF THIOCYANATE.

THE PRINCIPAL CYANOGENIC GLUCOSIDE IN CASSAVA IS LINAMARIN. ADDITION OF PURE LINAMARIN TO A DIET BASED ON 10% VITAMIN-FREE CASEIN DID NOT AFFECT THE WEIGHT GAIN OF RATS. THE ANIMALS THAT RECEIVED THE CASEIN DIET SUPPLEMENTED WITH METHIONINE GAINED MORE WEIGHT THAN THOSE RECEIVING THE UNSUPPLEMENTED DIET. THE AMOUNT OF THIOCYANATE ION EXCRETED IN THE URINE BY THE ANIMALS THAT RECEIVED LINAMARIN WAS HIGHER THAN THAT EXCRETED BY THE ANIMALS THAT DID NOT RECEIVE LINAMARIN AT BOTH LEVELS OF DIETARY METHIONINE. THE PLASMA THIOCYANATE CONCENTRATION WAS ALSO HIGHER FOR LINAMARIN-FED ANIMALS THAN FOR ANIMALS THAT DID NOT RECEIVE LINAMARIN. HIGHER PLASMA THIOCYANATE LEVELS WERE ASSOCIATED WITH A LOWER PERCENTAGE UPTAKE OF RADIOIODINE BY THE THYROID.

A SINGLE ORAL DOSE OF PURE SYNTHETIC LINAMARIN (500 MG/KG) ADMINISTERED TO RATS CAUSED CLINICAL SIGNS, INCLUDING CARDIAC ARRHYTHMIAS AND RESPIRATORY CHANGES. SIMILAR SIGNS WERE OBSERVED IN RATS GIVEN A SINGLE ORAL DOSE OF CYANIDE (6 MG/KG).

WISTAR RATS, ABOUT 100 G IN WEIGHT, WERE DOSED BY STOMACH TUBE WITH PURE LINAMARIN (A MAJOR CYANOGENIC GLUCOSIDE IN CASSAVA). A 50 MG DOSE WAS LETHAL TO 7 OF 10 RATS RECEIVING THIS DOSE.

RATS WERE FED A SEMIPURIFIED DIET PROVIDING 10% CASEIN SUPPLEMENTED WITH METHIONINE FOR 2 WEEKS, AT WHICH TIME SOME ANIMALS RECEIVED THE SAME DIET WITHOUT THE METHIONINE FOR 4 DAYS. ANIMALS THAT RECEIVED LINAMARIN WERE GIVEN A SINGLE ORAL DOSE CONTAINING 500 OR 250 MG/KG BODY WEIGHT. AT THE HIGHER LINAMARIN DOSE ALL ANIMALS DIED WITHIN 5 HOURS AFTER DOSING.