LYSOSOMAL STORAGE IN SWAINSONA SPP. TOXICOSIS: AN INDUCED MANNOSIDOSIS

Abstract

Ingestion of Swainsona spp. by grazing livestock results in a chronic disease characterized by neurological disturbances and intense vacuolation of cells in most organs. Experiments were carried out using Swainsona canescens and evidence is presented to show that tissues from affected animals contain high levels of mannose-rich oligosaccharides and that the plant contains an inhibitor of lysosomal alpha-mannosidase. It is concluded that ingestion of Swainsona induces a lysosomal storage disease, biochemically and morphologically similar to genetically determined mannosidosis. The role of this process in relation to Swainsona toxicosis is discussed.

Spontaneous Lysosomal Storage Disease Caused by Sida carpinifolia (Malvaceae) Poisoning in Cattle

“…These cellular changes were similar to those reported previously in cattle, 16 goats, 7,13,19 sheep, 33 and ponies 25 poisoned by S. carpinifolia. Similar lesions were also reported in cases of poisoning by plants that contain the alkaloid swainsonine, 1,3,4,9,10,12,20,22 as well as in cases of inherited alpha-mannosidosis in cattle, 21,39 humans, 29 domestic cats, 5,27 and the guinea pig. 28 As in the inherited disease, in the acquired form of alpha-mannosidosis, the alkaloid swainsonine inhibits lysosomal enzyme alpha-mannosidase, 6,8,11,14 resulting in the storage and excretion of partially impaired oligosaccharides.…”

The storage products in genetic and swainsonine-induced human mannosidosis

“…It is a potent inhibitor of a-D-mannosidase activity (Dorling et al, 1980). Prolonged ingestion of swainsonine by animals leads to a neurological disorder that is a phenocopy of the genetically induced lysosomal storage disease mannosidosis (Dorling et al, 1978).Mannosidosis is characterized by accumulation in cells, and excretion in the urine, of mannose-rich oligosaccharides resulting from a deficiency of lysosomal a-D-mannosidase (Jolly et al, 1981). Swainsonine is a lysosomotropic compound and accumulates rapidly in lysosomes of normal human fibroblasts in culture to produce inhibition of intracellular lysosomal a-D-mannosidase (Chotai et al, 1983).…”

Isolation and Characterization of Swainsonine from Texas Locoweed (Astragalus emoryanus)

“…Swainsonine (1,2,8-trihydroxyoctahydroindolizine) is an indolizidine alkaloid that was originally isolated from the Australian plant, Swainsona canescens (4). The structure of this compound is shown in Figure 1.…”

“…In addition, this alkaloid has been found to be a potent inhibitor of glycoprotein processing (2,3,(6)(7)(8)(9)(10)16), by virtue ofthe fact that it inhibits the processing glycosidase, mannosidase 11 (15 4 by the addition of acetic acid. An aliquot (200 ml) of this solution was then applied to a 4 x 40 cm column of Dowex-50-NH4', and the column was washed with about 2 L of H20.…”

“…One g of the lyophilized brown powder was dissolved in about 25 ml of H20, adjusted to pH 4 with acetic acid and applied to a 2 x 30 cm column of Dowex-50-NH4'. The column was washed with 250 ml of H20, and the swainsonine was eluted with a linear gradient of NH40H, prepared by placing 200 ml of H20 in the mixing chamber and 200 ml of 0.5 M NH40H in the other chamber.…”