Human Lathyrism Research Articles

An epidemiological study on incidence and determinants of Lathyrism

Introduction: Human lathyrism continues to be a public health problem in central India. While osteolathyrism, as such, is not a public health problem, neurolathyrism is of particular importance especially in central parts of India. In particularly Rewa, Satna, Sidhi, Sagar, Seoni, Hoshangabad and Chhattisgarh area of Madhya Pradesh bear the brunt of lathyrism. Ganapathy and Dwivedi (1961) carried out epidemiological study in estate of Vindhya Pradesh (now part of Madhya Pradesh). The sale of L. sativus has been banned in many states in India, but there has not been an effective ban on its cultivation. Lathyrus sativus is hardy crop and survives adverse agricultural conditions. For this reason it has become a main stay of some Indian diets, especially under famine conditions. India farmers continue to grow this pulse despite their awareness of its poisonous nature. It is difficult to provide an alternate crop that would grow under the semi-arid condition of these areas. In recent times, the problem has acquired new dimensions, which hold out possibilities of wider dissemination of the disease. It was probably true that the consumption of Lathyrus seeds had dropped during recent times, but this was probably because other crops like wheat, barley, lentils and Bengal gram had flourished. Material & Method: In order to study the recent trends of lathyrism, the same area and technique have been adopted as were follow by Ganapathy & Dwivedi (1961) and Dwivedi and Prasad (1964). Revisit to study the same area where detail epidemiological work was carried out and reported by Dwivedi & Prasad (1964). They were the following 18 village of Rewa and 10 village of Satna districts. The other part of study included the collection of information of occurrence of cases occurred during the last 10 years period i.e. case occurring from 1975 to 1982. The area of survey restricted to Rewa division to determine those factor responsible for secular variations in the prevalence of disease

In search of a new therapeutic target for the treatment of genetically triggered thoracic aortic aneurysms and cardiovascular conditions: insights from human and animal lathyrism

Lathyrism, or the effect of certain plants on connective tissue disruption, particularly involving the vascular and skeletal systems, especially aortic dissection/rupture, has been well documented in animals. Its impact on the pathogenesis of connective tissue diseases in humans is still unclear. An extensive review of the scientific literature from the 1800s until the present time was performed to examine the common pathways between animal and human lathyrism and genetically triggered thoracic aortic aneurysms and cardiovascular conditions in humans, with special focus on the identification of potential therapeutic targets. Search areas covered the following subjects: lathyrism/spontaneous aortic dissection/rupture in animals; beta-aminopropionitrile, semicarbazide and their effects; collagen and elastin synthesis and cross-linking; genetic and molecular biology characteristics of the genetically triggered thoracic aortic conditions. Search results demonstrate Marfan syndrome as a model for the genetically triggered thoracic aortic aneurysms, has been linked to mutations of the fibrillin-1 gene, via transforming growth factor beta-1. Several other conditions do not share this mutation. Inhibition of semicarbazide-sensitive amine oxidase [vascular adhesion protein-1 (VAP-1)] in animals has been shown to result in aortic dilatation due to disruption of elastin cross-linking. Significantly low activity of this enzyme was identified in annulo-aortic ectasia; a condition similar to Marfan syndrome. In conclusion, the precise molecular and genetic pathways responsible for the clinical findings in Marfan syndrome and related conditions remain unclear. Observational and experimental findings relating to the vascular and systemic effects of molecular pathways implicated in the phenomenon of animal and human lathyrism suggest that VAP-1 seems to be involved in the molecular and developmental pathways of the genetically triggered thoracic aortic diseases and thus could be a potential therapeutic target for these conditions.

Factors affecting β-ODAP content in Lathyrus sativus and their possible physiological mechanisms

A neuroexcitatory non-protein amino acid, β- N-oxalyl- l-α,β-diaminopropionic acid (β-ODAP), present in the seeds of the hardy legume crop grass pea ( Lathyrus sativus L .), was considered responsible for human lathyrism. The levels of β-ODAP were reported to vary in different tissues during plant development, and to be affected by a wide range of environmental stresses. In this paper, dynamic changes in β-ODAP level at specific stages of plant development as well as the influences of various environmental factors, including nutrient deficiency, drought, salinity, toxic heavy metals, and Rhizobium symbiosis on β-ODAP levels were analyzed, highlighting the relationship between changes in β-ODAP concentrations and Rhizobium growth. Possible mechanisms underlying β-ODAP accumulation are proposed and future research is suggested.

From soil to brain: Zinc deficiency increases the neurotoxicity of Lathyrus sativus and may affect the susceptibility for the motorneurone disease neurolathyrism

Zinc deficiency and oversupply of iron to the roots of grass pea (Lathyrus sativus) induce increases in the content of the neurotoxin β-l-ODAP (3-oxalyl-l-2,3-diaminopropanoic acid) in the ripe seeds. The transport of zinc to the shoots is enhanced by the addition of β-l-ODAP. The neurotoxin of L. sativus is proposed to function as a carrier molecule for zinc ions. Soils, depleted in micronutrients from flooding by monsoon rains (Indian subcontinent) or otherwise poor in available zinc and with high iron content (Ethiopian vertisols), may be responsible for higher incidence of human lathyrism, one of the oldest neurotoxic diseases known to man. A role for brain zinc deficiency in the susceptibility for lathyrism is postulated.

Pattern of Lathyrus sativus (grass pea) consumption and beta-N-oxalyl-α-β-diaminoproprionic acid (β-ODAP) content of food samples in the lathyrism endemic region of northwest ethiopia

Grass pea, a legume whose consumption is associated with human lathyrism, is an important food crop among the poorer sectors of society in many parts of Ethiopia. A nutritional survey, focussing on the preparation and consumption of grass pea, in 224 families of two villages of a lathyrism endemic area in northwestern Ethiopia has been undertaken. Grass pea is grown in only one of the two villages. Raw as well as cooked food samples were collected and the levels of β-ODAP determined by the OPT method. Grass pea foods were also prepared in the laboratory following methods used in the villages and analyzed for their toxin level to derive information if certain procedures were capable of reducing the level of toxin. Steeping grass pea in excess water leaches out ca 30% of the β-ODAP. Grass pea bread ( kitta) and roasted seeds ( kollo) showed elevated levels of β-ODAP compared to the seeds used in the preparation of these foods. Lower levels of β-ODAP were found in boiled snacks ( nifro) and the flour form ( shiro).

Gliotoxic properties of the Lathyrus excitotoxin β-N-oxalyl- l-α,β-diaminopropionic acid (β- l-ODAP)

β-N-Oxalyl- l-α,β-diaminopropionic acid (β- l-ODAP) is an excitatory amino acid agonist found in the seeds of Lathyrus sativus that is believed to be the major causative agent in the pathology of human lathyrism. We have found that in addition to its previously recognized neurotoxic properties, β- l-ODAP is also gliotoxic. When added to cultures of neonatal rat astrocytes, β- l-ODAP induced a series of morphological changes (e.g., extensive vacuole formation, pale and swollen nuclei with obvious nucleoli, and cellular swelling) that led to the eventual lysis of the glial cells. If the β- l-ODAP was removed prior to the lysis of the astrocytes, many of the early morphological changes appeared to be reversible. When quantitated by a loss of the lactate dehydrogenase activity, β- l-ODAP lysed the astrocytes with an LD 50 of 2.1 ± 0.2mM following 48 h of exposure. Lower concentrations of β- l-ODAP were found to be more toxic if the duration of the exposure was increased. The results suggest that the overall impact of the toxin on the CNS may represent the cumulative action of β- l-ODAP at a number of distinct points on both neurons and astrocytes. The potential that these multiple sites of action may affect the normal regulation of extracellular glutamate and, consequently, disturb the balance between its normal and pathological roles is discussed.

Intoxication by the chickling pea (Lathyrus sativus): nervous system and skeletal findings.

Two hundred patients with chronic neurolathyrism were examined 25-35 years after the appearance of signs and symptoms of intoxication of the chickling pea. Their daily food intake, in a German forced labor camp during World War II, consisted of 400 g Lathyrus sativus peas cooked in water plus 200 g bread baked of barley and straw. Apart from the classic signs of neurolathyrism, i.e., a spastic paraparesis, in five cases, the skeletal findings observed were similar to experimental osteolathyrism. There was an absence of ossification centers of the iliac creasts, ischial tuberosities and vertebrae; and bowing with thickening of the femoral shaft also occurred. These bony changes in human lathyrism have not been described before.

Use of khesari (lathyrus sativus) in chick diets

1. Broiler chicks, reared for 14 d in battery brooders, were given diets containing 100, 222 or 367 g/kg of khesari meal (Lathyrus sativus) in three different experiments. 2. Birds receiving raw khesari consumed less food and grew more slowly than birds receiving a maize‐soya diet. Supplementation with DL‐methionine did not improve the nutritive value of khesari diets, but the inclusion of L‐tryptophan produced a positive response. 3. When khesari was either autoclaved or heated in a commercial “ micronisation “ process and then incorporated at 367 g/kg in a balanced chick diet, growth and efficiency of food utilisation were at least equal to those obtained with a maize‐soya diet. 4. Khesari depresses chick growth when fed raw, but is an excellent protein source for growing chicks if fed after a suitable heat treatment. Since the component in raw khesari which is toxic to chickens is heat‐labile, it is probably not the same factor that is responsible for human lathyrism.

Penicillamine-induced skin lesions. A possible example of human lathyrism

Penicillamine-induced skin lesions. A possible example of human lathyrism

Central effects of beta-N-oxalyl-alpha,beta-diaminopropionic acid and other lathyrus factors.

ALTHOUGH an association between β-aminopropionitrile derivatives and osteolathyrism of experimental animals seems well established1, there is less certainty concerning the nature of toxic substances present in Lathyrus species responsible for human neurolathyrism2. Acute neurological manifestations are produced in some laboratory animals by L-α,γ-diaminobutyric acid (present in numerous Lathyrus species, but not in L. sativus)3,4, by β-cyano-L-alanine (present in Vicia sativa and V. angustifolia, possible contaminants of L. sativus)5 and by (β-N-oxalyl-L-α,β-diaminopropionic acid (recently isolated from L. sativus)6. The degree of susceptibility to these toxic agents varies between different animal species, and it has yet to be demonstrated whether these substances do, in fact, produce human lathyrism. Nevertheless, in view of the potent effects of many relatively simple amino-acids on mammalian central neurones7, these lathyrus factors are of considerable interest. Consequently an investigation has been made of the action of these and related compounds on single nerve cells of cats anaesthetized with pentobarbitone.

Neurotoxic compounds of the seeds of lathyrus sativus

The seeds of Lathyrus sativus responsible for human lathyrism in India have been examined for toxic components. Four ninhydrin-positive substances were detected in the 30% aqueous ethanol extract by paper chromatography, of which two are present in appreciable amounts. The most prominent one has been isolated in crystalline form and studied for chemical and physiological (neurotoxic) properties and identified as (-)-β-oxalylaminoalanine. The second seems to be homoarginine. The other minor components have still to be identified.

Alkaline Phosphatase of the Serum in Experimental Lathyrism of the White Rat

SummaryNo significant changes in the concentration of alkaline phosphatase of the serum were observed in rats in which experimental lathyrism was produced by feeding diets containing 50% of sweet pea (Lathyrus odoratus) seed. This does not confirm the observations of Rudra and Bhattacharya in which the phosphatase values were markedly increased in human lathyrism.