ascorbic-acid and Lathyrism

Topics: Aminopropionitrile; Animals; Ascorbic Acid; Collagen; Connective Tissue; Copper; Cross-Linking Reagents; Diet; Dietary Proteins; Drug Interactions; Elastin; Energy Intake; Extracellular Matrix; Flavonoids; Genes; Homocysteine; Lathyrism; Manganese; Monoamine Oxidase Inhibitors; Nutritional Physiological Phenomena; Penicillamine; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; Procollagen-Proline Dioxygenase; Protein Biosynthesis; Protein-Lysine 6-Oxidase; Proteins; Proteoglycans; Pyridoxine; Riboflavin; Thiamine; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins; Zinc

It is apparent that significant progress has been made in our understanding of the biosynthesis, modifications, and maturation of collagen and elastin. We now recognize and partially understand special reactions involved in hydroxylations within the cell and complex cross-linking processes occurring outside the cell. Recent experiments (191) have shown that in human diploid fibroblast cultures of limited doubling potential (191) the hydroxylation of collagen prolyl residues appears to be "age" or passage-level dependent. With increasing passage level of these cultures, both the ascorbate requirements and the extent of collagen hydroxylation decrease. "Young" cell cultures have a strong requirement for complete hydroxylation and without ascorbate there is only about 50% of the normal level. "Middle-aged" cultures show higher hydroxylation without and full hydroxylation with ascorbate, whereas "old" (or cultures close to "senescence") are incapable of full hydroxylation with or without ascorbic acid. Although the overall system may show some deterioration with increasing passage levels, it appears that with increasing passage levels other components in the cell replace the ascorbate dependence of the hydroxylase system to a greater exten. In some ways, aging WI-38 cultures begin to resemble some transformed cells in their biochemical reactions, although they continue to remain diploid and eventually lose the ability to replicate. It is not yet known whether old animals can produce collagen, which may now be underhydroxylated, perhaps contributing to certain senescent changes. Careful examination of the hydroxylation index of collagen produced in organoid cultures of tissue biopsies as a function of donor age might be informative, particularly if one looks at the quality of collagen by employing collagenase and other proteolytic digests with collagen (191). One could comare the levels of frequent and characteristic peptide triplet sequences such as Gly-Pro-Hyp to Gly-Pro-Pro, Gly-Ala-Hyp to Gly-Ala-Pro, or Gly-Pro-Hyl to Gly-Pro-Lys and others for evaluation of hydroxylation throughout the entire molecule or at selected sequences.

Topics: Amino Acid Sequence; Animals; Antibody Specificity; Ascorbic Acid; Collagen; Connective Tissue; Copper; Ehlers-Danlos Syndrome; Elastin; Epitopes; Homocystinuria; Humans; Hydralazine; Lathyrism; Marfan Syndrome; Molecular Conformation; Platelet Aggregation; Procollagen-Proline Dioxygenase; Skin Diseases; Syndrome

Topics: Anemia; Animals; Ascorbic Acid; Biomechanical Phenomena; Cicatrix; Collagen; Denervation; Fibrin; Fibroblasts; Glucocorticoids; Glycoproteins; Glycosaminoglycans; Granulation Tissue; Guinea Pigs; Histamine; Humans; Lathyrism; Microbial Collagenase; Oxygen; Rabbits; Rats; Species Specificity; Stress, Physiological; Time Factors; Wound Healing; Wounds and Injuries

Lathyrism is characterized by defective collagen synthesis due to inhibition of lysyl oxidase, an enzyme essential for interfibrillar cross-linking. The lathyritic agent beta-aminoproprionitrile (beta-APN) is considered an appropriate agent for studying connective tissue metabolism. We investigated the effects of ascorbic acid on collagen structure and serum cytokine levels in experimentally induced lathyrism. Forty Wistar rats weighing 200-300 g were used in the study: three test groups of 10 rats each (groups 2, 3 and 4) and 10 rats used as a control group (group 1). Experimental lathyrism was induced with daily subcutaneous injections of beta-APN in the test groups for 40 days. On the 40th day, skin biopsies were taken from the control group (group 1) and group 2, to evaluate the effect of beta-APN on dermal collagen. After the 40th day, 10 rats received ascorbic acid 100 mg/kg intraperitoneally daily for 15 days (group 3) and 10 rats (group 4) received no medication and served as a control for group 3. On the 55th day, skin biopsies were taken from groups 3 and 4. Serum concentrations of interleukin-6 and tumour necrosis factor-alpha were assessed in each group by enzyme-linked immunosorbent assay. Ultrastructural examination of the skin biopsies in group 1 revealed normal-appearing epidermal and dermal structures. Group 2 showed disorganization of the epidermis and collagen structure, and vacuolization of the endoplasmic reticulum in fibroblasts. In group 3, ultrastructural examination revealed significant improvement in the structure of dermal collagen after administration of ascorbic acid, whereas the changes in group 4 were unremarkable. Ascorbic acid administration significantly decreased the concentrations of serum cytokines in group 3 compared with group 2 (P < 0.001). Ascorbic acid administration significantly improved dermal collagen structure and serum cytokine levels in experimental lathyrism.

Topics: Animals; Ascorbic Acid; Collagen; Collagen Diseases; Interleukin-6; Lathyrism; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Neurolathyrism is a neurological condition seen among people who eat the seeds of Lathyrus sativus (LS) as a principal source of food energy for 2 months or more. It is characterized by severe muscular rigidity and paralysis of the lower limbs. beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid is the principal toxin found in the seed. No experimental animal model for neurolathyrism could be produced by feeding either the seeds or the toxin, although the condition has been known for centuries. We discovered that experimental neurolathyrism could be produced in guinea pigs and primates that needed an external supply of ascorbic acid by making them subclinically deficient in ascorbic acid and feeding them the seeds of LS or extracts thereof. Autoclaving the seeds of LS with lime removes the toxin.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Fabaceae; Food Contamination; Guinea Pigs; Haplorhini; Lathyrism; Male; Muscular Diseases; Plants, Medicinal

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Guinea Pigs; Lathyrism; Male

Topics: Aging; Aminopropionitrile; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Cattle; Collagen; Copper; Dietary Carbohydrates; Dietary Proteins; Energy Intake; Fetus; Lathyrism; Longevity; Macromolecular Substances; Molecular Weight; Muscle Development; Muscles; Protein Binding; Skin; Swine; Vitamin D; Zinc

Topics: Aminopropionitrile; Animals; Ascorbic Acid; Borohydrides; Carbon Isotopes; Cell Line; Collagen; Connective Tissue; Fibroblasts; Glycosaminoglycans; Hydroxylation; Hydroxylysine; Isoniazid; Lathyrism; Lysine; Mice; Oxidation-Reduction; Proline; Protein Biosynthesis; Semicarbazides; Solubility; Time Factors; Tritium