The role of ascorbic acid on collagen structure and levels of serum interleukin-6 and tumour necrosis factor-alpha in experimental lathyrism

Abstract

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.