The recent discovery of the widespread use of SEM in global food industries and in baby food as a result of packaging contamination has focused attention on the toxicity of this substance . The target sites of SEM-HCl toxicity were mainly cartilage and bone. Furthermore, epiphyseal cartilage is the potential target of SEM lathyrogen action (lack of mineralization) that is established at all dose levels . The lesions were much more diverse and serious in young animals, as young animals generally consume more food per body weight during the growing period than adults ; thus, the present study was carried out to study the effect of SEM on cartilage and bone of juvenile rats.
The results of the present study indicated that SEM induced severe osteochondral histological alterations. In the treated group, there was widening and disorganization of the epiphysial cartilage with disruption of the various zones. Some authors  attributed these changes to abnormal widening of the zone of maturing cartilage, which caused the general enlargement of the plate. They added that the main characteristics of SEM are abnormal widening of the hypertrophic zone, with failure to progress to calcification and ossification. However, reduction of the staining intensity of the cartilage matrix reflected decreased polymerization of the cartilage matrix or alteration in the matrix properties caused by inhibition of cross-linking reactions of collagen . It has been hypothesized that fissures specifically occurred in the sites subjected to body weight loading such as the anterior area of the tibia, due to alteration in the matrix properties, which reduce the strength of cartilage, leading to its fragmentation and fissure formation. The presence of collagen fibers around the fragmented plates (detected as an acidophilic zone around the fragments of the epiphyseal plate in H&E sections and as blue-colored fibers in MT-stained sections) was attributed to the poor integration of the extracellular matrix of these ‘repair tissues’ with the matrix of the damaged cartilage; it was also found that, if the cartilage was injured after the period of active growth, the defects were usually filled with connective tissue or fibrous cartilage .
Furthermore, SEM appeared to act as an endocrine disrupter, showing multiple specific mechanisms of action; it showed an antiestrogenic activity as serum estrogen levels were reduced in treated females . As the estrogen hormone plays an important role in endochondral bone formation, particularly during pubertal growth , in addition, estrogenic compounds may accelerate polymerization and facilitate calcium binding, thereby stabilizing the newly synthesized collagen . SEM antiestrogenic activity resulted in decreased bone formation and increased bone resorption. The structure of the bone is maintained by the relationship between bone resorption and formation; thus, activated bone resorption may play an important role in the pathogenesis of bone loss .
The ultrastructure results of the femur in the current study demonstrated that the most prominent changes in osteocytes were mainly degenerative in the form of shortening of cytoplasmic processes, multiple dilated rER, many electron-dense mitochondria, and very irregular nuclei with condensed chromatin; in addition, other cells were also shrunken. It has been reported that SEM induces DNA damage through the formation of hydrogen peroxide; furthermore, SEM-derived free radicals also participate in DNA damage. DNA damage induced by these reactive species may be linked to the degenerative changes observed in oseocytes .
The results of the present study showed that oral administration of SEM during the juvenile period in male albino rats induced multiple osteochondral lesions, leading to failure to achieve normal peak bone mass and defects in development of the epiphyseal plate, which represents a major risk factor for development during early adulthood.
In light of these findings, it is recommended to avoid food products sold in glass jars, especially baby food, and consumers should be advised to use fresh products. In addition to informing the leaders of industry to eliminate SEM from the metal twist caps used with glass jars and identify alternative types of gaskets sealing jars.
There is no conflict of interest to declare.
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