Abstract
BackgroundReducing exposure to toxic environmental agents is a critical area of intervention. Prenatal or postnatal exposure to certain chemicals has been documented to increase the risk of autism spectrum disorder. Propionic acid (PA) found in some foods and formed as a metabolic product of gut microbiota has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental contaminants and drugs that produce or prevent neurotoxicity, and may thereby aid in the treatment of neurodevelopmental disorders such as autism. The present study investigated the protective and/or therapeutic effects of vitamin D against brain intoxication induced by propionic acid (PPA) in rats.MethodsTwenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups of 7. The control group received only phosphate buffered saline; the oral buffered PPA-treated group received a neurotoxic dose of 250 mg/kg body weight/day for 3 days; and the Vitamin D-protected group received 1000 IU/kg/day of alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks, after which the rats were injected with PPA 250 mg/Kg body weight/day for 3 days. The fourth group received PPA 250 mg/Kg body weight/day for 3 days followed by alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks (Vitamin D therapeutic effect). Vitamin D and calcium were measured in the plasma of the four studied groups. Serotonin, interferon gamma (IFN-γ), glutathione-s-transferase activity and DNA double helix breaks were assayed in the brain tissue of the rats for all groups.ResultsThe obtained data showed that the PPA-treated group demonstrated higher plasma vitamin D levels compared to the control rats, together with multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), an increase in IFN-γ and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally, Comet DNA assays showed remarkably higher tail length, tail DNA % damage and tail moment as a neurotoxic effect of PPA.ConclusionsVitamin D showed a greater protective than therapeutic effect on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration of the impaired biochemically measured parameters representing neurochemical, inflammation, and detoxification processes.
Highlights
Reducing exposure to toxic environmental agents is a critical area of intervention
The present study aims to ascertain the protective and therapeutic effects of vitamin D against propionic acid (PPA)-induced autistic features in animal models
The first group of control animals were fed with a normal diet during the experimental period; the second group of PPA-treated rats received 250 mg/Kg body weight/day for 3 days to induce autistic features; the third group consisted of the protective group, and received 1000 IU/kg/day of alpha, 25-dihydroxyvitamin D (3) (1, 25VD) for two weeks, after which they were treated with PPA (250 mg/Kg body weight/day for 3 days)
Summary
Prenatal or postnatal exposure to certain chemicals has been documented to increase the risk of autism spectrum disorder. Results from animal studies may help to identify environmental contaminants and drugs that produce or prevent neurotoxicity, and may thereby aid in the treatment of neurodevelopmental disorders such as autism. Autism spectrum disorder (ASD) is a group of developmental disabilities. ASD affects both the brain and body of young children. These children have atypical development regarding their socialization, communication, and behavior [1]. Despite thousands of studies on the etiological mechanisms of autism, the pathogenesis of these disorders remains baffling, apart from a general belief that they derive from an interaction between several genes and the environment. Only some uncommon viral infections and certain drugs have been conclusively linked to autism [3]
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