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Protective and restorative potency of Vitamin D on persistent biochemical autistic features induced in propionic acid-intoxicated rat pups.

Alfawaz HA, Bhat RS, Al-Ayadhi L, El-Ansary AK - BMC Complement Altern Med (2014)

Bottom Line: 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.Additionally, Comet DNA assays showed remarkably higher tail length, tail DNA % damage and tail moment as a neurotoxic effect of PPA.Vitamin 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.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Department, Science College, King Saud University, P,O box 22452, Zip code 11495 Riyadh, Saudi Arabia. elansary@ksu.edu.sa.

ABSTRACT

Background: Reducing 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.

Methods: Twenty-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.

Results: The 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.

Conclusions: Vitamin 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.

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Percentage change in serotonin, IFγ and GST in the three treated groups compared to the control.
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Fig2: Percentage change in serotonin, IFγ and GST in the three treated groups compared to the control.

Mentions: Data are presented in Tables 1,2, and3 together with Figures 1,2,3,4, and5. Table 1 lists the plasma levels of vitamin D and calcium presented as the mean ± S.D for the four studied groups. It can be easily noticed that vitamin D was higher in the PPA-treated group compared to the control and, as expected, was remarkably and significantly elevated in the protected and therapeutically treated groups compared either to the control or PPA-treated groups. In contrast, calcium shows non-significant variation between the four studied groups. Figure 1 presents the percentage change of vitamin D and calcium in the treated groups relative to the control (presented as 100%). It can be easily observed that a 33%, 207% and 150% increase in vitamin D levels was recorded for PPA-treated, vitamin D- protected and vitamin D-treated groups, respectively. Figure 1 also demonstrates the non-significant change in calcium levels.Table 1


Protective and restorative potency of Vitamin D on persistent biochemical autistic features induced in propionic acid-intoxicated rat pups.

Alfawaz HA, Bhat RS, Al-Ayadhi L, El-Ansary AK - BMC Complement Altern Med (2014)

Percentage change in serotonin, IFγ and GST in the three treated groups compared to the control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230722&req=5

Fig2: Percentage change in serotonin, IFγ and GST in the three treated groups compared to the control.
Mentions: Data are presented in Tables 1,2, and3 together with Figures 1,2,3,4, and5. Table 1 lists the plasma levels of vitamin D and calcium presented as the mean ± S.D for the four studied groups. It can be easily noticed that vitamin D was higher in the PPA-treated group compared to the control and, as expected, was remarkably and significantly elevated in the protected and therapeutically treated groups compared either to the control or PPA-treated groups. In contrast, calcium shows non-significant variation between the four studied groups. Figure 1 presents the percentage change of vitamin D and calcium in the treated groups relative to the control (presented as 100%). It can be easily observed that a 33%, 207% and 150% increase in vitamin D levels was recorded for PPA-treated, vitamin D- protected and vitamin D-treated groups, respectively. Figure 1 also demonstrates the non-significant change in calcium levels.Table 1

Bottom Line: 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.Additionally, Comet DNA assays showed remarkably higher tail length, tail DNA % damage and tail moment as a neurotoxic effect of PPA.Vitamin 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.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Department, Science College, King Saud University, P,O box 22452, Zip code 11495 Riyadh, Saudi Arabia. elansary@ksu.edu.sa.

ABSTRACT

Background: Reducing 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.

Methods: Twenty-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.

Results: The 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.

Conclusions: Vitamin 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.

Show MeSH
Related in: MedlinePlus