ubiquinone and propionic-acid

Propionic acid (PPA) is a short-chain fatty acid produced endogenously by gut microbiota and found in foodstuffs and pharmaceutical products as an additive. Exposure to PPA has been associated with the development of autism spectrum disorder (ASD). The purpose of this study was to investigate the protective effect of acetyl-L-carnitine (ALCAR) and liposomal Co-enzyme Q10 (CoQ10) against cerebral and cerebellar oxidative injury, inflammation, and cell death, and alterations in ALDH1A1-RA-RARα signaling in an autism-like rat model induced by PPA. The rats were treated with PPA and concurrently received ALCAR and/or CoQ10 for 5 days. The animals were sacrificed, and the cerebral cortex and cerebellum were collected for analysis. PPA caused histopathological alterations along with increased malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 in the cerebrum and cerebellum of rats. Reduced glutathione (GSH) and antioxidant enzymes were declined in the brain of rats that received PPA. Concurrent treatment with ALCAR and/or CoQ10 prevented tissue injury, decreased MDA, NF-κB p65, and pro-inflammatory cytokines, and enhanced cellular antioxidants in PPA-administered rats. ALCAR and/or CoQ10 upregulated Bcl-2 and decreased Bax and caspase-3 in the brain of rats. In addition, ALCAR and/or CoQ10 upregulated cerebral and cerebellar ALDH1A1 and RARα in PPA-treated rats. The combination of ALCAR and CoQ10 showed more potent effects when compared with the individual treatments. In conclusion, ALCAR and/or CoQ10 prevented tissue injury, ameliorated oxidative stress, inflammatory response, and apoptosis, and upregulated ALDH1A1-RA-RARα signaling in the brain of autistic rats.

Topics: Acetylcarnitine; Animals; Antioxidants; Autism Spectrum Disorder; Inflammation; Neurotoxicity Syndromes; NF-kappa B; Oxidative Stress; Propionates; Rats; Ubiquinone

Propionic acid (PRA) is used as a food preservative. This study was aimed to investigate the neuroprotective effect of acetyl-l-carnitine (ALC) and nano-Coenzyme Q (N-CoQ) on brain intoxication induced by PRA in rats. Rats were divided into five groups: group I: control; group II: received PRA; group III: received ALC; group IV: received N-CoQ; and group V: received ALC and N-CoQ for 5 days. The antioxidants in question markedly ameliorated serum interleukin-1β and tumor necrosis factor-α, and brain NO, lipid peroxide, glutathione, and superoxide dismutase levels as well as protein expression of brain-derived neurotrophic factor (BDNF) and P-cyclic-AMP response element-binding protein (CREB) that were altered by a toxic dose of PRA, as well as histopathological alterations, including improvement of the cerebellum architecture. Interestingly, the combination therapy of ALC and N-CoQ achieved the most neuroprotective effect compared with monotherapies. The current study established that N-CoQ is considered as a useful tool to prevent brain injury induced by PRA. BDNF and CREB proteins are involved in both PRA neurotoxicity and treatment.

Topics: Acetylcarnitine; Animals; Antioxidants; Biomarkers; Brain; Brain-Derived Neurotrophic Factor; Cyclic AMP Response Element-Binding Protein; Food Preservatives; Male; Nanoparticles; Neuroprotective Agents; Oxidative Stress; Propionates; Rats; Signal Transduction; Ubiquinone

Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups.. The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA-treated rats demonstrated in a remarkable amelioration of most of the measured parameters.. In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury, confirmed by improvement in biochemical markers and DNA double strand breaks.

Topics: Animals; Autistic Disorder; Biomarkers; Male; Melatonin; Nerve Tissue Proteins; Neuroprotective Agents; Neurotransmitter Agents; Prognosis; Propionates; Rats; Rats, Wistar; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Ubiquinone