Diabetes is a metabolic complaint associated with oxidative stress and dysfunction of mitochondria. One of the most common complications of diabetes mellitus is neuropathy. This study evaluated the possible neuroprotective effects of syringic acid (SYR), a natural polyphenolic derivative of benzoic acid, on oxidative damage and mitochondria in the brain, spinal cord, and sciatic nerve of streptozotocin-induced diabetic rats. Different groups of rats including normal control, diabetics (induced by streptozotocin), diabetic groups treated with 25, 50, and 100 mg/kg of SYR, and non-diabetic group treated with only 100 mg/kg of SYR were treated for 6 weeks. Learning and memory function, physical coordination, and acetylcholinesterase (AChE) and antioxidant indexes, as well as mRNA expression of mitochondrial biogenesis, were measured in the brain, spinal cord, and sciatic nerves. Diabetic rats treated with 100 mg/kg SYR exhibited significantly improved learning, memory, and movement deficiency ( p < 0.05 ). SYR 100 mg/kg also significantly upregulated the brain mRNA expression of PGC-1α and NRF-1, the key regulators of energy metabolism, oxidative phosphorylation, and mitochondrial biogenesis. In addition, SYR 100 mg/kg and SYR 50 mg/kg increased the mtDNA/nDNA ratio in the brain and the spinal cord of diabetic rats, respectively ( p < 0.05 ). SYR attenuated the lipid peroxidation in all the tissues, but not significant effects were observed on GSH, AChE, catalase, and superoxide dismutase activity. In all the tests, nonsignificant differences were observed between the control and SYR 100 mg/kg groups. Moreover, SYR reduced inflammation and demyelination in sciatic nerves. This is the first study to reveal the regulation of mitochondrial biogenesis and energy metabolism by SYR, beyond its antioxidant role in the diabetic rats’ brain and spinal tissues.
Background: Diabetic nephropathy can lead to renal diseases, and oxidative stress and mitochondrial dysfunction have critical roles in its development. Objectives: In this study, the effect of syringic acid (SYR), natural phenolic acid on diabetic nephropathy and mitochondrial biogenesis were examined. Methods: Diabetes was induced in rats by injecting streptozotocin. SYR (25, 50 and 100 mg/kg/day) was orally administered for 6 weeks. SYR effects on factors, such as antioxidant activity and mRNA expression level of mitochondrial biogenesis indexes were evaluated. Results: In SYR-treated rats, blood glucose and ALP level were significantly reduced. SYR increased kidney GSH content in the diabetic group. Elevated renal catalase and superoxide dismutase activities in diabetic rats were restored to normal levels after treatment. The SYR significantly reduced renal TBARS level, which had increased in diabetic rats. This compound also significantly upregulated renal mRNA expression of PGC-1α and NRF-1, and increased mtDNA/nDNA ratio in diabetic rats. These values were reduced in non-treated diabetic group. The result show improvement of histopathological damages of kidney in SYR treated group in comparison with the diabetic group. Conclusion: According to the results, SYR alters renal antioxidant defense mechanisms. Also, it could be considered as a novel approach by targeting mitochondria in renal diabetic complications.
This Project was performed to provide an in vitro Point of Departure (PoD) for an Adverse Outcome Pathway (AOP)‐informed Integrated Approach to Testing and Assessment (IATA), concerning a potential risk of parkinsonian motor deficits after long‐term exposure to Tebufenpyrad. The AOP considered was AOP:3. Assays were performed for Key Event (KE) 1, KE2 (mitochondrial dysfunction) and KE4 of the AOP, based on the use of human dopaminergic neurons (LUHMES cells). KE1 (inhibition of complex I of the mitochondrial respiratory chain) was considered equivalent to the molecular initiating event (MIE). KE4 (dopaminergic cell degeneration) was considered as alternative AO (target cell degeneration). All necessary and linear steps of the AOP (i.e. KE2,3,4) were investigated by experimental test methods. The three major objectives were: (i) generation of potential PoD data from each assay; (ii) evaluation and optimization of the consistency of these data; (iii) selection of a PoD to be used for further risk assessment. During the optimization phase, assay conditions that reflect brain metabolism (MitoMet conditions) were implemented, and degeneration of neurites was considered the most relevant neuropathological endpoint. With this setting, the potential PoD ranged from 6 nM to 45 nM. The selection of the PoD put emphasis on more chronic effects and on the assay closest to the AO. Thus the KE4 assay, measuring neurite degeneration under MitoMet conditions was chosen, and the PoD was 8 nM. This value has a confidence interval of about one log10‐fold change from the lowest to the highest estimate (range: 3 nM – 30 nM), based on the experimental variations we observed. Some biokinetics measurements were undertaken to help estimating cell concentrations. These data had a high uncertainty concerning the measurements and the model assumptions. Based on the assumptions we consider most realistic and robust, we suggest a cell/tissue (brain) concentration of 8‐40 nM to be associated with a potential onset of toxicity of Tebufenpyrad.
Background: Sodium benzoate, a food preservative, prevents the growth of fungi and bacteria. Numerous studies have reported the protective effects of sodium benzoate on the nervous system. This study investigated the effect of sodium benzoate on cell apoptosis and mitochondrial function in an aluminum cell toxicity model. Methods: After 48 hr of treating PC-12 cells with varying concentrations of sodium benzoate (0.125, 0.25 or 0.5 mg/ml) in the presence of aluminum maltolate (500 μM), the cell viability was assessed by MTT assay. The type of cell death (necrosis or apoptosis) was analyzed by flow cytometry (7-ADD/An V-PE staining). Also, rhodamine 123 was used to measure the Mitochondrial Membrane Potential (MMP). The acetylcholinesterase activity (AChE) was assessed by Ellman’s method. Results: It was observed that sodium benzoate inhibited aluminum induced cell death within 48hr. Sodium benzoate at a concentration of 0.5 mg/ml significantly reduced the apoptotic cells that had been exposed to aluminum. Exposure of PC-12 cells with sodium benzoate and aluminum, increased the AChE activity, although, no significant changes in mitochondrial membrane potential were observed. Conclusion: Sodium benzoate may provide its protective effects through increased AChE activity and inhibiting apoptosis induced by aluminum toxicity. It is likely that the disruption of MMP is neither involved in the induction of apoptosis by aluminum nor in the protective effect of sodium benzoate.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.