RESUMEN
BACKGROUND: Diabetic nephropathy can lead to renal diseases; oxidative stress and mitochondrial dysfunction have critical roles in its development. OBJECTIVES: In this study, the effect of syringic acid (SYR), a natural phenolic acid, on diabetic nephropathy and mitochondrial biogenesis was 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 activities 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. SYR significantly reduced the 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 the non-treated diabetic group. The results show improvement of histopathological damages of kidney in the 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.
Asunto(s)
Antioxidantes/farmacología , Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Ácido Gálico/análogos & derivados , Animales , Antioxidantes/uso terapéutico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/patología , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Biogénesis de Organelos , Estrés Oxidativo/efectos de los fármacos , RatasRESUMEN
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.
