RESUMO
Autism is a neurodevelopmental disorder. A variety of molecular and cellular abnormalities leads to behavioral deficits in autism. Nevertheless, its etiology and treatment strategy are not completely understood. Oxytocin has recently shown improvements in social functioning. This study aimed to evaluate the necroptosis pathway for the neuroprotective effects of oxytocin in the valproic acid-induced autism spectrum disorder model. The autism spectrum disorder was induced by valproic acid on gestational day 12.5 (600 mg/kg, intraperitoneally). Offspring received intranasal oxytocin (1 µg/µL) on the 21st and 40th days after birth. The offspring behaviors were scrutinized by self-grooming, marble-burying, three-chamber, and Morris water maze tests. Western blot was performed on the hippocampus and amygdala tissues to investigate the expression of RIP3 and MLKL markers. The valproic acid group demonstrated more anxiety, repetitive behaviors, and expression of RIP3 and MLKL markers, and less social interaction and spatial memory compared with the control group. Oxytocin considerably improved social interactions, preference for social novelty, and memory. The elevated expression of RIP3 and MLKL markers in valproic acid-induced autistic rats were alleviated after treatment with oxytocin. We also highlighted the importance of age and gender in autism spectrum disorder interventions. Our findings suggested that oxytocin administration was as an effective treatment in two areas of repetitive/stereotyped behaviors, social interactions/cognitive function. Notably, early administration of oxytocin resulted in better therapeutic responses in autism-like behaviors. The molecular tests introduce oxytocin as a potential candidate for reducing the expression of necroptosis mediators in the brain. This reinforced our hypothesis that the necroptosis pathway takes part in autism spectrum disorder.
RESUMO
Mitochondrial oxidative damage is a crucial factor in the pathogenesis of diabetic nephropathy (DN), which is among the most prevalent problems of diabetes, and there hasn't been an effective treatment for DN yet. This study planned to investigate the effects of Salvia spinosa L. on mitochondrial function along with its protection against streptozotocin-induced nephropathy in diabetic mice. After the injection of streptozotocin (STZ) and verification of the establishment of diabetes, mice (n = 30) were randomly divided into the following groups: control group, diabetic-control, S. spinosa-treated diabetic (50, 100, and 200 mg/kg), and metformin-treated diabetic group (500 mg/kg). After four weeks of treatment, the mice were weighed. Blood and kidney tissues were examined for biochemical and histological evaluation. Hematoxylin and eosin staining was used for evaluating renal pathologic damage. Oxidative damage in the kidney was assessed by the evaluation of lipid peroxidation and glutathione oxidation. Furthermore, differential centrifugation was used to obtain the isolated mitochondria, and mitochondrial toxicity endpoints (mitochondrial function and mitochondrial oxidative markers) were determined in them. S. spinosa remarkably reduced the blood urea and creatinine concentrations, and also normalized kidney weight/body weight coefficient in the diabetic mice. S. spinosa ameliorated the incidence of glomerular and tubular pathological changes in histological analyses. Moreover, the oxidative and mitochondrial damages were notably attenuated in renal tissues of S. spinosa-treated mice. These results indicate that the methanolic extract of S. spinosa modulates the nephropathy in the diabetic mice by the amelioration of oxidatively induced mitochondrial damage and provides a reliable scientific base, suggesting S. spinosa as a promising alternative remedy against DN.