Postnatal baicalin ameliorates behavioral and neurochemical alterations in valproic acid-induced rodent model of autism: The possible implication of sirtuin-1/mitofusin-2/ Bcl-2 pathway.

Autism spectrum disorder (ASD) is characterized by pervasive impairments in social communication along with repetitive or stereotyped behaviors. Although its distinctive etiology isn`t completely understood, genetic and environmental risk factors were incriminated. Being a flavonoid of high biomedical value, baicalin was recently verified as an emerging medicinal herb with numerous pharmacological activities. The objective of this study was to investigate the feasible effects of baicalin on valproic acid (VPA)-induced autism regarding its potential mitochondrial modulatory, antioxidant, and antiapoptotic effects. The present study was performed using a rodent model of autism by exposing rat fetuses to VPA on the 12.5th day of gestation. Ten male Wistar rats that were born from control pregnant females were considered as group I (control group). Twenty male Wistar rats that were born from prenatal VPA- treated females were further divided into two groups: Group II (VPA- induced ASD) and group III (VPA + Baicalin). Postnatal baicalin promoted postnatal growth and maturation. In addition, it improved motor development and ameliorated repetitive behavior as well as social deficits in prenatally exposed VPA rats. Moreover, baicalin enhanced neuronal mitochondrial functions as evidenced by elevation of mitochondrial adenosine triphosphate (ATP) level and promotion of mitofusin-2 expression. Furthermore, baicalin elevated sirtuin-1 (SIRT1) level in VPA rats' brain tissues and restored the antioxidant defense mechanisms. Besides, it abrogated the neuronal histopathological changes in the brain tissues. Based on the data herein, baicalin may provide a promising pre-clinical therapeutic line in ASD as a mitochondrial function modulator, antioxidant and anti-apoptotic agent.

Combination therapy with melatonin, stem cells and extracellular vesicles is effective in limiting renal ischemia-reperfusion injury in a rat model.

OBJECTIVE: To evaluate the therapeutic value of melatonin, mesenchymal stem cells and their extracellular vesicles, exosomes, on renal ischemia-reperfusion. METHODS: Female albino rats (n = 64) were divided into eight groups (n = 8 per group): control, sham (only laparotomy), renal ischemia-reperfusion (renal ischemia-reperfusion + phosphate-buffered saline), melatonin (renal ischemia-reperfusion + melatonin), mesenchymal stem cells (renal ischemia-reperfusion + mesenchymal stem cells), exosomes (renal ischemia-reperfusion + exosomes), melatonin + mesenchymal stem cells (renal ischemia-reperfusion + melatonin + mesenchymal stem cells) and melatonin + exosomes (renal ischemia-reperfusion + melatonin + exosomes). After the establishment of the renal ischemia-reperfusion model, rats in each group were bilaterally injected once with either mesenchymal stem cells or exosomes in both renal arteries during reperfusion. RESULTS: Notable improvement of renal ischemia-reperfusion was obtained after different treatments, as evidenced by a lower histopathological score of kidney injury; decreased serum levels of urea, creatinine and retinol-binding protein; reduced lipid peroxidation marker malondialdehyde; increased superoxide dismutase and catalase activities; reduced apoptosis (lower DNA damage and B-cell lymphoma 2-associated X protein, and higher B-cell lymphoma 2 genes/proteins); and inhibition of kidney inflammatory and damage markers (tumor necrosis alpha, interleukin-1ß, nuclear factor kappa B, kidney injury molecule-1, IL-18, matrix metalloproteinase 9, neutrophil gelatinase-associated lipocalin). The improvement order was (highest to lowest): melatonin + exosomes, melatonin + mesenchymal stem cells, exosomes, mesenchymal stem cells and melatonin group. CONCLUSIONS: Our data suggest a potential therapeutic effect of combined therapy with melatonin, mesenchymal stem cells and their exosomes to minimize renal ischemia-reperfusion injury in rats.