Hydrogen Sulfide Attenuates the Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.

Abstract

Fetal alcohol spectrum disorder (FASD), which is caused by prenatal alcohol exposure, can result in cell death in specific brain regions. Alcohol-induced neurocognitive defects offspring's are included with activation of oxidative-inflammatory cascade followed with wide apoptotic neurodegeneration in many brain's regions such as hippocampus. According to the latest studies, H2S (hydrogen sulfide) can protect neuronal cells via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms in different animal models. Therefore, we aimed to evaluate the protective effects of H2S on ethanol-induced neuroinflammation and neuronal apoptosis in pup hippocampus with postnatal alcohol exposure. Administration of ethanol (5.27g/kg) in milk solution (27.8mL/kg) for each rat pups was performed through intragastric intubation on 2 to 10 postnatal days and NaHS as H2S donor (1mg/kg) was injected on similar time, subcutaneously. For examining the antioxidant and anti-inflammatory effects, ELISA assay was performed to determine the levels of TNF-α, IL1β, and antioxidant enzymes. Immunohistochemical staining was performed to evaluate the expression levels of GFAP and caspase-3 also Nissl staining was done for necrotic cell death evaluation. H2S treatment could significantly increase the activity of total superoxide dismutase, catalase, and glutathione (P < 0.05). It also decreased the levels of TNF-α, IL1β, and malondialdehyde, compared with the ethanol group (P < 0.05). Moreover, the number of hippocampal caspase-3, GFAP-positive cells, and necrotic cells death reduced in the H2S group (P< 0.01). Based on the findings, H2S can inhibit apoptotic signaling that is mediated by the oxidative-inflammatory cascade following ethanol exposure of rat pups on postnatal period.