A single intranasal dose of adipose tissue-derived MSC secretome inhibited ethanol and nicotine intake and reduced the hippocampal oxidative stress (assessed by GSSG/GSH ratio) induced by chronic ethanol or nicotine intake. The hippocampi were extracted from rats chronically drinking alcohol or nicotine solutions 24 h a day, without deprivation periods. a Intranasal administration of one dose of MSC-derived secretome inhibited (85%) chronic ethanol intake within 48 h after the administration (two-tailed Student t test = 10.04, p < 0.001). b A single intranasal dose of MSC-derived secretome inhibited (75%) chronic nicotine intake (two-tailed Student t test = 5.06, p < 0.001) within 48 h after secretome administration. c Chronic ethanol-drinking rats treated with vehicle displayed an increased GSSG/GSH ratio (red bar) versus ethanol-naïve rats drinking only water (black bar). A single intranasal dose of secretome administered to ethanol drinking rats resulted in a full normalization of the GSSG/GSH ratio (blue bar) (one-way ANOVA: F2,9 = 8.0, p < 0.01; Bonferroni post-hoc: p < 0.01, water drinking versus ethanol-vehicle; p < 0.02, ethanol-secretome versus ethanol-vehicle; n = 5 per group). d Chronic nicotine-drinking rats treated with vehicle displayed an increased GSSG/GSH ratio (red bar) versus naïve rats drinking only water (black bar). A single intranasal dose of secretome administered to nicotine-drinking rats resulted in a full normalization of the GSSG/GSH ratio (blue bar, one-way ANOVA: F2,9 = 34.0, p < 0.0001; Bonferroni post-hoc: p < 0.01, water drinking versus ethanol-vehicle; p < 0.02, ethanol-secretome versus ethanol-vehicle; n = 5 per group)