<b><i>Introduction:</i></b> The leading cause of memory impairment is dementia-related disorders. Since current treatments for memory impairment target the neuroinflammatory pathways, we selected dapsone, an anti-inflammatory agent, to evaluate its effects on scopolamine-induced memory impairment in mice and the underlying role of nitric oxide (NO). <b><i>Methods:</i></b> Scopolamine (1 mg/kg, intraperitoneal [i.p.]) was used for induction of memory impairment. The animals received various doses of dapsone (0.1, 0.3, 1, 5, and 10 mg/kg, i.p.). Duration and number of arms visits in the Y-maze and step-through latency in the passive-avoidance were documented. To evaluate the underlying signaling pathway, N(ω)-nitro-L-arginine methyl ester (a nonspecific NO synthase [NOS] inhibitor), aminoguanidine (a specific inducible NOS inhibitor), and 7-nitroindazole (a specific neuronal NOS inhibitor) were administered 30 min after dapsone administration. <b><i>Results:</i></b> Dapsone (5 mg/kg) substantially improved memory acquisition in scopolamine-induced memory impairment. Additionally, NOS inhibitors considerably reversed the observed neuroprotective effects of dapsone, accompanied by the elevation of NO levels. <b><i>Conclusion:</i></b> Dapsone revealed a neuroprotective effect against scopolamine-induced memory impairment in mice, possibly through the nitrergic pathway.
Background One of the major complications associated with random-pattern skin flaps is distal necrosis. Cannabidiol (CBD) has recently gained much attention as a therapeutic anti-inflammatory agent. We aimed to evaluate the efficacy of CBD on the random-pattern skin flap survival (SFS) in rats and to explore the possible involvement of cannabinoid type-2 (CB2) receptors.
Methods In this controlled experimental study, we randomly divided male Wistar rats into seven study groups (six rats each). We performed a random-pattern skin flap model in each rat following pretreatment with vehicle (control) or multiple doses of CBD (0.3, 1, 5, or 10 mg/kg). In a separate group, we injected SR144528 (2 mg/kg), a high affinity and selective CB2 inverse agonist, before the most effective dose of CBD (1 mg/kg). A sham nontreated and nonoperated group was also included. Seven days after surgeries, the percentage of necrotic area (PNA) was calculated. Histopathological microscopy, CB2 expression level, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α concentrations were also investigated in the flap tissue samples.
Results A PNA of 72.7 ± 7.5 (95% confidence interval [CI]: 64.8–80.6) was captured in the control group. Following treatment with CBD 0.3, 1, 5, and 10 mg/kg, a dose-dependent effect was observed with PNAs of 51.0 ± 10.0 (95% CI: 40.5–61.5; p <0.05), 15.4 ± 5.8 (95% CI: 9.3–21.5; p <0.001), 37.1 ± 10.2 (95% CI: 26.3–47.8; p <0.001), and 46.4 ± 14.0 (95% CI: 31.7–61.1; p <0.001), respectively. Histopathologically, tissues enhanced significantly. Besides, CB2 expression surged remarkably, IL-1β and TNF-α concentrations decreased considerably after treatment with CBD of 1 mg/kg compared with the control (p <0.05 and <0.001, respectively). Administering SR144528 reversed the favorable effects of CBD of 1 mg/kg, both macroscopically and microscopically.
Conclusion Pretreatment with CBD of 1 mg/kg improved SFS considerably in rats and exerted desirable anti-inflammatory effects which were possibly mediated by CB2 receptors.
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