Sulforaphane mitigates behavioral deficits in experimental chronic kidney disease through regulation of Nrf2/NLRP3 inflammasome.

Depression is one of the most prevalent psychiatric disorders among patients with chronic kidney disease (CKD). Growing evidence suggests that oxidative stress and inflammation contribute to the development of CKD-associated depression. Sulforaphane, a natural isothiocyanate with potent antioxidant and anti-inflammatory properties, has demonstrated promising neuroprotective and antidepressant-like effects. Therefore, this study investigated the effects of sulforaphane on depressive-like behavior in an adenine-induced CKD rat model and explored the underlying mechanisms, using fluoxetine as a reference treatment. Forty adult male Wistar rats were randomly assigned to five equal groups. Group I (control) received the drug vehicle, Group II received an adenine-containing diet (0.25% w/w in feed), Group III received an adenine-containing diet plus oral sulforaphane (5 mg/kg/day), Group IV received an adenine-containing diet plus oral sulforaphane (0.5 mg/kg/day), and Group V received an adenine-containing diet plus oral fluoxetine (10 mg/kg/day). The experimental period lasted for 5 weeks. Behavioral assessments were conducted during the final week using the sucrose preference, light-dark, and forced swim tests. Following euthanasia, kidney and brain tissues were collected for biochemical and histopathological analyses. Brain oxidative stress markers, including malondialdehyde (MDA), reduced glutathione (GSH), and nuclear factor erythroid 2-related factor 2 (Nrf2), as well as inflammatory markers, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and NOD-like receptor protein 3 (NLRP3) inflammasome, were evaluated. Sulforaphane dose-dependently improved renal function, histopathological alterations, behavioral performance, and brain antioxidant and anti-inflammatory status. These beneficial effects may be associated, at least in part, with modulation of the Nrf2/NLRP3 signaling pathway.