Enhancing mood post-bariatric surgery: Associations of rosuvastatin with vitamin D, oxidative stress, and neurotransmitter-related outcomes in rats

Bariatric surgery is effective for severe obesity, yet post-surgical depression poses challenges to weight loss outcomes. Beyond lipid-lowering, statins reduce diabetes recurrence and cardiac risks. Statin use has been linked with higher vitamin D levels, which decline after surgery. Rosuvastatin shows neuroprotective associations and potential benefits in reducing depression. Therefore, the aim of our study is to investigate the role of rosuvastatin in post-bariatric surgery depression. Twenty-four male Wistar rats were divided into four groups: Sham, which underwent a sham operation and received normal saline for 4 months, Sham + Rosuvastatin (2 mg/kg, orally), Gastric Banding, and Gastric Banding + Rosuvastatin, which received rosuvastatin post-surgery for 4 months. Body weight, lipid profile, and depressive-like behavior were assessed. Hippocampal levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT), dopamine (DA), and noradrenaline (NA) were measured, along with antioxidant markers including catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Serum levels of 1,25-dihydroxyvitamin D and its transporter SR-B1 were analyzed, as well as gene expression levels of the vitamin D catabolic enzyme CYP24A1 and activating enzyme CYP27B1 were also examined. Rosuvastatin treatment was associated with improvements in depressive-like behavior, reductions in oxidative stress, and normalization of neurotransmitter levels. Rosuvastatin treatment was associated with higher levels of vitamin D, CYP27B1, and SR-B1, along with lower levels of CYP24A1. The findings represent a preliminary study suggesting that rosuvastatin may be a potential therapeutic option for post-gastric banding–associated depressive-like behavior.