Bixin attenuates mechanical allodynia, anxious and depressive-like behaviors associated with experimental diabetes counteracting oxidative stress and glycated hemoglobin.

Neuropathic pain, depression, and anxiety are common comorbidities in diabetic patients, whose pathophysiology involves hyperglycemia-induced increased oxidative stress. Bixin (BIX), an apocarotenoid extracted from the seeds of Bixa orellana, has been used in traditional medicine to treat diabetes and has been recognized by its antioxidant profile. We aimed to investigate the effect of the BIX over the mechanical allodynia, depressive, and anxious-like behaviors associated with experimental diabetes, along with its involved mechanisms. Streptozotocin-induced diabetic rats were treated for 17 days (starting 14 days after diabetes induction) with the corresponding vehicle, BIX (10, 30 or 90 mg/kg; p.o), or INS (6 IU; s.c.). Mechanical allodynia, depressive, and anxious-like behavior were assessed by electronic Von Frey, forced swimming, and elevated plus-maze tests, respectively. Locomotor activity was assessed by the open field test. Blood glycated hemoglobin (HbA1) and the levels of lipid peroxidation (LPO) and reduced glutathione (GSH) were evaluated on the hippocampus, pre-frontal cortex, lumbar spinal cord, and sciatic nerve. Diabetic animals developed mechanical allodynia, depressive and anxious-like behavior, increased plasma HbA1, increased LPO, and decreased GSH levels in tissues analyzed. Repeated BIX-treatment (at all tested doses) significantly attenuated mechanical allodynia, the depressive (30 and 90 mg/kg) and, anxious-like behaviors (all doses) in diabetic rats, without changing the locomotor performance. BIX (at all tested doses) restored the oxidative parameters in tissues analyzed and reduced the plasma HbA1. Thereby, bixin may represent an alternative for the treatment of comorbidities associated with diabetes, counteracting oxidative stress and plasma HbA1.