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.

Antineoplastic effect of pectic polysaccharides from green sweet pepper (Capsicum annuum) on mammary tumor cells in vivo and in vitro.

The present study investigated the antineoplastic effects of pectic polysaccharides that were extracted from green sweet pepper (Capsicum annuum [CAP]) in the Ehrlich carcinoma in mice and in human mammary tumor lineages. After the subcutaneous inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice received 50, 100, or 150 mg/kg CAP or vehicle orally once daily or methotrexate (2.5 mg/kg, i.p., every 5 days) for 21 days. CAP dose-dependently reduced Ehrlich tumor growth. It also reduced the viability of MCF-7, MDA-MB-231, and MDA-MB-436 human mammary cell lineages. Treatment with CAP reduced the gene expression of vascular endothelial growth factor in vivo and in vitro, reduced vessel areas of the tumors, and induced necrosis in Ehrlich solid tumors. CAP treatment significantly increased Interleukin-6 in tumors. The antineoplastic effect of CAP appears to depend on the regulation of inflammation and angiogenesis. Further studies are encouraged to better understand the CAP potential for the treatment of breast tumors.

Ruthenium complex exerts antineoplastic effects that are mediated by oxidative stress without inducing toxicity in Walker-256 tumor-bearing rats.

The present study evaluated the in vivo antitumor effects and toxicity of a new Ru(II) compound, cis-(Ru[phen]2[ImH]2)2+ (also called RuphenImH [RuC]), against Walker-256 carcinosarcoma in rats. After subcutaneous inoculation of Walker-256 cells in the right pelvic limb, male Wistar rats received 5 or 10mgkg-1 RuC orally or intraperitoneally (i.p.) every 3 days for 13 days. A positive control group (2mgkg-1 cisplatin) and negative control group (vehicle) were also used. Tumor progression was checked daily. After treatment, tumor weight, plasma biochemistry, hematology, oxidative stress, histology, and tumor cell respiration were evaluated. RuC was effective against tumors when administered i.p. but not orally. The highest i.p. dose of RuC (10mgkg-1) significantly reduced tumor volume and weight, induced oxidative stress in tumor tissue, reduced the respiration of tumor cells, and induced necrosis but did not induce apoptosis in the tumor. No clinical signs of toxicity or death were observed in tumor-bearing or healthy rats that were treated with RuC. These results suggest that RuC has antitumor activity through the modulation of oxidative stress and impairment of oxidative phosphorylation, thus promoting Walker-256 cell death without causing systemic toxicity. These effects make RuC a promising anticancer drug for clinical evaluation.