Effects of silymarin on angiogenesis and oxidative stress in streptozotocin-induced diabetes in mice

• Published in: Biomedicine & pharmacotherapy 2018-12, Vol.108, p.232-243
• Main Authors: Stolf, Aline Maria, Campos Cardoso, Cibele, Morais, Helen de, Alves de Souza, Carlos Eduardo, Lomba, Luís Alexandre, Brandt, Anna Paula, Agnes, Jonathan Paulo, Collere, Flávia Caroline, Galindo, Claudia Martins, Corso, Claudia Rita, Spercoski, Katherinne Maria, Locatelli Dittrich, Rosangela, Zampronio, Aleksander Roberto, Cadena, Silvia Maria Suter Correia, Acco, Alexandra
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Blood Vessels - drug effects; Blood Vessels - pathology; Body Weight - drug effects; Collagen - metabolism; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - pathology; Free Radical Scavengers - pharmacology; Hyperglycemia - blood; Hyperglycemia - complications; Inflammation; Inflammation - pathology; Kidney - drug effects; Kidney - pathology; Liver - drug effects; Liver - pathology; Male; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Neovascularization, Physiologic - drug effects; Oxidative stress; Oxidative Stress - drug effects; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; Silymarin; Silymarin - pharmacology; Silymarin - therapeutic use; Streptozotocin
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.09.042

•Diabetes led to impairments of antioxidant defenses in pancreas, liver and kidneys.•Diabetes lowered the number of vessels in the implanted sponge model in mice.•Silymarin improved the antioxidant defenses and attenuated the inflammatory process.•Silymarin had benefits without apparent toxicity.•Silymarin may be a promising drug for controlling diabetic complications. The present study evaluated the effects of acute treatment with silymarin, an extract that is obtained from Silybum marianum, on angiogenesis, oxidative stress, and inflammation in normoglycemic and diabetic mice. Diabetes was induced by streptozotocin (80 mg/kg, intraperitoneal) in male Swiss mice, 6 weeks of age. A polyether-polyurethane sponge was surgically implanted in the back of the mice as a model of healing in both diabetic and normoglycemic animals that were treated with oral silymarin or water for 10 days. The pancreas, liver, kidneys, blood, and sponges were collected and analyzed. Diabetes led to impairments of antioxidant defenses, reflected by a reduction of pancreatic superoxide dismutase and hepatic and renal catalase and an increase in pancreatic lipoperoxidation. An inflammatory process was observed in diabetic mice, reflected by an increase in pancreatic tumor necrosis factor α (TNF-α) and the infiltration of inflammatory cells in islets. The number of vessels was lower in the implanted sponges in diabetic mice. Silymarin treatment attenuated this damage, restoring antioxidant enzymes and reducing pancreatic TNF-α and inflammatory infiltration. However, silymarin treatment did not restore angiogenesis or glycemia. In conclusion, treatment with silymarin red uced oxidative stress and inflammation that were induced in the model of streptozotocin-induced diabetes in several organs, without apparent toxicity. Silymarin may be a promising drug for controlling diabetic complications.