The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model

• Published in: European journal of pharmacology 2011-01, Vol.650 (2), p.694-702
• Main Authors: Valsecchi, Anna Elisa, Franchi, Silvia, Panerai, Alberto Emilio, Rossi, Alice, Sacerdote, Paola, Colleoni, Mariapia
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Biological and medical sciences; brain; Brain - drug effects; Brain - metabolism; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Cytokines; Cytokines - metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; diabetic complications; Diabetic Neuropathies - complications; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - physiopathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; endothelial nitric oxide synthase; enzyme activity; enzyme-linked immunosorbent assay; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Filaments; fluorometry; Genistein; Genistein - pharmacology; Genistein - therapeutic use; glutathione; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; hyperglycemia; Hyperglycemia - complications; Hyperglycemia - drug therapy; Hypersensitivity; Immunoblotting; inducible nitric oxide synthase; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - physiopathology; Isoflavones; liver; Liver - drug effects; Liver - metabolism; Male; malondialdehyde; Medical sciences; Mice; Mice, Inbred C57BL; Nerve growth factor; Nerve Growth Factors - metabolism; nerve tissue; Nervous system (semeiology, syndromes); Neurology; Neuropathy; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Oxidative stress; Oxidative Stress - drug effects; pain; Pain perception; peripheral nervous system diseases; pharmacology; Pharmacology. Drug treatments; protein content; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sciatic nerve; Sciatic Nerve - drug effects; Sciatic Nerve - metabolism; Soybeans; streptozotocin; superoxide dismutase; Superoxide Dismutase - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.10.060

Treatment of diabetes complications remains a substantial challenge. The aim of this study was to explore the ability of the soy isoflavone genistein in attenuating the signs that follow diabetes onset: nociceptive hypersensitivity, oxidative and inflammatory state, nerve growth factor (NGF) decrease and vascular dysfunctions. Genistein (3 and 6 mg/kg) was administered to C57BL/6J streptozotocin diabetic mice from the 2nd till the 5th week after disease induction. The hind paw withdrawal threshold to mechanical stimulation (tactile allodynia) was evaluated by a von Frey filament. The oxidative stress was assessed measuring: reactive oxygen species by fluorimetric analysis, both the lipoperoxide content, as malondialdehyde, the antioxidant enzymatic activities spectrophotometrically and the glutathione content spectrofluorimetrically. Proinflammatory cytokines and NGF were measured in the sciatic nerve by enzyme-linked immunosorbent assay. Aortic inducible (iNOS) and endothelial nitric oxide synthase (eNOS) protein content was measured by western immunoblotting. Genistein relieved diabetic peripheral painful neuropathy, reverted the proinflammatory cytokine and reactive oxygen species overproduction, and restored the NGF content in diabetic sciatic nerve. Furthermore it restored the GSH content and the GSH and GSSG ratio, improved the antioxidant enzymes activities, decreased reactive oxygen species and lipoperoxide level in the brain and liver. Finally it restored the iNOS and eNOS content and the superoxide dismutase activity in thoracic aorta. Hyperglycaemia and weight decrease were not affected. Genistein is able to reverse a diabetes established condition of allodynia, oxidative stress and inflammation, ameliorates NGF content and the vascular dysfunction, thus suggesting its possible therapeutic use for diabetes complications.