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

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Dipartimento di Farmacologia, Chemioterapia e Tossicologia medica, Università degli Studi di Milano, via Vanvitelli 32, 20129 Milano, Italy.

    , , , ,

    Source

    European journal of pharmacology 650:2-3 2011 Jan 15 pg 694-702

    MeSH

    Animals
    Anti-Inflammatory Agents
    Antioxidants
    Aorta, Thoracic
    Brain
    Cytokines
    Diabetes Mellitus, Experimental
    Diabetic Neuropathies
    Genistein
    Hyperalgesia
    Hyperglycemia
    Inflammation
    Liver
    Male
    Mice
    Mice, Inbred C57BL
    Nerve Growth Factors
    Nitric Oxide Synthase Type II
    Nitric Oxide Synthase Type III
    Oxidative Stress
    Reactive Oxygen Species
    Sciatic Nerve
    Superoxide Dismutase

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    21050844

    Citation

    Valsecchi, Anna Elisa, et al. "The Soy Isoflavone Genistein Reverses Oxidative and Inflammatory State, Neuropathic Pain, Neurotrophic and Vasculature Deficits in Diabetes Mouse Model." European Journal of Pharmacology, vol. 650, no. 2-3, 2011, pp. 694-702.
    Valsecchi AE, Franchi S, Panerai AE, et al. The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model. Eur J Pharmacol. 2011;650(2-3):694-702.
    Valsecchi, A. E., Franchi, S., Panerai, A. E., Rossi, A., Sacerdote, P., & Colleoni, M. (2011). The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model. European Journal of Pharmacology, 650(2-3), pp. 694-702. doi:10.1016/j.ejphar.2010.10.060.
    Valsecchi AE, et al. The Soy Isoflavone Genistein Reverses Oxidative and Inflammatory State, Neuropathic Pain, Neurotrophic and Vasculature Deficits in Diabetes Mouse Model. Eur J Pharmacol. 2011 Jan 15;650(2-3):694-702. PubMed PMID: 21050844.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model. AU - Valsecchi,Anna Elisa, AU - Franchi,Silvia, AU - Panerai,Alberto Emilio, AU - Rossi,Alice, AU - Sacerdote,Paola, AU - Colleoni,Mariapia, Y1 - 2010/11/02/ PY - 2010/09/21/received PY - 2010/10/26/accepted PY - 2010/11/6/entrez PY - 2010/11/6/pubmed PY - 2011/5/3/medline SP - 694 EP - 702 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 650 IS - 2-3 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/21050844/The_soy_isoflavone_genistein_reverses_oxidative_and_inflammatory_state_neuropathic_pain_neurotrophic_and_vasculature_deficits_in_diabetes_mouse_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(10)01087-3 DB - PRIME DP - Unbound Medicine ER -