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Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in experimental diabetic neuropathy.

Abstract

Oxidative stress has been implicated to play an important role in the pathogenesis of diabetic neuropathy, which is the most common complication of diabetes mellitus affecting more than 50% of diabetic patients. In the present study, we have investigated the effect of U83836E [(-)-2-((4-(2,6-Di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl)methyl)-3,4-dihydro-2,3,7,8-tetramethyl-2H-1-benzopyran-6-ol, 2HCl], a potent free radical scavenger in streptozotocin (STZ)-induced diabetic neuropathy in rats. STZ-induced diabetic rats showed significant deficit in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and thermal hyperalgesia after 8 weeks of diabetes induction, indicating development of diabetic neuropathy. Antioxidant enzyme (superoxide dismutase and catalase) levels were reduced and malondialdehyde (MDA) levels were significantly increased in diabetic rats as compared to the age-matched control rats, this indicates the involvement of oxidative stress in diabetic neuropathy. The 2-week treatment with U83836E (3 and 9 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, hyperalgesia, MDA levels and antioxidant enzymes in diabetic rats. Results of the present study suggest the potential of U83836E in treatment of diabetic neuropathy.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sec-67, S.A.S. Nagar (Mohali), Punjab-160062, India.

    ,

    Source

    Life sciences 79:8 2006 Jul 17 pg 777-83

    MeSH

    Animals
    Antioxidants
    Blood Glucose
    Body Weight
    Catalase
    Chromans
    Diabetes Mellitus, Experimental
    Diabetic Neuropathies
    Hyperalgesia
    Lipid Peroxidation
    Male
    Neural Conduction
    Oxidative Stress
    Piperazines
    Rats
    Rats, Sprague-Dawley
    Regional Blood Flow
    Sciatic Nerve
    Superoxide Dismutase

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16581090

    Citation

    Sayyed, Sufyan G., et al. "Effects of U83836E On Nerve Functions, Hyperalgesia and Oxidative Stress in Experimental Diabetic Neuropathy." Life Sciences, vol. 79, no. 8, 2006, pp. 777-83.
    Sayyed SG, Kumar A, Sharma SS. Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in experimental diabetic neuropathy. Life Sci. 2006;79(8):777-83.
    Sayyed, S. G., Kumar, A., & Sharma, S. S. (2006). Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in experimental diabetic neuropathy. Life Sciences, 79(8), pp. 777-83.
    Sayyed SG, Kumar A, Sharma SS. Effects of U83836E On Nerve Functions, Hyperalgesia and Oxidative Stress in Experimental Diabetic Neuropathy. Life Sci. 2006 Jul 17;79(8):777-83. PubMed PMID: 16581090.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in experimental diabetic neuropathy. AU - Sayyed,Sufyan G, AU - Kumar,Ashutosh, AU - Sharma,Shyam S, Y1 - 2006/03/31/ PY - 2005/08/05/received PY - 2006/02/17/revised PY - 2006/02/22/accepted PY - 2006/4/4/pubmed PY - 2006/8/17/medline PY - 2006/4/4/entrez SP - 777 EP - 83 JF - Life sciences JO - Life Sci. VL - 79 IS - 8 N2 - Oxidative stress has been implicated to play an important role in the pathogenesis of diabetic neuropathy, which is the most common complication of diabetes mellitus affecting more than 50% of diabetic patients. In the present study, we have investigated the effect of U83836E [(-)-2-((4-(2,6-Di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl)methyl)-3,4-dihydro-2,3,7,8-tetramethyl-2H-1-benzopyran-6-ol, 2HCl], a potent free radical scavenger in streptozotocin (STZ)-induced diabetic neuropathy in rats. STZ-induced diabetic rats showed significant deficit in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and thermal hyperalgesia after 8 weeks of diabetes induction, indicating development of diabetic neuropathy. Antioxidant enzyme (superoxide dismutase and catalase) levels were reduced and malondialdehyde (MDA) levels were significantly increased in diabetic rats as compared to the age-matched control rats, this indicates the involvement of oxidative stress in diabetic neuropathy. The 2-week treatment with U83836E (3 and 9 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, hyperalgesia, MDA levels and antioxidant enzymes in diabetic rats. Results of the present study suggest the potential of U83836E in treatment of diabetic neuropathy. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/16581090/Effects_of_U83836E_on_nerve_functions_hyperalgesia_and_oxidative_stress_in_experimental_diabetic_neuropathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(06)00211-6 DB - PRIME DP - Unbound Medicine ER -