Effects of a-lipoic acid on impaired gastric fundus innervation in diabetic rats

Thomas Michael Gibson, Mary Anne Cotter, Norman E Cameron

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Diabetes mellitus is a major cause of neuropathy, leading to adverse effects including autonomic gastrointestinal dysfunction. Oxidative stress contributes to the etiology of diabetic neuropathy. The aim was to examine whether treatment with the antioxidant, a-lipoic acid (LA), could prevent or correct diabetic functional defects in the gastric fundus non-adrenergic, non-cholinergic (NANC) nerves, which use nitric oxide as their major neurotransmitter. LA (100 mg/kg/d) was given in a prevention study for 8 weeks following streptozotocin-diabetes induction, and in an intervention study for 4 weeks after 4 weeks of untreated diabetes. Fundus strips were studied in vitro after precontraction with 5-hydroxytryptamine in the presence of guanethidine and atropine to isolate NANC relaxation to electrical field stimulation. After 4 and 8 weeks of diabetes, there were 26% and 48% deficits in maximum relaxation, respectively. Prevention LA treatment gave 83% protection; intervention LA prevented the deterioration between 4 and 8 weeks of diabetes and corrected the initial 4 week deficit by 56%. Diabetes also resulted in a failure to maintain relaxation for prolonged stimulation, which was prevented by LA. Thus, LA prevented and reversed the development of impaired gastric fundus NANC responses in diabetic rats, which has potential therapeutic implications for gastrointestinal autonomic neuropathy. (C) 2003 Elsevier Inc.

Original languageEnglish
Pages (from-to)160-168
Number of pages8
JournalFree Radical Biology and Medicine
Volume35
Issue number2
DOIs
Publication statusPublished - Jul 2003

Keywords

  • diabetes mellitus
  • gastric fundus
  • autonomic neuropathy
  • oxidative stress
  • NANC
  • nitric oxide
  • free radicals
  • NITRIC-OXIDE SYNTHASE
  • VASOACTIVE INTESTINAL POLYPEPTIDE
  • NERVE-CONDUCTION-VELOCITY
  • ENDONEURIAL BLOOD-FLOW
  • CORPUS CAVERNOSUM
  • OXIDATIVE STRESS
  • NEUROVASCULAR DYSFUNCTION
  • ANTIOXIDANT
  • RELAXATION
  • NEUROPATHY

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