Vitamin C Improves Gastroparesis in Diabetic Rats: Effects on Gastric Contractile Responses and Oxidative Stress

Dig Dis Sci. 2017 Sep;62(9):2338-2347. doi: 10.1007/s10620-017-4632-9. Epub 2017 Jun 21.

Abstract

Background: Diabetic gastroparesis is a common complication of diabetes mellitus, which mainly affects women. Previous studies have demonstrated that oxidative stress is involved in its onset and development.

Aims: This study evaluated the role of vitamin C on diabetes-associated gastric dysmotility.

Methods: Female rats with streptozotocin-induced diabetes were treated with vehicle (water, 1 mL/kg, p.o.), vitamin C (300 mg/kg/day, p.o.), or insulin (6 IU/day, s.c.). Gastric emptying, in vitro gastric contractility, and biochemistry parameters were analyzed at the end of the treatment (i.e. 8 weeks after the diabetes induction).

Results: Vitamin C reversed the delayed gastric emptying of diabetic rats to normal levels, and avoided the changes in the contractile responses to acetylcholine (0.1 nM-1 µM), but not to 5-hydroxytryptamine (0.1 nM-1 µM), in the pylorus and fundus from diabetic rats. Moreover, the contraction evoked by KCl (40 mM) in the fundus, but not in the pylorus, was intensely increased in diabetic rats treated with vitamin C. Notably, the vitamin C reestablished the reduced glutathione levels by 77% and decreased the reactive oxygen species content by 60% in the gastric tissue from diabetic rats. Despite the effects on gastric motility, vitamin C treatment did not change the fasting glycaemia or the glycated hemoglobin of diabetic rats. Unsurprisingly, insulin treatment normalized all parameters evaluated.

Conclusions: Vitamin C exhibited a remarkable beneficial effect on gastric emptying dysfunction in diabetic rats, which was mediated by attenuation of oxidative stress and maintenance of the cholinergic contractile responses in fundus and pylorus.

Keywords: Antioxidant; Ascorbic acid; Diabetes; Gastric emptying; Gastroparesis; Streptozotocin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Dose-Response Relationship, Drug
  • Female
  • Gastric Emptying / drug effects*
  • Gastric Emptying / physiology
  • Gastroparesis / drug therapy*
  • Gastroparesis / metabolism
  • Gastroparesis / physiopathology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Treatment Outcome

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Ascorbic Acid