Luisa Mota Da Silva1,2, Rita de Cássia Melo Vilhena de Andrade Fonseca da Silva3, Daniele Maria-Ferreira3, Olair Carlos Beltrame4, José Eduardo da Silva-Santos5, Maria Fernanda de Paula Werner3. 1. Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brazil. lu.isamota@hotmail.com. 2. Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade do Vale do Itajaí, Itajaí, SC, Brazil. lu.isamota@hotmail.com. 3. Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brazil. 4. Departamento de Medicina Veterinária, Hospital Veterinário, Universidade Federal do Paraná, Curitiba, PR, Brazil. 5. Laboratory of Cardiovascular Biology, Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
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.
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 diabeticrats 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 diabeticrats. Moreover, the contraction evoked by KCl (40 mM) in the fundus, but not in the pylorus, was intensely increased in diabeticrats 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 diabeticrats. Despite the effects on gastric motility, vitamin C treatment did not change the fasting glycaemia or the glycated hemoglobin of diabeticrats. Unsurprisingly, insulin treatment normalized all parameters evaluated. CONCLUSIONS:Vitamin C exhibited a remarkable beneficial effect on gastric emptying dysfunction in diabeticrats, which was mediated by attenuation of oxidative stress and maintenance of the cholinergic contractile responses in fundus and pylorus.
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