Effect of acetyl-L-carnitine on Vip-ergic neurons in jejunum submucous plexus of diabetic rats

Abstract

-The effect of the treatment with acetyl-L-carnitine (ALC) on neurons releasing the vasoactive intestinal polypeptide (VIP) of the submucous plexus in the jejunum of diabetic rats was the purpose of our investigation. Diabetes (DM) was induced by injecting streptozotocin endovenously (35mg/kg). After sacrificing the animals, the jejunum was collected and processed for VIP detection. Four groups were used: C (nondiabetic), CC (non-diabetic treated with ALC), D (diabetic), DC (diabetes treated with ALC). We analyzed the immunoreactivity and the cellular profile of 126 cell bodies. The treatment with ALC improved some aspects of DM. However, it promoted a small increase in the area of neurons from group CC, suggesting a possible neurotrophic effect. Neurons from groups D and DC showed a large increase in their cellular profile and immunoreactivity when compared to C and CC, suggesting a larger concentration of this neurotransmitter within the neurons that produce it. This observation constitutes a recurrent finding in diabetic animals, suggesting that ALC doesnot interfere in the pathophysiological mechanisms that unchain a higher production and/or neurotransmitter accumulation and increase the profile of the VIP-ergic neurons.KEY WORDS: acetyl-L-carnitine, submucous plexus, VIP, diabetes, jejunum, rat. Efeito da acetil-L-carnitina sobre neurônios Vip-érgicos do plexo submucoso do jejuno de ratos diabéticosRESUMO -Investigamos o efeito da acetil-L-carnitina (ALC) sobre os neurônios que expressam o peptídeo intestinal vasoativo (VIP) do plexo submucoso no jejuno de ratos diabéticos. O diabetes (DM) foi induzido pela administração endovenosa de estreptozootocina (35mg/kg). Após o sacrifício dos animais, o jejuno foi coletado e processado para a detecção de VIP. Utilizou-se quatro grupos: C (não diabéticos), CC (não diabéticos suplementados com ALC), D (diabéticos) e DC (diabéticos suplementados com ALC). Analisou-se a imunoreatividade e o perfil celular de 126 corpos celulares. O tratamento com ALC melhorou alguns aspectos do DM. Porém, promoveu pequeno aumento na área dos neurônios do grupo CC, indicando possível efeito neurotrófico. Neurônios dos grupos D e DC apresentaram grande aumento do perfil celular e na imunoreatividade em relação a C e CC, sugerindo maior concentração deste neurotransmissor nestes neurônios. Esta observação é constante em animais diabéticos, sugerindo que a ALC não interfere nos mecanismos fisiopatológicos que desencadeiam a maior produção e/ou acúmulo de neurotransmissor e aumento do perfil dos neurônios VIP-érgicos. PALAVRAS-CHAVE: acetil-L-carnitina, plexo submucoso, VIP, diabetes, jejuno, rato. Diabetes mellitus (DM) main chronic complications are, among others, vascular changes and peripheral neuropathies, which lead to gastrointestinal dysfunctions. Several hypotheses have been reported concerning the main causes for the origin of the diabetic neuropathy. Recent reports have described that the carnitine abnormal metabolism may be one of the reasons that triggers neural damage...

Combination vitamin C and vitamin E prevents enteric diabetic neuropathy in the small intestine in rats

“…Thus, we can infer that diabetes promoted a reduction of neuron metabolism, leading to the death of a portion of its neuronal population. We observed a reduction of more than half of these neurons, and diabetic neuropathy was observed, similar to studies that used other experimental models of diabetes and evaluated different regions of the gastrointestinal tract, including the stomach (Takahashi et al 1997;Fregonesi et al 2001), duodenum (Pereira et al 2006;Zanoni et al 2011;Lopes et al 2012), jejunum (Defani et al 2003;De Freitas et al 2008;Alves et al 2010;HermesUliana et al 2014), ileum Shotton and Lincoln 2006;Pereira et al 2011), cecum (Zanoni et al 1997;Zanoni et al 2011), and proximal colon (Tashima et al 2007;Roldi et al 2009). The development of neuropathy affects different types of enteric neurons, which are responsible for the control of important functions, such as motility, secretion, blood flow, and growth aspects of the local mucosal immune system (Furness 2012).…”

“…Among the chronic complications caused by diabetes, neurological manifestations are the most common, affecting both the autonomic and peripheral nervous systems and impairing the quality of life of patients (Chandrasekharan et al 2011). Our research group found that diabetes mellitus reduced the density of myenteric neurons and enteric neural plasticity in various segments of the digestive system (Takahashi et al 1997;Zanoni et al 1997;Fregonesi et al 2001;Defani et al 2003;Zanoni et al 2003;Pereira et al 2006;Tashima et al 2007;Zanoni et al 2007;De Freitas et al 2008;Roldi et al 2009;Alves et al 2010;Pereira et al 2011;Zanoni et al 2011;Lopes et al 2012;Hermes-Uliana et al 2014). These changes in enteric innervation that arise from diabetes are attributable to persistent hyperglycemia that produces numerous metabolic changes.…”

Immunohistochemical study of vasoactive intestinal peptide (VIP) enteric neurons in diabetic rats supplemented with L-glutamine

“…51 Particularly in VIP-IR neurons of the submucosal plexus of chronically diabetic animals, such alterations are represented by the increased fluorescence and cell body area. 10,31,38 From our observations and the literature data, several hypotheses have been put forward in an attempt to clarify the possible causes contributing to the increase in the cell body area, such as:…”

“…[3][4][5] The myenteric neurons of rats, soon after the induction of diabetes, show reduced neuronal activity, chromatolysis and degenerative alterations. 6 In chronic diabetes mellitus, alterations are seen in neuronal density and cell body area in several segments, such as the stomach, 7,8 duodenum, 9 jejunum, 10 ileum, [11][12][13] cecum 14 and colon. [15][16][17] Enteric neuronal subpopulations such as those expressing noradrenaline, acetylcholine, serotonine, 18 nitric oxide, 19 and vasoactive intestinal peptide (VIP), 20 respond differently to diabetes mellitus.…”

Repercussões morfológicas da lesão térmica corporal nos componentes do plexo mioentérico do jejuno de ratos adultos.

“…Por outro lado, Defani et al (2003), Fregonesi et al (2005) e Soares et al (2006) descreveram a diminuição da massa corporal em animais diabéticos tratados com glutamato monosódico, e Hernandes et al (2000) observaram diminuição significante do peso corpóreo dos animais tratados com cloreto de benzalcônio.…”