Evaluation of positive NADPH-diaphorase myenteric neurons in diabetic rats supplemented with Acetyl-L-Carnitine

Keywords: Gastrointestinal tract, Myenteric plexus, Nitric oxide

Abstract

The objective was to evaluate supplementation with acetyl-L-carnitine (ALC) on myenteric neurons of the ileum of rats after induction of diabetes. Diabetic animals supplemented with ALC (DC), diabetic (D), normoglycemic animals supplemented with ALC (CC) and normoglycemic (C) were used. NADPH-d neurons were quantified and measured. There was a reduction in blood glucose and water intake in the DC group. The neuronal density in 12.72mm² of ileum was similar in the four groups (p>0.05): DC (558.8 ± 220.2), D (513.4 ± 72.01), CC (645.2 ± 144.9) and C (934 ± 248.5). The mean cell body area of neurons (μm²) in diabetic animals, DC (303.9 ± 114.2) and D (285.4 ± 111.8), were greater than in the normoglycemic groups, CC (173.6 ± 53.78) and C (158.4 ± 53.73). The ileum area (mm²) was larger in animals of the diabetic groups, CD (190.96) and D (171.62) compared to the normoglycemic groups: CC (138.04) and C (130.04). However, in the DC group, both areas were larger than in D (p<0.05). Thus, a slight increase in neuronal population can be inferred. The data indicated that ALC did not interfere with mechanisms that promote an increase in the production of nitric oxide (NO) by myenteric neurons of the ileum and that the greater dilation of the ileum in the DC group could be the result of a side effect of the dose of carnitine used.

Author Biographies

Angela Maria Pereira Alves, Universidade Estadual de Maringá - UEM
Doctor´s degree in Biological Sciences (Cell Biology) of the Universidade Estadual de Maringá (UEM). Adjunct professor at the Universidade Estadual de Maringá, Maringá PR Brazil.
Marli Aparecida Defani, Universidade Estadual de Maringá - UEM
Doctor´s degree in Biological Sciences (Cell Biology) of the Universidade Estadual de Maringá (UEM). Adjunct professor at the Universidade Estadual de Maringá, Maringá PR Brazil.
Éder Paulo Belato Alves, Universidade Estadual de Maringá - UEM
Doctor´s degree in Biological Sciences (Cell Biology) of the Universidade Estadual de Maringá (UEM). Adjunct professor at the Universidade Estadual de Maringá, Maringá PR Brazil.
Stephanie Carvalho Borges, Universidade Estadual de Maringá - UEM
Doctor´s degree in Biological Sciences (Cell and Molecular Biology) at the Universidade Estadual de Maringá (UEM), Maringá PR Brazil.
Cristina Elena Prado Teles Fregonesi, Universidade Estadual Paulista Júlio de Mesquita Filho - UNESP
Doctor´s degree in Biological Sciences (Cell Biology) at the Universidade Estadual de Maringá (UEM). Assistant Professor of the Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Presidente Prudente SP Brazil.
Sandra Regina Stabille, Universidade Estadual de Maringá - UEM
Doctor´s degree in Morphofunctional Studies at the Universidade de São Paulo (USP/SP). Emeritus professor at the Universidade Estadual de Maringá, Maringá PR Brazil.
Marcilio Hubner de Miranda Neto, Universidade Estadual de Maringá - UEM
Doctor´s degree in Sciences at the Universidade de São Paulo (USP/SP). Full professor at the Universidade Estadual de Maringá, Maringá PR Brazil.

References

1. Naruse K. Schwann Cells as Crucial Players in Diabetic Neuropathy. In: Myelin. Springer; 2019. p. 345–56.

2. Wołoszyn-Durkiewicz A, Myśliwiec M. The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes. Pediatr Endocrinol Diabetes Metab. 2019;25(1).

3. Fang F, Wang J, Wang YF, Peng YD. Microangiopathy in diabetic polyneuropathy revisited. Eur Rev Med Pharmacol Sci. 2018;22(19):6456–62.

4. Kuhn C, Besancon A, Lemoine S, You S, Marquet C, Candon S, et al. Regulatory mechanisms of immune tolerance in type 1 diabetes and their failures. J Autoimmun. 2016;71:69–77.

5. Malik A, Morya RK, Bhadada SK, Rana S. Type 1 diabetes mellitus: Complex interplay of oxidative stress, cytokines, gastrointestinal motility and small intestinal bacterial overgrowth. Eur J Clin Invest. 2018;48(11):e13021.

6. Ramazani M, Qujeq D, Moazezi Z. Assessing the levels of L-carnitine and total antioxidant capacity in adults with newly diagnosed and long-standing type 2 diabetes. Can J diabetes. 2019;43(1):46–50.

7. Archvadze A, Kistauri A, Gongadze N, Makharadze T, Chirakadze K. MEDICAL BASIS OF DIABETIC NEUROPATHY FORMATION. Georgian Med News. 2018;(283):154–62.

8. Bene J, Hadzsiev K, Melegh B. Role of carnitine and its derivatives in the development and management of type 2 diabetes. Nutr Diabetes. 2018;8(1):1–10.

9. Tomassoni D, Mannelli LDC, Bramanti V, Ghelardini C, Amenta F, Pacini A. Treatment with acetyl-L-carnitine exerts a neuroprotective effect in the sciatic nerve following loose ligation: a functional and microanatomical study. Neural Regen Res. 2018;13(4):692.

10. Ferreira GC, McKenna MC. L-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain. Neurochem Res. 2017;42(6):1661–75.

11. Sergi G, Pizzato S, Piovesan F, Trevisan C, Veronese N, Manzato E. Effects of acetyl-L-carnitine in diabetic neuropathy and other geriatric disorders. Aging Clin Exp Res. 2018;30(2):133–8.

12. Kurniawan AH, Suwandi BH, Kholili U. Diabetic Gastroenteropathy: A Complication of Diabetes Mellitus. Acta Med Indones. 2019;51(3):263–71.

13. Pereira RVF, Linden DR, Miranda-Neto MH, Zanoni JN. Differential effects in CGRPergic, nitrergic, and VIPergic myenteric innervation in diabetic rats supplemented with 2% L-glutamine. An Acad Bras Cienc. 2016;88:609–22.

14. Hermes-Uliana C, Panizzon CP do NB, Trevizan AR, Sehaber CC, Ramalho FV, Martins HA, et al. Is L-glutathione more effective than L-glutamine in preventing enteric diabetic neuropathy? Dig Dis Sci. 2014;59(5):937–48.

15. Belai A, Lincoln J, Milner P, Burnstock G. Differential effect of streptozotocin-induced diabetes on the innervation of the ileum and distal colon. Gastroenterology. 1991;100(4):1024–32.

16. Ferreira PEB, Lopes CRP, Alves AMP, Alves ÉPB, Linden DR, Zanoni JN, et al. Diabetic neuropathy: an evaluation of the use of quercetin in the cecum of rats. World J Gastroenterol WJG. 2013;19(38):6416.

17. Stevens MJ. Nitric oxide as a potential bridge between the metabolic and vascular hypotheses of diabetic neuropathy. Diabet Med. 1995;12(4):292–5.

18. Scherer-Singler U, Vincent SR, Kimura H, McGeer EG. Demonstration of a unique population of neurons with NADPH-diaphorase histochemistry. J Neurosci Methods. 1983;9(3):229–34.

19. Miranda-Neto MH, Molinari SL, Natali MRM, Sant’Ana D de MG. Regional differences in the number and type of myenteric neurons of the ileum of rats: a comparison of techniques of the neuronal evidentiation. Arq Neuropsiquiatr. 2001;59(1):54–9.

20. Parvanova A, Trillini M, Podestà MA, Iliev IP, Aparicio C, Perna A, et al. Blood pressure and metabolic effects of acetyl-L-carnitine in type 2 diabetes: DIABASI randomized controlled trial. J Endocr Soc. 2018;2(5):420–36.

21. Muoio DM, Noland RC, Kovalik J-P, Seiler SE, Davies MN, DeBalsi KL, et al. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. Cell Metab. 2012;15(5):764–77.

22. Giancaterini A, De Gaetano A, Mingrone G, Gniuli D, Liverani E, Capristo E, et al. Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients. Metab Exp. 2000;49(6):704–8.

23. Eyth E, Naik R. Hemoglobin A1C. In: StatPearls [Internet]. StatPearls Publishing; 2019.

24. De Miranda Neto MH, Defani MA, Fregonesi C, Natali MRM, Pereira A. Morphometric and quantitative evaluation of the NADH‐diaphorase positive myenteric neurons of the jejunum of streptozotocin‐diabetic rats supplemented with acetyl‐L‐carnitine. Anat Histol Embryol. 2005;34(3):154–8.

25. Panizzona CP do NB, de Miranda Netoa MH, Ramalhoa FV, Longhinib R, de Mellob JCP, Zanonia JN. Ethyl Acetate Fraction from Trichilia catigua Confers Partial Neuroprotection in Components of the Enteric Innervation of the Jejunum in Diabetic Rats. Cell Physiol Biochem. 2019;53:76–86.

26. Pereira Alves AM, de Paula AL, Moreira CR, Ferrari F, Coelho Leal JP, Hatoum US, et al. Effects of Quercetin-Supplementation in NADH-Diaphorase Positive Neurons Subpopulations in the Ileum of Rats with Experimental Diabetes Mellitus. Int J Morphol. 2017;35(1):236–41.

27. Santer RM. Survival of the population of NADPH-diaphorase stained myenteric neurons in the small intestine of aged rats. J Auton Nerv Syst. 1994;49(2):115–21.

28. Ferreira PEB, Beraldi EJ, Borges SC, Natali MRM, Buttow NC. Resveratrol promotes neuroprotection and attenuates oxidative and nitrosative stress in the small intestine in diabetic rats. Biomed Pharmacother. 2018;105:724–33.

29. Defani MA, Zanoni JN, Natali MRM, Bazotte RB, Miranda-Neto MH de. Effect of acetyl-L-carnitine on Vip-ergic neurons in jejunum submucous plexus of diabetic rats. Arq Neuropsiquiatr. 2003;61(4):962–7.

30. Tomlinson KC. Functional consequences of streptozotocin-induced diabetes mellitus, with particular reference to the cardiovascular system. Pharmacol Rev. 1992;44:103–50.

Published
2021-12-20
Section
Artigos Originais