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Published in: Journal of Diabetes & Metabolic Disorders 1/2023

13-01-2023 | Insulins | Research article

Melatonin improves liver and pancreatic tissue injuries in diabetic rats: role on antioxidant enzymes

Authors: Onur Ertik, Bertan Boran Bayrak, Goksel Sener, Refiye Yanardag

Published in: Journal of Diabetes & Metabolic Disorders | Issue 1/2023

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Abstract

Purpose

Melatonin (Mel) is an indolamine mainly synthesized by the pineal gland and many other organs. It plays an important role in scavenging free radicals and stimulating antioxidant enzymes. The goal of this study was to investigate the effect of Mel and/or insulin treatment on oxidative liver and pancreas injuries in diabetic rats.

Methods

Male Wistar albino rats were assigned into 5 groups. Group I: control animals. Group II: diabetes was induced via a single dose of STZ (60 mg/kg) administered intraperitoneally. Group III: diabetic rats treated with Mel (10 mg/kg/day). Group IV: diabetic rats given insulin (6U/kg) subcutaneously. Group V: diabetic rats that received insulin and Mel at the same dose and time. After 12 weeks of the experiment, the animals were decapitated, liver and pancreas tissues were collected.

Results

The results indicated that reduced glutathione levels in liver and pancreatic tissue decreased, while protein carbonyl, advanced oxidized protein products and lipid peroxidation levels were elevated in diabetic group. Antioxidant enzyme activities decreased in liver tissues but increased in pancreatic tissues of the diabetic group. Administration of Mel, insulin or Mel + insulin reversed these biochemical changes in the diabetic animals.

Conclusion

This work shows that in long-term oxidative stress conditions caused by STZ-induced diabetes, either Mel or Mel + insulin administration may improve the deteriorated oxidant/antioxidant system in both the liver and pancreas tissues. These results suggested that Mel alone or Mel + insulin treatments might have a significant role in protecting against liver and pancreatic damage in STZ diabetic rats via different antioxidant effects.
Literature
6.
go back to reference Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE. Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med. 1967;126:201–5.CrossRefPubMed Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE. Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med. 1967;126:201–5.CrossRefPubMed
7.
go back to reference Paskaloglu K, Sener G, Ayangolu-Dulger G. Melatonin treatment protects against diabetes-induced functional and biochemical changes in rat aorta and corpus cavernosum. Eur J Pharmacol. 2004;499:345–54.CrossRefPubMed Paskaloglu K, Sener G, Ayangolu-Dulger G. Melatonin treatment protects against diabetes-induced functional and biochemical changes in rat aorta and corpus cavernosum. Eur J Pharmacol. 2004;499:345–54.CrossRefPubMed
8.
go back to reference Beutler E. Glutathione in red cell metabolism: a manual of biochemical methods. second ed. New York: Grune & Stratton; 1975. pp. 112–4. Beutler E. Glutathione in red cell metabolism: a manual of biochemical methods. second ed. New York: Grune & Stratton; 1975. pp. 112–4.
16.
go back to reference Beutler E. Red cell metabolism. A manual of biochemical methods. Vol. 12. London: Academic Press; 1971. pp. 68–70. Beutler E. Red cell metabolism. A manual of biochemical methods. Vol. 12. London: Academic Press; 1971. pp. 68–70.
27.
go back to reference Gilani SJ, Bin-Jumah MN, Al-Abbasi FA, Nadeem MS, Afzal M, Sayyed N, Kazmi I. Fustin ameliorates hyperglycemia in streptozotocin induced type-2 diabetes via modulating glutathione/Superoxide dismutase/Catalase expressions, suppress lipid peroxidation and regulates histopathological changes. Saudi J Biol Sci. 2021;28:6963–71. https://doi.org/10.1016/j.sjbs.2021.07.070.CrossRef Gilani SJ, Bin-Jumah MN, Al-Abbasi FA, Nadeem MS, Afzal M, Sayyed N, Kazmi I. Fustin ameliorates hyperglycemia in streptozotocin induced type-2 diabetes via modulating glutathione/Superoxide dismutase/Catalase expressions, suppress lipid peroxidation and regulates histopathological changes. Saudi J Biol Sci. 2021;28:6963–71. https://​doi.​org/​10.​1016/​j.​sjbs.​2021.​07.​070.CrossRef
36.
go back to reference Kalousova M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res. 2002;51:597–604.PubMed Kalousova M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res. 2002;51:597–604.PubMed
38.
go back to reference Jakuš V, Sándorová E, Kalninová J, Krahulec B. Monitoring of glycation, oxidative stress and inflammation in relation to the occurrence of vascular complications in patients with type 2 diabetes mellitus. Physiol Res. 2014;63:297–309.CrossRefPubMed Jakuš V, Sándorová E, Kalninová J, Krahulec B. Monitoring of glycation, oxidative stress and inflammation in relation to the occurrence of vascular complications in patients with type 2 diabetes mellitus. Physiol Res. 2014;63:297–309.CrossRefPubMed
42.
go back to reference Djordjevic B, Cvetkovic T, Stoimenov TJ, Despotovic M, Zivanovic S, Basic J, Veljkovic A, Velickov A, Kocic G, Pavlovic D, Sokolovic D. Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes. Eur J Pharmacol. 2018;833:290–7. https://doi.org/10.1016/j.ejphar.2018.06.011.CrossRefPubMed Djordjevic B, Cvetkovic T, Stoimenov TJ, Despotovic M, Zivanovic S, Basic J, Veljkovic A, Velickov A, Kocic G, Pavlovic D, Sokolovic D. Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes. Eur J Pharmacol. 2018;833:290–7. https://​doi.​org/​10.​1016/​j.​ejphar.​2018.​06.​011.CrossRefPubMed
53.
go back to reference Qujeq D, Rezvani T. Catalase (antioxidant enzyme) activity in streptozotocin-induced diabetic rats. Int J Diabetes Metab. 2007;15:22–4. Qujeq D, Rezvani T. Catalase (antioxidant enzyme) activity in streptozotocin-induced diabetic rats. Int J Diabetes Metab. 2007;15:22–4.
54.
go back to reference Gonzalez A, Estaras M, Martinez-Morcillo S, Martinez R, García A, Estévez M, Santofimia-Castaño P, Tapia JA, Moreno N, Pérez-López M, Míguez MP, Blanco-Fernández G, Lopez-Guerra D, Fernandez-Bermejo M, Mateos JM, Vara D, Roncero V, Salido GM. Melatonin modulates red-ox state and decreases viability of rat pancreatic stellate cells. Sci Rep. 2020;10:6352. https://doi.org/10.1038/s41598-020-63433-6.CrossRefPubMedPubMedCentral Gonzalez A, Estaras M, Martinez-Morcillo S, Martinez R, García A, Estévez M, Santofimia-Castaño P, Tapia JA, Moreno N, Pérez-López M, Míguez MP, Blanco-Fernández G, Lopez-Guerra D, Fernandez-Bermejo M, Mateos JM, Vara D, Roncero V, Salido GM. Melatonin modulates red-ox state and decreases viability of rat pancreatic stellate cells. Sci Rep. 2020;10:6352. https://​doi.​org/​10.​1038/​s41598-020-63433-6.CrossRefPubMedPubMedCentral
55.
go back to reference Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med. 2016;95:27–42.CrossRefPubMed Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med. 2016;95:27–42.CrossRefPubMed
58.
go back to reference Sadeghabadi AZ, Abbasalipourkabir R, Mohseni R, Ziamajidi N. Investigation of oxidative stress markers and antioxidant enzymes activity in newly diagnosed type 2 diabetes patients and healthy subjects, association with IL-6 level. J Diabetes Metab Disord. 2019;18:437–43. https://doi.org/10.1007/s40200-019-00437-8.CrossRef Sadeghabadi AZ, Abbasalipourkabir R, Mohseni R, Ziamajidi N. Investigation of oxidative stress markers and antioxidant enzymes activity in newly diagnosed type 2 diabetes patients and healthy subjects, association with IL-6 level. J Diabetes Metab Disord. 2019;18:437–43. https://​doi.​org/​10.​1007/​s40200-019-00437-8.CrossRef
59.
go back to reference Verma S, Sagar N, Vats P, Shukla KN, Abbas M, Banerjee M. Antioxidant enzyme levels as markers for type 2 diabetes mellitus. Int J Bioassays. 2013;2:685–90. Verma S, Sagar N, Vats P, Shukla KN, Abbas M, Banerjee M. Antioxidant enzyme levels as markers for type 2 diabetes mellitus. Int J Bioassays. 2013;2:685–90.
Metadata
Title
Melatonin improves liver and pancreatic tissue injuries in diabetic rats: role on antioxidant enzymes
Authors
Onur Ertik
Bertan Boran Bayrak
Goksel Sener
Refiye Yanardag
Publication date
13-01-2023
Publisher
Springer International Publishing
Keywords
Insulins
Insulins
Published in
Journal of Diabetes & Metabolic Disorders / Issue 1/2023
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-022-01179-w

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