Log in

Sleeve Gastrectomy Ameliorates Diabetes-Related Spleen Damage by Improving Oxidative Stress Status in Diabetic Obese Rats

  • Original Contributions
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Purpose

Oxidative stress and inflammation are important pathogenic mediators in diabetes-related organ damage. Accumulating evidence suggests that immunodeficiency in diabetes is associated with diabetes-induced spleen damage. Sleeve gastrectomy (SG) has been proved to improve diabetes and its multiple associated complications. However, the ameliorative role of SG against spleen damage in diabetes has not been investigated.

Materials and Methods

Animal model of diabetic obese rats induced by high-fat diet (HFD) combined with streptozotocin (STZ) was treated with sham operation, caloric restriction, and SG. Metabolic parameters were measured, and the morphological and histopathological changes, status of oxidative stress, and levels of inflammatory factors were evaluated.

Results

SG reduced body weight and improved glucose tolerance and insulin sensitivity in diabetic obese rats. SG significantly reversed splenic atrophy and alleviated abnormalities of white and red pulp. Additionally, SG also reversed the increased splenocyte apoptosis (P < 0.001). Meanwhile, indicators of oxidative stress including reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and protein carbonylation were reduced, and the activity and expression of antioxidant enzymes including SOD and CAT were improved after SG. The mRNA expression of inflammatory factors in SG groups such as TNF-α (P < 0.001), IL-6 (P < 0.001), MCP-1 (P < 0.01), and ICAM-1 (P < 0.001) was also significantly reduced.

Conclusion

SG ameliorates diabetes-related splenic injury by restoring the balance between oxidative stress process and antioxidant defense systems as well as reducing inflammation in the spleen. These findings indicate that SG is an appropriate therapeutic strategy for diabetes-related spleen damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88–98.

    PubMed  Google Scholar 

  2. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014;13(6):465–76.

    CAS  PubMed  Google Scholar 

  4. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 1999;26(3–4):259–65.

    CAS  PubMed  Google Scholar 

  5. Rashid K, Chowdhury S, Ghosh S, et al. Curcumin attenuates oxidative stress induced NFκB mediated inflammation and endoplasmic reticulum dependent apoptosis of splenocytes in diabetes. Biochem Pharmacol. 2017;143:140–55.

    CAS  PubMed  Google Scholar 

  6. Critchley JA, Carey IM, Harris T, et al. Glycemic control and risk of infections among people with type 1 or type 2 diabetes in a large primary care cohort study. Diabetes Care. 2018;41(10):2127–35.

    CAS  PubMed  Google Scholar 

  7. Mahmoud MH, Badr G, Badr BM, et al. Elevated IFN-alpha/beta levels in a streptozotocin-induced type I diabetic mouse model promote oxidative stress and mediate depletion of spleen-homing CD8+ T cells by apoptosis through impaired CCL21/CCR7 axis and IL-7/CD127 signaling. Cell Signal. 2015;27(10):2110–9.

    CAS  PubMed  Google Scholar 

  8. Kowluru RA, Kowluru A, Mishra M, et al. Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Prog Retin Eye Res. 2015;48:40–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40(4):405–12.

    CAS  PubMed  Google Scholar 

  10. Sinha K, Das J, Pal PB, et al. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 2013;87(7):1157–80.

    CAS  PubMed  Google Scholar 

  11. Manna P, Ghosh J, Das J, et al. Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: protective role of arjunolic acid. Toxicol Appl Pharmacol. 2010;244(2):114–29.

    CAS  PubMed  Google Scholar 

  12. Sjöström L, Peltonen M, Jacobson P, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA. 2014;311(22):2297–304.

    PubMed  Google Scholar 

  13. Cabré N, Luciano-Mateo F, Fernández-Arroyo S, et al. Laparoscopic sleeve gastrectomy reverses non-alcoholic fatty liver disease modulating oxidative stress and inflammation. Metabolism. 2019;99:81–9.

    PubMed  Google Scholar 

  14. Bell LN, Temm CJ, Saxena R, et al. Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content. Ann Surg. 2010;251(6):1041–8.

    PubMed  PubMed Central  Google Scholar 

  15. Monzo-Beltran L, Vazquez-Tarragón A, Cerdà C, et al. One-year follow-up of clinical, metabolic and oxidative stress profile of morbid obese patients after laparoscopic sleeve gastrectomy. 8-oxo-dG as a clinical marker. Redox Biol. 2017;12:389–402.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Schmatz R, Bitencourt MR, Patias LD, et al. da CAG, Zanini D, et al. evaluation of the biochemical, inflammatory and oxidative profile of obese patients given clinical treatment and bariatric surgery. Clin Chim Acta. 2017;465:72–9.

    CAS  PubMed  Google Scholar 

  17. Ghosh S, Chowdhury S, Sarkar P, et al. Ameliorative role of ferulic acid against diabetes associated oxidative stress induced spleen damage. Food Chem Toxicol. 2018;118:272–86.

    CAS  PubMed  Google Scholar 

  18. Cheng Y, Huang X, Wu D, et al. Sleeve gastrectomy with bypass of proximal small intestine provides better diabetes control than sleeve gastrectomy alone under postoperative high-fat diet. Obes Surg. 2019;29(1):84–92.

    PubMed  Google Scholar 

  19. Bruinsma BG, Uygun K, Yarmush ML, et al. Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice. Nat Protoc. 2015;10(3):495–507.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.

    CAS  PubMed  Google Scholar 

  21. Ishida T, Iizuka M, Ou Y, et al. Juzentaihoto hot water extract alleviates muscle atrophy and improves motor function in streptozotocin-induced diabetic oxidative stress mice. J Nat Med. 2019;73(1):202–9.

    CAS  PubMed  Google Scholar 

  22. Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, et al. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018;9(2):119.

    PubMed  PubMed Central  Google Scholar 

  23. Nisoli E, Carruba MO. Nitric oxide and mitochondrial biogenesis. J Cell Sci. 2006;119(Pt 14):2855–62.

    CAS  PubMed  Google Scholar 

  24. Dean RT, Fu S, Stocker R, et al. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J. 1997;324(Pt 1):1–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? J Cell Biochem. 2017;118(11):3577–85.

    CAS  PubMed  Google Scholar 

  26. Newsholme P, Cruzat VF, Keane KN, et al. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J. 2016;473(24):4527–50.

    CAS  PubMed  Google Scholar 

  27. O'Brien R, Johnson E, Haneuse S, et al. Microvascular outcomes in patients with diabetes after bariatric surgery versus usual care: a matched cohort study. Ann Intern Med. 2018;169(5):300–10.

    PubMed  PubMed Central  Google Scholar 

  28. Fisher DP, Johnson E, Haneuse S, et al. Association between bariatric surgery and macrovascular disease outcomes in patients with type 2 diabetes and severe obesity. JAMA. 2018;320(15):1570–82.

    PubMed  PubMed Central  Google Scholar 

  29. Hao J, Shen W, Tian C, et al. Mitochondrial nutrients improve immune dysfunction in the type 2 diabetic Goto-Kakizaki rats. J Cell Mol Med. 2009;13(4):701–11.

    CAS  PubMed  Google Scholar 

  30. Altunkaynak BZ, Ozbek E, Altunkaynak ME. A stereological and histological analysis of spleen on obese female rats, fed with high fat diet. Saudi Med J. 2007;28(3):353–7.

    PubMed  Google Scholar 

  31. Gao S, Wang Z, Zhang C, et al. Oral exposure to atrazine induces oxidative stress and calcium homeostasis disruption in spleen of mice. Oxidative Med Cell Longev. 2016;2016:7978219.

    Google Scholar 

  32. Ighodaro OM. Molecular pathways associated with oxidative stress in diabetes mellitus. Biomed Pharmacother. 2018;108:656–62.

    CAS  PubMed  Google Scholar 

  33. Sayed LH, Badr G, Omar HM, et al. Camel whey protein improves oxidative stress and histopathological alterations in lymphoid organs through Bcl-XL/Bax expression in a streptozotocin-induced type 1 diabetic mouse model. Biomed Pharmacother. 2017;88:542–52.

    CAS  PubMed  Google Scholar 

  34. Rashid K, Bhattacharya S, Sil PC. Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway. Free Radic Res. 2012;46(3):240–52.

    CAS  PubMed  Google Scholar 

  35. Rochette L, Zeller M, Cottin Y, et al. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta. 2014;1840(9):2709–29.

    CAS  PubMed  Google Scholar 

  36. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem. 2015;97:55–74.

    CAS  Google Scholar 

  37. Teng X, Zhang W, Song Y, et al. Protective effects of Ganoderma lucidum triterpenoids on oxidative stress and apoptosis in the spleen of chickens induced by cadmium. Environ Sci Pollut Res Int. 2019;26(23):23967–80.

    CAS  PubMed  Google Scholar 

  38. Naik E, Dixit VM. Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J Exp Med. 2011;208(3):417–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Mandrup-Poulsen T, Pickersgill L, Donath MY. Blockade of interleukin 1 in type 1 diabetes mellitus. Nat Rev Endocrinol. 2010;6(3):158–66.

    CAS  PubMed  Google Scholar 

  40. van Den Engel NK, Heidenthal E, Vinke A, et al. Circulating forms of intercellular adhesion molecule (ICAM)-1 in mice lacking membranous ICAM-1. Blood. 2000;95(4):1350–5.

    Google Scholar 

  41. Min T, Prior SL, Dunseath G, et al. Temporal effects of bariatric surgery on adipokines, inflammation and oxidative stress in subjects with impaired glucose homeostasis at 4 years of follow-up. Obes Surg. 2020;30(5):1712–8.

    PubMed  PubMed Central  Google Scholar 

  42. Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care. 2003;26(5):1589–96.

    CAS  PubMed  Google Scholar 

  43. Hajiluian G, Abbasalizad Farhangi M, Nameni G, et al. Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats. Nutr Neurosci. 2018;21(10):744–52.

    CAS  PubMed  Google Scholar 

  44. Sjostrom L, Peltonen M, Jacobson P, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA. 2014;311(22):2297–304.

    PubMed  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (NSFC, Grant No.81370496 and 81873647) and the Youth Program of National Natural Science Foundation of China (Grant No.81600059).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guangyong Zhang.

Ethics declarations

Conflict of Interest

All authors declare that they have no conflict of interest.

Ethical Approval

All applicable institutional and/or national guidelines for the care and use of animals were followed.

Informed Consent Statement

Informed Consent does not apply.

Dataset

Research data of the current study is available at **ong, Yacheng (2020), “Sleeve Gastrectomy Ameliorates Diabetes-related Spleen Damage by Improving Oxidative Stress Status in Diabetic Obese Rats”, Mendeley Data, v3. https://doi.org/10.17632/c8c52sxh8h.3

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, M., **ong, Y., Zhu, W. et al. Sleeve Gastrectomy Ameliorates Diabetes-Related Spleen Damage by Improving Oxidative Stress Status in Diabetic Obese Rats. OBES SURG 31, 1183–1195 (2021). https://doi.org/10.1007/s11695-020-05073-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-020-05073-3

Keywords

Navigation