Obesity during pregnancy and lactation increases the inflammatory response and reduces the efficacy of nimesulide in the offspring of wistar rats

Authors

DOI:

https://doi.org/10.21527/2176-7114.2025.50.14910

Keywords:

Western Diet, Acute inflammation, Nimesulide

Abstract

The type of diet consumed during pregnancy and early life increases the possibility of developing metabolic syndrome, which can result in altered efficacy of some drugs. The aim of this study was to evaluate the inflammatory response in the offspring of Wistar rats fed a Western diet (WFD) and the anti-inflammatory effect of nimesulide. Twenty Wistar rats and their male offspring were used. The dams were divided on the 1st day of gestation into two groups: 1) DPgl: received standard diet (SD) and 2) DOgl: received DO, both from gestation to the end of lactation. On the 21st day of lactation, the male offspring were divided into six groups (n=5 animals/group) and assigned to different experimental protocols, in order to assess on the 60th day of life the influence of the type of diet on the inflammatory response (through carrageenan-induced paw oedema) and the anti-inflammatory action of nimesulide (5 mg/kg, i.p), by quantifying the levels of IL-6, TNF-α and myeloperoxidase (MPO) in the plantar tissue of the rats. The volume of edema was greater in the offspring of DOgl dams, regardless of whether they received PD or DO post-weaning; in those that received DO, the activity of nimesulide was reduced and the levels of IL-6, TNF-α and MPO were elevated. In the offspring of DPgl dams, which received PD post-weaning, the anti-inflammatory activity of nimesulide, verified in the paw volume, was maintained at all three evaluation times. Thus, the inflammatory response was more significant in the DOgl offspring that received DO, and these animals showed a reduction in the anti-inflammatory effect of nimesulide.

References

1Ward Z.J., et al. Projected US state-level prevalence of adult obesity and severe obesity. New England Journal of Medicine, 2019, v. 381, n. 25, p. 2440-2450, doi: 10.1056/NEJMsa1909301.

2 Malindisa E.K., et al. The magnitude of type 2 diabetes mellitus and cardiovascular disease risk factors among young adults in urban settings: a cross-sectional survey in Mwanza, Tanzania. The Pan African Medical Journal, 2022, v. 42, doi: 10.11604/pamj.2022.42.19.22184.

3 Organização Mundial da Saúde (OMS). Doenças não comunicáveis. 2021. Disponível online: https://www.who.int/news-room/fact-sheets/detail/noncommunicable diseases (acessado em 12 de julho de 2023).

4WHO (World Health Organization). Obesidad y sobrepeso https://www.who.int/health-topics/obesity#tab=tab_1 (Acesso em 20.06.2024). 2024

5Pan F, et al. Association between Ultra-Processed Food Consumption and Metabolic Syndrome among Adults in China—Results from the China Health and Nutrition Survey. Nutrients, 2023, v. 15, n. 3, p. 752, doi: 10.3390/nu15030752.

6Speelman, Tammy et al. The association of acute phase proteins in stress and inflammation-induced T2D. Cells, 2022, v. 11, n. 14, p. 2163, doi: 10.3390/cells11142163.

7Mantovani, Alberto; Garlanda, Cecilia. Humoral innate immunity and acute-phase proteins. New England Journal of Medicine, 2023, v. 388, n. 5, p. 439-452, doi: 10.1056/NEJMra2206346.

8Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022 Sep;19(9):593-606. doi: 10.1038/s41569-022-00679-9.

9Pagano, Cristina et al. Advances in “adiponcosis”: Insights in the inner mechanisms at the base of adipose and tumour tissues interplay. International Journal of Cancer, 2023 Jun 15;152(12):2464-2473, https://doi.org/10.1002/ijc.34355.

10Lessa, Paulo Mageste et al. Major evidence of nutrological regulation in obese patients with meta-inflammation: a systematic review. International Journal of Nutrology, 2022. International Journal of Nutrology 15(3), DOI: 10.54448/IJN22307.

11Tsujimoto, S. et al. Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ. Int J Mol Med. 2016, 38(3):721-8, doi: 10.3892/ijmm.2016.2674.

12Nowak, Paulina; BIL-LULA, Iwona; Śliwińska-Mossoń, Mariola. A Cross-Talk about Radioresistance in Lung Cancer—How to Improve Radiosensitivity According to Chinese Medicine and Medicaments That Commonly Occur in Pharmacies. International Journal of Molecular Sciences, 2023, v. 24, n. 13, p. 11206, doi: 10.3390/ijms241311206.

13LI, Z.-M. Role of antioxidants in preventing testicular ischemia reperfusion injury: a narrative review. European Review for Medical & Pharmacological Sciences, 2022, v. 26, n. 24, doi: 10.26355/eurrev_202212_30663.

14Ozleyen, Adem et al. Looking at NSAIDs from a historical perspective and their current status in drug repurposing for cancer treatment and prevention. Journal of Cancer Research and Clinical Oncology, 2023, v. 149, n. 5, p. 2095-2113, doi: 10.1007/s00432-022-04187-8.

15Ferro-Cavalcante, T.C. et al. Effects of a westernized diet on the reflexes and physical maturation of male rat offspring during the perinatal period. Lipids, 2013, 48, 1157-1168, doi: 10.1007/s11745-013-3833-z.

16Ferro-Cavalcante, T.C. et al. Early exposure of dams to a westernized diet has long-term consequences on food intake and physiometabolic homeostasis of the rat offspring. Int J Food Sci Nutr. 2014, 65, 989-993, doi: 10.3109/09637486.2014.950208.

17Winter, C.A. et al. Carrageenan-induced edema in hind paw of the rats as an assay for anti-inflammatory drugs. Proceedings of the Society for Experimental Biology and Medicine, 1962,111, 544-547, doi: 10.3181/00379727-111-27849.

18Bradley PP, Christensen RD, Rothstein G (1982) Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood 60: 618–622, doi.org/10.1182/blood.V60.3.618.618.

19Chakaroun, Rima Mohsen; Olsson, Lisa M.; Bäckhed, Fredrik. The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease. Nature Reviews Cardiology. 2023, v. 20, n. 4, p. 217-235, doi: 10.1038/s41569-022-00771-0.

20Turchi, R., Tortolici, F., Guidobaldi, G. et al. Frataxin deficiency induces lipid accumulation and affects thermogenesis in brown adipose tissue. Cell Death Dis 11, 51 (2020). https://doi.org/10.1038/s41419-020-2253-2

21Garcia BM, et al., Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis. Molecular Human Reproduction, Volume 26, Issue 12, December 2020, Pages 938–952, https://doi.org/10.1093/molehr/gaaa071.

22Drozdz, Dorota et al. Obesity and cardiometabolic risk factors: from childhood to adulthood. Nutrients. 2021, v. 13, n. 11, p. 4176, doi: 10.3390/nu13114176.

23Faienza, Maria Felicia et al. Childhood obesity, cardiovascular and liver health: a growing epidemic with age. World Journal of Pediatrics, 2020, v. 16, p. 438-445, doi: 10.1007/s12519-020-00341-9.

24Desai, M. et al. Maternal obesity and high-fat diet program offspring metabolic syndrome. Am J Obstet Gynecol. 2014. Sep;211, Sep;211(3):237.e1-237.e13., doi: 10.1016/j.ajog.2014.03.025.

25Buzinaro, E.F.; Berchieri, C.B.; Haddad, A.L.M.; Padovani, C.R.; Pimenta, W.P. Sobrepeso na Adolescência de Filhos de Mães que Tiveram Distúrbios Glicêmicos na Gestação. Arq Bras Endrocrinol Metab. v.52, n.1, p.85-92, 2008

26Glastras, S.J.; Chen, H.; Tsang, M.; Teh, R.; McGrath, R.T.; Zaky, A.; Chen, J.; Wong, M.G.; Pollock, C.A.; Saad, S. The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet. PloS One, 2017, Feb 22; 12(2):e0172644, https://doi.org/10.1371/journal.pone.0172644.

27Azab AN, Kaplanski J. A reduction of tumor necrosis factor-alpha in paw exudate of lipopolysaccharide treated rats by nimesulide. Life Sci. 2001 Feb 23;68(14):1667-75. doi: 10.1016/s0024-3205(01)00960-2. PMID: 11263679.

28Liang Y, Huang B, Song E, Bai B, Wang Y. Constitutive activation of AMPK α1 in vascular endothelium promotes high-fat diet-induced fatty liver injury: role of COX-2 induction. Br J Pharmacol. 2014 Jan;171(2):498-508. doi: 10.1111/bph.12482. PMID: 24372551; PMCID: PMC3904267.

29Iannitti T, Graham A, Dolan S. Increased central and peripheral inflammation and inflammatory hyperalgesia in Zucker rat model of leptin receptor deficiency and genetic obesity. Exp Physiol. 2012 Nov;97(11):1236-45. doi: 10.1113/expphysiol.2011.064220. Epub 2012 Apr 20. PMID: 22523380.

30Ngcobo SR, Nkambule BB, Nyambuya TM, Mokgalaboni K, Ntsethe A, Mxinwa V, Ziqubu K, Ntamo Y, Nyawo TA, Dludla PV. Activated monocytes as a therapeutic target to attenuate vascular inflammation and lower cardiovascular disease-risk in patients with type 2 diabetes: A systematic review of preclinical and clinical studies. Biomed Pharmacother. 2022 Feb;146:112579. doi: 10.1016/j.biopha.2021.112579. Epub 2021 Dec 30. PMID: 35062054.

31Hosogai, N. et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes, 2007, 56: 901–11, doi: 10.2337/db06-0911.

32Warbrick I, Rabkin SW. Hypoxia-inducible factor 1-alpha (HIF-1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction. Obes Rev. 2019 May;20(5):701-712. doi: 10.1111/obr.12828. Epub 2019 Mar 3. PMID: 30828970.

33Sun, K. et al. Adipose tissue remodeling and obesity. J Clin Invest 2011 Jun;121(6):2094-101. doi: 10.1172/JCI45887.

34Fantuzzi, G., 2005. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol.115, 911-9, doi: 10.1016/j.jaci.2005.02.023.

35White PA, Cercato LM, Araújo JM, Souza LA, Soares AF, Barbosa AP, Neto JM, Marçal AC, Machado UF, Camargo EA, Santos MR, Brito LC. Model of high-fat diet-induced obesity associated to insulin resistance and glucose intolerance. Arq Bras Endocrinol Metabol. 2013 Jul;57(5):339-45. Portuguese. doi: 10.1590/s0004-27302013000500002. PMID: 23896799.

36 Lacerda DR, Nunes-Silva A, Silveira ALM, Costa KA, Rodrigues DF, Moraes MM, Pinho V, Menezes GB, Teixeira MM, Wanner SP, Soares DD, Ferreira AVM. Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice. Nutrition. 2023 Nov; 115:112092. doi: 10.1016/j.nut.2023.112092. Epub 2023 May 30. PMID: 37549454.

37 Catarro M, Serrano JL, Ramos SS, Silvestre S, Almeida P. Nimesulide analogues: From anti-inflammatory to antitumor agents. Bioorg Chem. 2019 Jul;88:102966. doi: 10.1016/j.bioorg.2019.102966. Epub 2019 Apr 30. PMID: 31075744.

38 Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71-87. doi: 10.2165/11318100-000000000-00000. PMID: 20067334.

39Morrish, G.A.; Pai, M.P.; Green, B. The effects of obesity on drug pharmacokinetics in humans. Expert opinion on drug metabolism & toxicology. 2011; p.697-706, Doi. 10.1517/17425255.2011.570331

Published

2025-03-24

How to Cite

Franco, E. de S., Menezes, T. M., Lima, L. C. de A. S., Bacelar, V. K. S. S., Nascimento, E. do, & Maia, M. B. de S. (2025). Obesity during pregnancy and lactation increases the inflammatory response and reduces the efficacy of nimesulide in the offspring of wistar rats. Revista Contexto & Saúde, 25(50), e14910. https://doi.org/10.21527/2176-7114.2025.50.14910

Issue

Section

ORIGINAL ARTICLE