Influence of organism stimulation with bacterial lipopolysaccharide on nitric oxide production and metabolism in rat heart on the background of metabolic syndrome
DOI:
https://doi.org/10.34287/MMT.4(59).2023.6Abstract
Aim. The aim of the study was to establish the changes in nitric oxide production and metabolism in rat heart during combined influence of organism stimulation with bacterial lipopolysaccharide (LPS) and modeling of metabolic syndrome (MetS).
Materials and methods. The study was conducted on 24 mature male Wistar rats weighing 200–260 g. Experiment lasted 60 days. The animals were divided into 4 groups of 6 animals each: control group, MetS group, LPS stimulation group, LPS + MetS group. MetS was reproduced by using a 20 % fructose solution as the only source of drinking water. LPS of Salmonella typhi was administered at a dose of 0.4 μg/kg intraperitoneally. Animals from LPS + MetS group received a 20 % fructose solution as the only source of drinking water and were administered LPS. In 10 % tissue homogenate of rat heart we studied: total activity of NO-synthases (NOS), activity of constitutive (cNOS) and inducible (iNOS) isoforms, activity of nitrate (NaR) and nitrite (NiR) reductases, concentration of peroxynitrites (ONOO-), nitrites, nitrosothiols and hydrogen sulfide.
Results. Combination of MetS and stimulation of organism with LPS led to increase in total NOS activity by 32.72 % compared to control group. Activity of cNOS did not change compared to control group. Activity of iNOS increased by 33.76 %. Arginase activity decreased by 23.53 %. NaR activity and NiR activity were increased by 86.67 % and by 149.29 %, respectively. Combination of MetS and stimulation of organism with LPS led to decrease in nitrite and nitrosothiols concentration by 38.73 % and by 54.79 %, respectively. Under these conditions concentration of ONOOelevated by 398.0 % compared to control group. Concentration of H S decreased by 27.56 %.
Conclusions. Combination of metabolic syndrome and stimulation of organism with bacterial lipopolysaccharide leads to prevalence of peroxynitrite formation during increased nitric oxide production NO-synthase-dependent and nitrate-nitrite-NO pathways in rat heart.
References
Infante T, Costa D, Napoli C. Novel Insights Regarding Nitric Oxide and Cardiovascular Diseases. Angiology. 2021;72(5):411-25. doi: 10.1177/0003319720979243
Hancock JT, Veal D. Nitric oxide, other reactive signalling compounds, redox, and reductive stress. J Exp Bot. 2021;72(3):819-29. doi: 10.1093/ jxb/eraa331
Kemp-Harper BK, Velagic A, Paolocci N, Horowitz JD, Ritchie RH. Cardiovascular Therapeutic Potential of the Redox Siblings, Nitric Oxide (NO•) and Nitroxyl (HNO), in the Setting of Reactive Oxygen Species Dysregulation. Handb Exp Pharmacol. 2021;264:311-37. doi: 10.1007/164_2020_389
Yassaghi Y, Jeddi S, Yousefzadeh N, Kashfi K, Ghasemi A. Long-term inorganic nitrate administration protects against myocardial ischemia-reperfusion injury in female rats. BMC Cardiovasc Disord. 2023;23(1):411. doi: 10.1186/s12872-023-03425-2
Ferguson SK, Woessner MN, Holmes MJ, Belbis MD, Carlström M, Weitzberg E, et al. Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure. J Appl Physiol (1985). 2021;130(4):914-22. doi: 10.1152/japplphysiol.00780.2020
Satoh T, Wang L, Espinosa-Diez C, Wang B, Hahn SA, Noda K, et al. Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction. Circulation. 2021;144(8):615-37. doi: 10.1161/CIRCULATIONA- HA.121.053889
Carlström M. Nitric oxide signalling in kidney regulation and cardiometabolic health. Nat Rev Nephrol. 2021;17(9):575-90. doi: 10.1038/s41581-021- 00429-z
Koka S, Xi L, Kukreja RC. Chronic inhibition of phosphodiesterase 5 with tadalafil affords cardioprotection in a mouse model of metabolic syndrome: role of nitric oxide. Mol Cell Biochem. 2020;468(1-2):47-58. doi: 10.1007/ s11010-020-03710-0
Lin Y, Xu Y, Zhang Z. Sepsis-Induced Myocardial Dysfunction (SIMD): the Pathophysiological Mechanisms and Therapeutic Strategies Targeting Mitochondria. Inflammation. 2020;43(4):1184-200. doi: 10.1007/s10753- 020-01233-w
Wu TD, Fawzy A, Brigham E, McCormack MC, Rosas I, Villareal DT, et al. Association of Triglyceride-Glucose Index and Lung Health: A Population-Based Study. Chest. 2021;160(3):1026-34. doi: 10.1016/j. chest.2021.03.056
Mamikutty N, Thent ZC, Sapri SR, Sahruddin NN, Mohd Yusof MR, Haji Suhaimi F. The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. Biomed Res Int. 2014;2014:263897. doi: 10.1155/2014/263897
Yelins’ka AM, Akimov OYe, Kostenko VO. Role of AP-1 transcriptional factor in development of oxidative and nitrosative stress in periodontal tissues during systemic inflammatory response. Ukr Biochem J. 2019;91(1):80-5. doi: 10.15407/ubj91.01.080
Akimov OYe, Mykytenko AO, Kostenko VO. Nitric oxide cycle activity in rat biceps femoris muscle under conditions of bacterial lipopolysaccharide influence, experimental metabolic syndrome and their combination. Ukr Biochem J. 2023;95(4):24-34. doi: 10.15407/ubj95.04.024
Mykytenko AO, Akimov OY, Neporada KS. Influence of lipopolysaccharide on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication. Fiziol Zh. 2022;68(2):29-35. doi: 10.15407/fz68.02.029
Şaman E, Cebova M, Barta A, Koneracka M, Zavisova V, Eckstein-Andicsova A, et al. Combined Therapy with Simvastatinand Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome. Int J Mol Sci. 2022;24(1):276. doi: 10.3390/ijms24010276
Mahdi A, Kövamees O, Pernow J. Improvement in endothelial function in cardiovascular disease – Is arginase the target? Int J Cardiol. 2020;301:20714. doi: 10.1016/j.ijcard.2019.11.004
Mahdi A, Tengbom J, Alvarsson M, Wernly B, Zhou Z, Pernow J. Red Blood Cell Peroxynitrite Causes Endothelial Dysfunction in Type 2 Diabetes Mellitus via Arginase. Cells. 2020;9(7):1712. doi: 10.3390/ cells9071712
Pérez-Torres I, Manzano-Pech L, Rubio-Ruíz ME, Soto ME, Guarner-Lans V. Nitrosative Stress and Its Association with Cardiometabolic Disorders. Molecules. 2020;25(11):2555. doi: 10.3390/molecules25112555
Yang Z, Su W, Zhang Y, Zhou L, Xia ZY, Lei S. Selective inhibition of PKCβ2 improves Caveolin-3/eNOS signaling and attenuates lipopolysaccharide-induced injury by inhibiting autophagy in H9C2 cardiomyocytes. J Mol Histol. 2021;52(4):705-15. doi: 10.1007/s10735-021-09990-0
Luo R, Chen X, Ma H, Yao C, Liu M, Tao J, et al. Myocardial caspase-3 and NF-κB activation promotes calpain-induced septic apoptosis: The role of Akt/eNOS/NO pathway. Life Sci. 2019;222:195-202. doi: 10.1016/j. lfs.2019.02.048
Peng Z, Zhang M, Ouyang M, Ouyang X, Xu G, Zhou J, et al. Protective effects of myocardium-targeted nanoparticles loaded L-arginineon on sepsis-induced myocardial injury. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020;32(8):953-9. doi: 10.3760/cma.j.cn121430-20200217-00168
Liu L, Guo H, Song A, Huang J, Zhang Y, Jin S, et al. Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways. BMC Immunol. 2020;21(1):32. doi: 10.1186/s12865-020-00355-y
Russo S, Kwiatkowski M, Govorukhina N, Bischoff R, Melgert BN. Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity: The Importance of Metabolites. Front Immunol. 2021;12:746151. doi: 10.3389/fimmu.2021.746151
Atawia RT, Bunch KL, Toque HA, Caldwell RB, Caldwell RW. Mechanisms of obesity-induced metabolic and vascular dysfunctions. Front Biosci (Landmark Ed). 2019;24(5):890-934. doi: 10.2741/4758
Schiffer TA, Lundberg JO, Weitzberg E, Carlström M. Modulation of mitochondria and NADPH oxidase function by the nitrate-nitrite-NO pathway in metabolic disease with focus on type 2 diabetes. Biochim Biophys Acta Mol Basis Dis. 2020;1866(8):165811. doi: 10.1016/j.bbadis.2020.165811
Fujishima Y, Kita S, Nishizawa H, Maeda N, Shimomura I. Cardiovascular significance of adipose-derived adiponectin and liver-derived xanthine oxidoreductase in metabolic syndrome. Endocr J. 2023;70(7):663-75. doi: 10.1507/endocrj.EJ23-0160
Li H, Zhang C, Zhang H, Li H. Xanthine oxidoreductase promotes the progression of colitis-associated colorectal cancer by causing DNA damage and mediating macrophage M1 polarization. Eur J Pharmacol. 2021;906:174270. doi: 10.1016/j.ejphar.2021.174270
Yang Y, Li S, Qu Y, Wang X, An W, Li Z, et al. Nitrate partially inhibits lipopolysaccharide-induced inflammation by maintaining mitochondrial function. J Int Med Res. 2020;48(2):300060520902605. doi: 10.1177/0300060520902605
Mykytenko A, Akimov O, Shevchenko O, Neporada K. Role of sulfide anion in the development of chronic alcoholic hepatitis under the conditions of modulation of adenosine monophosphate kinase – a correlational study. Eur J Clin Exp Med. 2023;21(3):567-75. doi: 10.15584/ejcem.2023.3.24
Magierowska K, Korbut E, Wójcik-Grzybek D, Bakalarz D, Sliwowski Z, Cieszkowski J, et al. Mitochondria-targeted hydrogen sulfide donors versus acute oxidative gastric mucosal injury. J Control Release. 2022;348:321-34. doi: 10.1016/j.jconrel.2022.05.051
Mykytenko AO, Akimov OYe, Yeroshenko GA, Neporada KS. Influence of NF -κB on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication. Ukr Biochem J. 2022;94(6):57-66. doi: 10.15407/ubj94.06.057
Akimov OY, Kostenko VO. Role of NF-κB transcriptional factor activation during chronic fluoride intoxication in development of oxidative-nitrosative stress in rat’s gastric mucosa. J Trace Elem Med Biol. 2020;61:126535. doi: 10.1016/j.jtemb.2020.126535
Wang L, Meng J, Wang C, Wang Y, Yang C, Li Y. Hydrogen sulfide attenuates cigarette smokeinduced pyroptosis through the TLR4/NF-κB signaling pathway. Int J Mol Med. 2022;49(5):56.doi: 10.3892/ijmm.2022.5112
Zhao M, Cheng Y, Wang X, Cui X, Cheng X, Fu Q, et al. Hydrogen Sulfide Attenuates High-Fat Diet-Induced Obesity: Involvement of mTOR/IKK/NFκB Signaling Pathway. Mol Neurobiol. 2022;59(11):6903-17. doi: 10.1007/ s12035-022-03004-0
Skrypnyk I, Maslova G, Lymanets T, Gusachenko I. L-arginine is an effective medication for prevention of endothelial dysfunction, a predictor of anthracycline cardiotoxicity in patients with acute leukemia. Exp Oncol. 2017;39(4):308-11.
Kostenko V, Akimov O, Gutnik O, Kostenko H, Kostenko V, Romantseva T, et al. Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response. Heliyon. 2023;9(5):e15551. doi: 10.1016/j.heliyon.2023.e15551
