Zamzam Water Mitigates Cardiac Toxicity Risk through Modulation of GUT Microbiota and the Renin-angiotensin System


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Abstract

Background:Cardiovascular diseases (CVDs) continue to exert a substantial global influence in specific areas due to population growth, aging, microbiota, and genetic/environmental factors. Drinking water has a strong impact on the health of an individual. Further, emerging evidence has highlighted the therapeutic potential and benefits of Zamzam water (Zam).

Objective:We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions.

Methods:Male rats were categorized into four groups: Group 1 as Normal control (NC), Group 2 as Zamzam control (ZC), Group 3 Disease control (DC) and Group 4 as Therapeutic control (DZ) treated with Zam against doxorubicin-induced disease at a dose of 1mg/kg boy weight) intraperitoneally (i.p).

Results:Significant dysbiosis in the composition of GM was observed in the DC group along with a significant decrease (p < 0.05) in serum levels of Zinc, interleukin-10 (IL-10), IL-6 and Angiotensin II (Ang II), while C-reactive protein (CRP), fibrinogen, and CKMB increased significantly (restoration of Zinc ions (0.72 ± 0.07 mcg/mL) compared to NC. Treatment with Zamzam exhibited a marked abundance of 18-times to 72% in Romboutsia, a genus of firmicutes, along with lowering of Proteobacteria in DZ followed by significant restoration of Zinc ions (0.72 ± 0.07 mcg/mL), significant (p ˂ 0.05) reduction in CRP (7.22 ± 0.39 mg/dL), CKMB (118.8 ± 1.02 U/L) and Fibrinogen (3.18 ± 0.16 mg/dL), significant (p < 0.05) increase in IL-10 (7.22 ± 0.84 pg/mL) and IL-6 (7.18 ± 0.40 pg/ml), restoration of Ang II (18.62 ± 0.50 nmol/mL/min), marked increase in renin with normal myocyte architecture and tissue orientation of kidney, and restoration of histological architecture of hepatocyte.

Conclusion:Zam treatment mitigated cardiac toxicity risk through the modulation of GUT microbiota and the renin-angiotensin system and tissue histology effectively.

About the authors

Firoz Anwar

Department of Biochemistry, Faculty of Science,, King Abdulaziz University

Author for correspondence.
Email: info@benthamscience.net

Ryan Sheikh

Department of Biochemistry, Faculty of Science, King Abdulaziz University

Email: info@benthamscience.net

Mohammad Nadem

Department of Biochemistry, Faculty of Science,, King Abdulaziz University

Email: info@benthamscience.net

Turky Asar

Department of Biology, College of Science and Arts at Alkamil, University of Jeddah

Email: info@benthamscience.net

Mohammed Almujtaba

Department of Biochemistry, Faculty of Science,, King Abdulaziz University

Email: info@benthamscience.net

Salma Naqvi

Department of Biomedical Sciences, College of Medicine, Gulf Medical University

Email: info@benthamscience.net

Fahad Al-Abbasi

Department of Biochemistry, Faculty of Science,, King Abdulaziz University

Email: info@benthamscience.net

Naif Abdullah Almalki

Department of Biochemistry, Faculty of Science,, King Abdulaziz University

Email: info@benthamscience.net

Vikas Kumar

Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences

Email: info@benthamscience.net

References

  1. Sagheer U, Al-Kindi S, Abohashem S, et al. Environmental pollution and cardiovascular disease: Part 1 of 2: Air pollution. JACC: Adv 2024; 3(2): 100805.
  2. Banks WA. A spectrum of topics for 2019: Advances in neuroinflammation, oxidative stress, obesity, diabetes mellitus, cardiovascular disease, autism, exosomes, and central nervous system diseases. Curr Pharm Des 2020; 26(1): 1-5. doi: 10.2174/138161282601200225102049 PMID: 32122292
  3. Almujtaba MA, Asar TO, Naqvi S, et al. Zinc in alkaline water (Zamzam) ameliorates doxorubicin induced cardiac remodeling. Pakistan J Zool 2022; 54(6): 2591-601.
  4. Youssef GA. Microbiological quality and physciochemical parameters of Alexandria drinking water and Zamzam water. J Pure Appl Microbiol 2016; 10(2): 1147-59.
  5. Agudosi ES, Abdullah EC, Mubarak NM, et al. Pilot study of in-line continuous flocculation water treatment plant. J Environ Chem Eng 2018; 6(6): 7185-91. doi: 10.1016/j.jece.2018.11.001
  6. Wu Y, Li J, Zhang X, et al. The distinct phases of fresh-seawater mixing intricately regulate the nitrogen transformation processes in a high run-off estuary: Insight from multi-isotopes and microbial function analysis. Water Res 2023; 247: 120809. doi: 10.1016/j.watres.2023.120809 PMID: 37922637
  7. Rechenburg A. Water & risk. 2019. Available from: https://www.ukbonn.de/site/assets/files/16444/water_and_risk_vol28_low.pdf
  8. Diwan A, Harke SN, Panche A. Microbiome of Finfish and Shellfish. Springer 2023; pp. 255-94. doi: 10.1007/978-981-99-0852-3_12
  9. Dias MF, Reis MP, Acurcio LB, et al. Changes in mouse gut bacterial community in response to different types of drinking water. Water Res 2018; 132: 79-89. doi: 10.1016/j.watres.2017.12.052 PMID: 29306702
  10. Taymaz-Nikerel H, Karabekmez ME, Eraslan S. Kırdar B. Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells. Sci Rep 2018; 8(1): 13672. doi: 10.1038/s41598-018-31939-9 PMID: 30209405
  11. Kalyanaraman B. Teaching the basics of the mechanism of doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree? Redox Biol 2020; 29: 101394. doi: 10.1016/j.redox.2019.101394 PMID: 31790851
  12. Yarmohammadi F, Rezaee R, Karimi G. Natural compounds against doxorubicin-induced cardiotoxicity: A review on the involvement of Nrf2/ARE signaling pathway. Phytother Res 2021; 35(3): 1163-75. doi: 10.1002/ptr.6882 PMID: 32985744
  13. Wenningmann N, Knapp M, Ande A, Vaidya TR, Ait-Oudhia S. Insights into doxorubicin-induced cardiotoxicity: Molecular mechanisms, preventive strategies, and early monitoring. Mol Pharmacol 2019; 96(2): 219-32. doi: 10.1124/mol.119.115725 PMID: 31164387
  14. Vanhaecke T, Bretin O, Poirel M, Tap J. Drinking water source and intake are associated with distinct gut microbiota signatures in US and UK populations. J Nutr 2022; 152(1): 171-82. doi: 10.1093/jn/nxab312 PMID: 34642755
  15. Mahmoud HS, Eltahlawi RA, Jan AA, et al. Zamzam water is pathogen-free, uricosuric, hypolipidemic and exerts tissue-protective effects: Relieving BBC concerns. Am J Blood Res 2020; 10(6): 386-96. PMID: 33489448
  16. Yu X, Huang L, Zhao J, et al. The relationship between serum zinc level and heart failure: A meta-analysis. Biomed Res Int 2018; 2018: 2739014. doi: 10.1155/2018/2739014
  17. Diao H, Yan J, Li S, et al. Effects of dietary zinc sources on growth performance and gut health of weaned piglets. Front Microbiol 2021; 12: 771617. doi: 10.3389/fmicb.2021.771617 PMID: 34858378
  18. Khalid N, Ahmad A, Khalid S, Ahmed A, Irfan M. Mineral composition and health functionality of Zamzam water: A review. Int J Food Prop 2014; 17(3): 661-77. doi: 10.1080/10942912.2012.660721
  19. El Maleky W, Mahfoz AM, Osman AO, Latif AEHA. Investigation of the impacts of zamzam water on streptozotocin-induced diabetic nephropathy in rats. In-vivo and in-vitro study. Biomed Pharmacother 2021; 138: 111474. doi: 10.1016/j.biopha.2021.111474 PMID: 33773466
  20. Bamosa AO, Badar A, Salahuddin M, Meheithif AA. Effect of Zamzam water on blood methemoglobin level in young rats. J Family Community Med 2019; 26(1): 30-5. doi: 10.4103/jfcm.JFCM_21_18 PMID: 30697102
  21. AlNouri DM. The concentration of selected ions in bottled, commercial zamzam, and household water in Riyadh city and its effect on bone mineral content in growing rabbits. Prog Nutr 2019; 21(2): 458-66.
  22. Skalny AV, Aschner M, Lei XG, et al. Gut microbiota as a mediator of essential and toxic effects of zinc in the intestines and other tissues. Int J Mol Sci 2021; 22(23): 13074. doi: 10.3390/ijms222313074 PMID: 34884881
  23. Sofi MH, Gudi R, Melethil KS, Perez N, Johnson BM, Vasu C. pH of drinking water influences the composition of gut microbiome and type 1 diabetes incidence. Diabetes 2014; 63(2): 632-44. doi: 10.2337/db13-0981 PMID: 24194504
  24. Wolf KJ, Daft JG, Tanner SM, Hartmann R, Khafipour E, Lorenz RG. Consumption of acidic water alters the gut microbiome and decreases the risk of diabetes in NOD mice. J Histochem Cytochem 2014; 62(4): 237-50. doi: 10.1369/0022155413519650 PMID: 24453191
  25. Chai L, Song Y, Chen A, Jiang L, Deng H. Gut microbiota perturbations during larval stages in Bufo gargarizans tadpoles after Cu exposure with or without the presence of Pb. Environ Pollut 2024; 340(Pt 2): 122774. doi: 10.1016/j.envpol.2023.122774 PMID: 37871736
  26. Prasad AS. Zinc is an antioxidant and anti-inflammatory agent: Its role in human health. Front Nutr 2014; 1: 14. doi: 10.3389/fnut.2014.00014 PMID: 25988117
  27. Bao B, Prasad AS, Beck FWJ, et al. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: A potential implication of zinc as an atheroprotective agent. Am J Clin Nutr 2010; 91(6): 1634-41. doi: 10.3945/ajcn.2009.28836 PMID: 20427734
  28. Tubek S, Grzanka P, Tubek I. Role of zinc in hemostasis: A review. Biol Trace Elem Res 2008; 121(1): 1-8. doi: 10.1007/s12011-007-8038-y PMID: 17968515
  29. Hung HM, Chen MF, Lee HF, Wang HL. Exploration of inflammatory biomarkers and psychological cardiovascular disease risk factors among community dwelling adults: A gender comparison study. Biol Res Nurs 2024; 26(1): 139-49. doi: 10.1177/10998004231197845 PMID: 37603875
  30. Chen Y, Meng P, Cheng S, et al. Assessing the effect of interaction between C-reactive protein and gut microbiome on the risks of anxiety and depression. Mol Brain 2021; 14(1): 133. doi: 10.1186/s13041-021-00843-1 PMID: 34481527
  31. Carlini V, Noonan DM, Abdalalem E, et al. The multifaceted nature of IL-10: Regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions. Front Immunol 2023; 14: 1161067. doi: 10.3389/fimmu.2023.1161067 PMID: 37359549
  32. Naqvi S, Asar TO, Kumar V, et al. A cross-talk between gut microbiome, salt and hypertension. Biomed Pharmacother 2021; 134: 111156. doi: 10.1016/j.biopha.2020.111156 PMID: 33401080
  33. Tang WHW, Li DY, Hazen SL. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol 2019; 16(3): 137-54. doi: 10.1038/s41569-018-0108-7 PMID: 30410105
  34. Kaczmarek A, Brinkman BM, Heyndrickx L, Vandenabeele P, Krysko DV. Severity of doxorubicin-induced small intestinal mucositis is regulated by the TLR-2 and TLR-9 pathways. J Pathol 2012; 226(4): 598-608. doi: 10.1002/path.3009 PMID: 21960132
  35. Xu XW, Song CC, Tan XY, Zhong CC, Luo Z. Effects of dietary zinc (Zn) levels on growth performance, nutrient composition, muscle development, antioxidant and inflammatory responses in yellow catfish muscle. Aquacult Rep 2023; 31: 101640. doi: 10.1016/j.aqrep.2023.101640
  36. Short WD, Rae M, Lu T, et al. Endogenous interleukin-10 contributes to wound healing and regulates tissue repair. J Surg Res 2023; 285: 26-34. doi: 10.1016/j.jss.2022.12.004 PMID: 36640607
  37. Islam T, Schulte AK, Ramalingam L, et al. Anti-inflammatory mechanisms of polyphenols in adipose tissue: Role of gut microbiota, intestinal barrier integrity and zinc homeostasis. J Nutr Biochem 2023; 115: 109242. doi: 10.1016/j.jnutbio.2022.109242 PMID: 36442715
  38. Hasan RA, Koh AY, Zia A. The gut microbiome and thromboembolism. Thromb Res 2020; 189: 77-87. doi: 10.1016/j.thromres.2020.03.003 PMID: 32192995
  39. Kryczka KE, Kruk M, Demkow M, Lubiszewska B. Fibrinogen and a triad of thrombosis, inflammation, and the renin-angiotensin system in premature coronary artery disease in women: A new insight into sex-related differences in the pathogenesis of the disease. Biomolecules 2021; 11(7): 1036. doi: 10.3390/biom11071036 PMID: 34356659
  40. Mitra S, Drautz-Moses DI, Alhede M, et al. In silico analyses of metagenomes from human atherosclerotic plaque samples. Microbiome 2015; 3(1): 38. doi: 10.1186/s40168-015-0100-y PMID: 26334731
  41. Jonsson AL, Bäckhed F. Role of gut microbiota in atherosclerosis. Nat Rev Cardiol 2017; 14(2): 79-87. doi: 10.1038/nrcardio.2016.183 PMID: 27905479
  42. Anwar F, Alhayyani S, Al-Abbasi FA, Nadeem MS, Kumar V. Pharmacological role of Vitamin C in stress-induced cardiac dysfunction via alteration in Gut microbiota. J Biochem Mol Toxicol 2022; 36(4): e22986. doi: 10.1002/jbt.22986 PMID: 35279900
  43. Tantisattamo E, Zadeh KK. Diet and hypertension. In: Hypertension. Elsevier 2024; pp. 17-48. doi: 10.1016/B978-0-323-88369-6.00002-5
  44. Peng X, Du J, Wang Y. Metabolic signatures in post-myocardial infarction heart failure, including insights into prediction, intervention, and prognosis. Biomed Pharmacother 2024; 170: 116079. doi: 10.1016/j.biopha.2023.116079 PMID: 38150879
  45. Jaworska K, Koper M, Ufnal M. Gut microbiota and renin-angiotensin system: A complex interplay at local and systemic levels. Am J Physiol Gastrointest Liver Physiol 2021; 321(4): G355-66. doi: 10.1152/ajpgi.00099.2021 PMID: 34405730
  46. Shu C, Huang J, Yang G, et al. Multi-omics reveals the attenuation of metabolic cardiomyopathy in mice by alkaloids in extracts from Clausena lansium (Lour.) via the transition of gastrointestinal microbiota to an alternative homeostasis. J Funct Foods 2024; 112: 105946. doi: 10.1016/j.jff.2023.105946
  47. Degraeve AL, Bindels LB, Haufroid V, et al. Tacrolimus pharmacokinetics is associated with gut microbiota diversity in kidney transplant patients: Results from a pilot cross-sectional study. Clin Pharmacol Ther 2024; 115(1): 104-15. doi: 10.1002/cpt.3077 PMID: 37846607
  48. Costa CFFA, Maia SB, Araujo R, et al. Gut microbiome and organ fibrosis. Nutrients 2022; 14(2): 352. doi: 10.3390/nu14020352 PMID: 35057530

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