Evaluation of the Level of Pro and Anti-Inflammatory Cytokines and Haematological Parameters in/Polyunsaturated Rich Fish-Oil-Treated Rats after Induction of Cardiac Ischemia with Isoprenaline
Deffo Tiepma Ngongang Eurydice Flore1*, Tebo Emeline Fri1, Arrey oben Ebob1, Achidi Aduni Ufuan1, Yolandia Jamea Nganje Epanty1, Tenyang Noel2, Agnes Namondo Mbongo Lyonga1 and Tiencheu Bernard1
1Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Cameroon
2Department of Biological Sciences, Faculty of Science, University of Maroua, Maroua, Cameroon
*Corresponding Author: Deffo Tiepma Ngongang Eurydice Flore, Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Cameroon.
Received:
August 25, 2025; Published: September 29, 2025
Abstract
Cardiovascular diseases (CVD), including cardiac ischemia; an imbalance between coronary blood supply and myocardial demand have emerged as a major public health problem and impose an escalating burden on the health care system in Cameroon. Moreover, anti-ischaemic medications only eliminate or reduce cardiac ischemia by decreasing myocardial oxygen demand, increasing myocardial oxygen supply, or both, but do not correct the underlying cause of ischemia (atherosclerosis). But dietary n-3 polyunsaturated fatty acids have positive effects on cardiovascular diseases, with mackerel fish being one of its rich source, due to the EPA and DHA it contains. The present study investigated the effects of pre-treatment with mackerel fish oil (FO), on the heart of the rat which is associated with the isoprenaline (ISO)-induced cardiac ischemia, since it is a rich source of n-3 polyunsaturated fatty acids. The study was conducted on 42 Wistar rats which were divided into seven groups of 6 rats each, and pre-treated as follows. The normal control (NO) received distilled water, negative control (NC), was only induced with isoprenaline, test groups 1 and 2 (8C and 10C), received cooked fish oil at doses of 8 and 10 ml/kg body weight, test groups 3 and 4 (8R and10R), received raw fish oil at doses of 8 and 10 ml/kg body weight, orally for 4 weeks and the positive control (PC) received propranolol (standard drug) 10 days before sacrifice. Acute myocardial ischemia was induced by isoprenaline (ISO, 85 mg/kg) twice, 48 and 24 hours before sacrifice. Eventually, the animals were sacrificed on day 29, after an overnight fast and samples collected for plasma cytokine levels and hematological parameter evaluation. Moreover, their growth response and exploratory behavior were also examined during the assay. Based on the results, ISO administration significantly increased the plasma levels of inflammatory cytokines and decreased haematological parameters compared to the normal control group. In addition, rats were less explorative in the open field, as their number of crossing and rearing decreased significantly from 67.3 to 19.7 and from 26.2 to 3.3 with a decreased weight due to loss of appetite following ISO administration. However, a remarkable decrease in plasma levels of TNF-α, IL-6, IL-1β, IL-10, and INF-γ was observed. Additionally, pre-treatment showed a significant restoration in the plasma levels of hematological parameters, including WBC count and its subtypes compared to the ISO group. In general, pre-treatment with FO significantly decreased plasma levels of inflammatory cytokines compared to the standard drug, with raw FO showing a better effect. Therefore, FO, especially oil from raw Scomber scrombrus results in preventing cardiac ischemia, and thus implies mackerel fish oil should be used as supplements source of omega fatty acids.
Keywords: Cardiac Ischemia; Mackerel Fish Oil; Isoprenaline; Hematological; Scomber Scrombrus; Exploratory Behavior; Cytokine
References
- Yusuf S., et al. “Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study”. The Lancet10226 (2020): 795-808.
- Cushman M., et al. “Ten-year differences in women’s awareness related to coronary heart disease: results of the 2019 American Heart Association National Survey: a special report from the American Heart Association”. Circulation7 (2021): e239-e248.
- Fathima SN. “An Update on Myocardial Infarction”. Current Research and Trends in Medical Science and Technology (2021): 1.
- Tibaut M., et al. “Pathophysiology of myocardial infarction and acute management strategies”. Cardiovascular and Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular and Hematological Agents)3 (2016): 150-159.
- Frangogiannis NG. “The inflammatory response in myocardial injury, repair, and remodelling”. Nature Reviews Cardiology5 (2014): 255-265.
- Huang S and NG Frangogiannis. “Anti‐inflammatory therapies in myocardial infarction: failures, hopes and challenges”. British Journal of Pharmacology9 (2018): 1377-1400.
- Muralidharan S and P Mandrekar. “Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation”. Journal of Leukocyte Biology6 (2013): 1167-1184.
- Nair A., et al. “Inflammation, symptoms, benefits, reaction, and biochemistry, in Inflammation and Natural Products”. Elsevier (2021): 1-19.
- Szade A., et al. “Cellular and molecular mechanisms of inflammation‐induced angiogenesis”. IUBMB life3 (2015): 145-159.
- Medzhitov R. “Origin and physiological roles of inflammation”. Nature7203 (2008): 428-435.
- Sherwood ER and T Toliver-Kinsky. “Mechanisms of the inflammatory response”. Best Practice and Research Clinical Anaesthesiology3 (200): 385-405.
- Duell BL., et al. “Recent insights into microbial triggers of interleukin-10 production in the host and the impact on infectious disease pathogenesis”. FEMS Immunology and Medical Microbiology 3 (2012): 295-313.
- Naldini A and F Carraro. “Role of inflammatory mediators in angiogenesis”. Current Drug Targets-Inflammation and Allergy1 (2005): 3-8.
- Ehlting C., et al. “Acute-phase protein synthesis: a key feature of innate immune functions of the liver”. Biological Chemistry9 (2021): 1129-1145.
- Bowry AD., et al. “The burden of cardiovascular disease in low-and middle-income countries: epidemiology and management”. Canadian Journal of Cardiology9 (2015): 1151-1159.
- Oliveira GMMd., et al. “Cardiovascular Statistics–Brazil 2021”. Arquivos Brasileiros De Cardiologia 118 (2018): 115-373.
- Ambrose JA and AS Bhullar. “Inflammation and thrombosis in coronary atherosclerosis: Pathophysiologic mechanisms and clinical correlations”. EMJ 1 (2019): 71-78.
- Endo J and M Arita. “Cardioprotective mechanism of omega-3 polyunsaturated fatty acids”. Journal of Cardiology1 (2016): 22-27.
- Oppedisano F., et al. “The anti-inflammatory and antioxidant properties of n-3 PUFAs: Their role in cardiovascular protection”. Biomedicines 9 (2020): 306.
- Wang J., et al. “Stability and stabilization of omega-3 oils: A review”. Trends in Food Science and Technology 118 (2021): 17-35.
- Chuo PH. “Differential expression of serum proteome of hypercholesterolemic rats following treatment with Ficus deltoidea/Chuo Peck Ham”. Universiti Malaya (2018).
- Sobot T., et al. “Effect of folic acid on isoprenaline-induced myocardial injury in rats”. Physiology International1 (2024): 80-96.
- Jensen SK. “Improved Bligh and Dyer extraction procedure”. Lipid Technology12 (2008): 280-281.
- Stephanie NKJ., et al. “Anxiolytic-like properties of Hallea ciliata in mice”. African Journal of Traditional, Complementary and Alternative Medicines4 (2016): 1-7.
- Gould TD., et al. “The open field test”. Mood and anxiety related phenotypes in mice: Characterization using behavioral tests (2009): 1-20.
- Stenberg K., et al. “Analytical performance of a canine ELISA monocyte chemoattractant protein-1 assay for use in cats and evaluation of circulating levels in normal weight and obese cats”. Acta veterinaria Scandinavica1 (2022): 22.
- Landmesser U., et al. “Effect of inclisiran, the small-interfering RNA against proprotein convertase subtilisin/kexin type 9, on platelets, immune cells, and immunological biomarkers: a pre-specified analysis from ORION-1”. Cardiovascular Research1 (2021): 284-291.
- Elmi M. “Investigating blood plasma levels of cytokines and amyloid-β as potential diagnostic biomarkers for preclinical Alzheimer’s disease”. Macquarie University (2022).
- Zahedi-Nejad MS. “Characterisation of the Expression and Degradation of the Pro-inflammatory Cytokine Interleukin 1”. The University of Manchester (United Kingdom) (2012).
- Revathikumar P., et al. “Immunomodulatory effects of nicotine on interleukin 1β activated human astrocytes and the role of cyclooxygenase 2 in the underlying mechanism”. Journal of Neuroinflammation 13 (2016): 1-13.
- Sharangi AB and S Das. “Healing indigestion: A phytotherapeutic review”. Advances in Traditional Medicine3 (2022): 437-453.
- Laiglesia-González LM. “Effects of Maresin 1, an omega-3 fatty acid-derived lipid mediator, on adipose tissue and liver function in obesity” (2017).
- Osborne V., et al. “Effects of supplementing fish oil in the drinking water of dairy cows on production performance and milk fatty acid composition”. Journal of Animal Science3 (2008): 720-729.
- Gan XT., et al. “Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat”. Circulation: Heart Failure3 (2014): 491-499.
- Seibenhener ML and MC Wooten. “Use of the open field maze to measure locomotor and anxiety-like behavior in mice”. JoVE (Journal of Visualized Experiments) 96 (2015): e52434.
- Deane KH., et al. “Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials”. The British Journal of Psychiatry 3 (2021): 135-142.
- Nakagawa Y., et al. “Effect of social isolation stress on saliva BDNF in rat”. Journal of Oral Science 4 (2019): 516-520.
- Huang M., et al. “Role of interleukin-6 in regulation of immune responses to remodeling after myocardial infarction”. Heart Failure Reviews 20 (2015): 25-38.
- Saxena A., et al. “IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium”. The Journal of Immunology9 (2013): 4838-4848.
- Frangogiannis NG. “Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts”. Discoveries1 (2015).
- McLennan PL. “Cardiac physiology and clinical efficacy of dietary fish oil clarified through cellular mechanisms of omega-3 polyunsaturated fatty acids”. European Journal of Applied Physiology 114 (2014): 1333-1356.
- Ali O and A Szabó. “Review of eukaryote cellular membrane lipid Composition, with special attention to the fatty acids”. International Journal of Molecular Sciences21 (2023): 15693.
- Ivary SHA., et al. “Effect of Fish and Flaxseed Oil Supplementation on Isoprenaline-Induced Myocardial Infarction in Rats: Inhibition of Mitochondrial Permeability Transition Pore Opening”. Crescent Journal of Medical and Biological Sciences2 (2019).
- Calder PC., et al. “Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition”. Ageing Research Reviews 40 (2017): 95-119.
- Li D. “Advances in Dietary Lipids and Human Health”. Academic Press (2022).
- Mukerjee S., et al. “Polyunsaturated fatty acids mediated regulation of membrane biochemistry and tumor cell membrane integrity”. Membranes7 (2021): 479.
- Bottaccioli F and AG Bottaccioli. “Psycho-neuro-endocrino-immunology paradigm and cardiovascular diseases”. Integrative Cardiology: A New Therapeutic Vision (2017): 139-151.
- Calder PC. “Eicosanoids”. Essays in Biochemistry3 (2020): 423-441.
- Li LY., et al. “Cardioprotective effects of omega 3 fatty acids from fish oil and it enhances autoimmunity in porcine cardiac myosin-induced myocarditis in the rat model”. Zeitschrift für Naturforschung C9-10 (2021): 407-415.
- Patterson III WL and PT Georgel. “Breaking the cycle: the role of omega-3 polyunsaturated fatty acids in inflammation-driven cancers”. Biochemistry and Cell Biology 5 (2014): 321-328.
- Wang YY., et al. “Association between hematological parameters and metabolic syndrome components in a Chinese population”. Journal of Diabetes and its Complications6 (2004): 322-327.
- Al-Dulaimi KAK., et al. “Classification of white blood cell types from microscope images: Techniques and challenges”. Microscopy science: Last approaches on educational programs and applied research (Microscopy Book Series 8 (2018): 17-25.
- Ahmad HI., et al. “Immune tolerance vs. immune resistance: the interaction between host and pathogens in infectious diseases”. Frontiers in Veterinary Science 9 (2022): 827407.
- McBurney MI., et al. “Lower omega-3 status associated with higher erythrocyte distribution width and neutrophil-lymphocyte ratio in UK Biobank cohort”. Prostaglandins Leukotrienes and Essential Fatty Acids 192 (2023): 102567.
- Harris WS., et al. “Comparative effects of an acute dose of fish oil on omega-3 fatty acid levels in red blood cells versus plasma: implications for clinical utility”. Journal of Clinical Lipidology 5 (2013): 433-440.
- McBurney MI., et al. “Omega-3 index is directly associated with a healthy red blood cell distribution width”. Prostaglandins, Leukotrienes and Essential Fatty Acids 176 (2022): 102376.
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