O3FA ALLEVIATES INFLAMMATION IN CHALLENGED ANIMAL MODELS AND EXERTS INHIBITORY EFFECT ON LEUKOCYTE DIFFERENTIAL PARAMETERS IN CARRAGEENAN-INDUCED PERITONITIS

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O3FA ALLEVIATES INFLAMMATION IN CHALLENGED ANIMAL MODELS AND EXERTS INHIBITORY EFFECT ON LEUKOCYTE DIFFERENTIAL PARAMETERS IN CARRAGEENAN-INDUCED PERITONITIS

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Author(s): Aminu Omale ¹ ^, , Jamila Audu Omale ² , Samuel Attah Egu ¹

Publication date (Electronic preprint): 27 April 2024

Journal: ScienceOpen Preprints

Publisher: ScienceOpen

Keywords: Inflammation, Carrageenan, Peritonitis, Leukocytes, O3FA, Neutrophil

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Abstract

Introduction : Anti-inflammatory action of dietary omega-3-polyunsaturated fatty acid (O3FA) supplementation in animal models was studied using standard methods. The therapeutic safety of anti-inflammatory supplements utilizing natural forms, such as omega -3 fatty acids (n-3 fatty acids), is important in addition to its effectiveness. Methods: The nutritional intervention of omega-3 fish oil extract in experimental animals for acute inflammatory models was investigated using standard methods (Carrageenan, Arachidonic acid, and Prostaglandin E2 analyses). Total leukocyte count and differential parameters in carrageenan-induced peritonitis were also determined by standard methods. Results: Results obtained demonstrated a notable reduction in inflammation caused by the O3FA. For groups 1, 2, 3, 4, and 5, the percentage inhibition of the carrageenan-induced paw oedema after 24 hours was 78.57 %, 57.14 %, 50.00 %, 100.00 % and 92.85 %, respectively. Arachidonic acid-induced ear oedema percentage inhibition was 30, 24, 27, 37, and 40 %, while the PGE-2 test showed inhibition of by 44.16, 52.48, 61.34, 74, and 80.05 %. The novelty of the work is demonstrated in the use of dietary supplements as anti- inflammatory compounds as opposed to the usual non- steroidal anti-inflammatories. The results also show O3FA exerting an inhibitory effect on leukocyte parameters. As the dose of the extract increased, there was a trend of decreasing total leukocyte count. The groups administered with a 20mg dose of celecoxib (5.6 ± 0.23 x 10 ³) and a combination of 300mg O3FA with 20mg celecoxib (5.9 ± 0.18 x 10 ³) exhibited the lowest overall leukocyte count, notably lacking statistically significant variance. Conclusion: This outcome underscores the extract's heightened inhibitory impact on leukocyte migration amid peritonitis. Inhibition of carrageenan-induced peritonitis was 26.47, 18.63, 30.39, 42.16 and 45.09 %. The control group showed an ANC of 6.74 x 10 ³/µL, an ALC of 3.09 x 10 ³/µL, and an AMXD of 0.37 x 10 ³/µL. Absolute Neutrophil Count (ANC) for all the treatment groups fall between 3080 - 6740µl which is within the acceptable limit of 2500 - 7000µl for ANC. Also, for ALC, which is 2300 - 3090µl from the table has an acceptable limit of 1000 - 5000µl while that for MXD from the table is from 220 - 370µl which is well within the limit of 200 – 1090µl acceptability.

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Title: ScienceOpen Preprints

Publisher: ScienceOpen

Publication date (Electronic preprint): 27 April 2024

Affiliations

[1 ] Department of Pure & Industrial Chemistry, Kogi State University Anyigba Nigeria;

[2 ] Department of Biochemistry, Kogi State University Anyigba Nigeria;

Author notes

[* ]Email: omale.a@ 123456ksu.edu.ng .

Author information

Aminu Omale https://orcid.org/0000-0001-8867-5915

Jamila Audu Omale https://orcid.org/0000-0003-0517-4897

Samuel Attah Egu https://orcid.org/0000-0003-1636-6528

Article

DOI: 10.14293/PR2199.000833.v1

SO-VID: 446e6489-0835-42d6-86b4-e1fd61cf8d7b

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This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

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Date received : 27 April 2024

References

Layé Sophie, Nadjar Agnès, Joffre Corinne, Bazinet Richard P.. Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology. Pharmacological Reviews. Vol. 70(1):12–38. 2018. American Society for Pharmacology & Experimental Therapeutics (ASPET). [Cross Ref]
Skorepa Pavel, Sobotka Ondrej, Vanek Jan, Ticha Alena, Fortunato Joao, Manak Jan, Blaha Vladimir, Horacek Jan M., Sobotka Lubos. The Impact of Glucose-Based or Lipid-Based Total Parenteral Nutrition on the Free Fatty Acids Profile in Critically Ill Patients. Nutrients. Vol. 12(5)2020. MDPI AG. [Cross Ref]
Calder Philip C.. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochemical Society Transactions. Vol. 45(5):1105–1115. 2017. Portland Press Ltd. [Cross Ref]
Calder Philip C.. n-3 PUFA and inflammation: from membrane to nucleus and from bench to bedside. Proceedings of the Nutrition Society. Vol. 79(4):404–416. 2020. Cambridge University Press (CUP). [Cross Ref]
Alberti Gigliola, Gana Juan Cristóbal, Santos José L.. Fructose, Omega 3 Fatty Acids, and Vitamin E: Involvement in Pediatric Non-Alcoholic Fatty Liver Disease. Nutrients. Vol. 12(11)2020. MDPI AG. [Cross Ref]
Romay C., Ledón N., González R.. Further studies on anti-inflammatory activity of phycocyanin in some animal models of inflammation. Inflammation Research. Vol. 47(8):334–338. 1998. Springer Science and Business Media LLC. [Cross Ref]
Saito-Sasaki Natsuko, Sawada Yu, Nakamura Motonobu. Maresin-1 and Inflammatory Disease. International Journal of Molecular Sciences. Vol. 23(3)2022. MDPI AG. [Cross Ref]
Serhan Charles N., Levy Bruce D.. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. Journal of Clinical Investigation. Vol. 128(7):2657–2669. 2018. American Society for Clinical Investigation. [Cross Ref]
Serhan Charles N.. Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Molecular Aspects of Medicine. Vol. 58:1–11. 2017. Elsevier BV. [Cross Ref]
Shao W., Ebaid R., El-Sheekh M., Abomohra A., Eladel H.. Pharmaceutical applications and consequent environmental impacts of Spirulina (Arthrospira): An overview. Grasas y Aceites. Vol. 70(1)2019. Editorial CSIC. [Cross Ref]
D'Addona Alessio, Maffulli Nicola, Formisano Silvestro, Rosa Donato. Inflammation in tendinopathy. The Surgeon. Vol. 15(5):297–302. 2017. Elsevier BV. [Cross Ref]
Zainul Azlan Nurhazirah, Abd Ghafar Norzana, Mohd Yusof Yasmin Anum, Makpol Suzana. Toxicity study of Chlorella vulgaris water extract on female Sprague Dawley rats by using the Organization for Economic Cooperation and Development (OECD) Guideline 420. Journal of Applied Phycology. Vol. 32(5):3063–3075. 2020. Springer Science and Business Media LLC. [Cross Ref]
Borham Layla E., Mahfoz Amal M., Ibrahim Ibrahim A.A., Shahzad Naiyer, ALrefai Abeer Ahmed, Labib Amira A., Bin Sef Bassam, Alshareef Abdulrahmman, Khan Meshal, Milibary Ali, Al Ghamdi Saeed. The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine-induced epileptic disorders in Wistar rats. Brain Research. Vol. 1648:418–424. 2016. Elsevier BV. [Cross Ref]
Chen Qun, Wei Wei. Effects and mechanisms of melatonin on inflammatory and immune responses of adjuvant arthritis rat. International Immunopharmacology. Vol. 2(10):1443–1449. 2002. Elsevier BV. [Cross Ref]
Annamalai Parvathi, Thangam Elden Berla. Local and Systemic Profiles of Inflammatory Cytokines in Carrageenan-induced Paw Inflammation in Rats. Immunological Investigations. Vol. 46(3):274–283. 2017. Informa UK Limited. [Cross Ref]
Meshram Girish Gulab, Kumar Anil, Rizvi Waseem, Tripathi C.D., Khan R.A.. Evaluation of the anti-inflammatory activity of the aqueous and ethanolic extracts of the leaves of Albizzia lebbeck in rats. Journal of Traditional and Complementary Medicine. Vol. 6(2):172–175. 2016. Elsevier BV. [Cross Ref]
López-Vicario Cristina, Rius Bibiana, Alcaraz-Quiles José, García-Alonso Verónica, Lopategi Aritz, Titos Esther, Clària Joan. Pro-resolving mediators produced from EPA and DHA: Overview of the pathways involved and their mechanisms in metabolic syndrome and related liver diseases. European Journal of Pharmacology. Vol. 785:133–143. 2016. Elsevier BV. [Cross Ref]
Mantzioris Evangeline, Cleland Leslie G, Gibson Robert A, Neumann Mark A, Demasi Maryanne, James Michael J. Biochemical effects of a diet containing foods enriched with n−3 fatty acids. The American Journal of Clinical Nutrition. Vol. 72(1):42–48. 2000. Elsevier BV. [Cross Ref]
Kasahara Yoshimasa, Hikino Hiroshi, Tsurufuji Susumu, Watanabe Masako, Ohuchi Kazuo. Antiinflammatory Actions of Ephedrines in Acute Inflammations. Planta Medica. Vol. 51(04):325–331. 1985. Georg Thieme Verlag KG. [Cross Ref]
Gutiérrez Saray, Svahn Sara L, Johansson Maria E. Effects of Omega-3 Fatty Acids on Immune Cells. International Journal of Molecular Sciences. Vol. 20(20)2019. MDPI AG. [Cross Ref]
Ferrándiz M. L., Alcaraz M. J.. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents and Actions. Vol. 32(3-4):283–288. 1991. Springer Science and Business Media LLC. [Cross Ref]
Tsuda H, Nishimura H, Sawada T, Takatsuki K. The roles of lymph node stromal cells in proliferation of lymphoid leukaemia cells. British Journal of Cancer. Vol. 61(3):362–364. 1990. Springer Science and Business Media LLC. [Cross Ref]
Fleming Chérina, Russcher Henk, Lindemans Jan, de Jonge Robert. Clinical relevance and contemporary methods for counting blood cells in body fluids suspected of inflammatory disease. Clinical Chemistry and Laboratory Medicine (CCLM). Vol. 53(11)2015. Walter de Gruyter GmbH. [Cross Ref]
Sreeja Puthanpura Sasidharan, Arunachalam Karuppusamy, Martins Domingos Tabajara de Oliveira, Lima Joaquim Corsino da Silva, Balogun Sikiru Olaitan, Pavan Eduarda, Saikumar Sathyanarayanan, Dhivya Sivaraj, Kasipandi Muniyandi, Parimelazhagan Thangaraj. Sphenodesme involucrata var. paniculata (C.B. Clarke) Munir.: Chemical characterization, anti-nociceptive and anti-inflammatory activities of methanol extract of leaves. Journal of Ethnopharmacology. Vol. 225:71–80. 2018. Elsevier BV. [Cross Ref]
Tvedten Harold, Raskin Rose E.. Leukocyte DisordersSmall Animal Clinical Diagnosis by Laboratory Methods. p. 63–91. 2012. Elsevier. [Cross Ref]
Brugnara Carlo, Jo Hipp Mary, Irving Patricia J., Lathrop Hazel, Lee Patricia A., Minchello Elaine M., Winkelman James. Automated Reticulocyte Counting and Measurement of Reticulocyte Cellular Indices:Evaluation of the Miles H*3 Blood Analyzer. American Journal of Clinical Pathology. Vol. 102(5):623–632. 1994. Oxford University Press (OUP). [Cross Ref]
Xu Youchun, Xie Xinwu, Duan Yong, Wang Lei, Cheng Zhen, Cheng Jing. A review of impedance measurements of whole cells. Biosensors and Bioelectronics. Vol. 77:824–836. 2016. Elsevier BV. [Cross Ref]
Koca U, Toker G, Akkol EK. Assessment of the Extracts of Centaurea tchihatcheffii Fischer for Anti-inflammatory and Analgesic Activities in Animal Models. Tropical Journal of Pharmaceutical Research. Vol. 8(3)2009. African Journals Online (AJOL). [Cross Ref]
Christie William W., Harwood John L.. Oxidation of polyunsaturated fatty acids to produce lipid mediators. Essays in Biochemistry. Vol. 64(3):401–421. 2020. Portland Press Ltd. [Cross Ref]
Ling Victoria, Zabetakis Ioannis. The Role of an Anti-Inflammatory Diet in Conjunction to COVID-19. Diseases. Vol. 9(4)2021. MDPI AG. [Cross Ref]
Pisaniello Anthony D., Psaltis Peter J., King Peta M., Liu Ge, Gibson Robert A., Tan Joanne TM., Duong MyNgan, Nguyen Tracy, Bursill Christina A., Worthley Matthew I., Nicholls Stephen J., Di Bartolo Belinda A.. Omega-3 fatty acids ameliorate vascular inflammation: A rationale for their atheroprotective effects. Atherosclerosis. Vol. 324:27–37. 2021. Elsevier BV. [Cross Ref]
Shah Anoop Dinesh, Denaxas Spiros, Nicholas Owen, Hingorani Aroon D., Hemingway Harry. Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases. Journal of the American College of Cardiology. Vol. 69(9):1160–1169. 2017. Elsevier BV. [Cross Ref]
Forget Patrice, Khalifa Céline, Defour Jean-Philippe, Latinne Dominique, Van Pel Marie-Cécile, De Kock Marc. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Research Notes. Vol. 10(1)2017. Springer Science and Business Media LLC. [Cross Ref]
Tecchio Cristina, Cassatella Marco Antonio. Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation. Cellular & Molecular Immunology. Vol. 18(4):905–918. 2021. Springer Science and Business Media LLC. [Cross Ref]
Greenlee-Wacker Mallary C., Kremserová Silvie, Nauseef William M.. Lysis of human neutrophils by community-associated methicillin-resistant Staphylococcus aureus. Blood. Vol. 129(24):3237–3244. 2017. American Society of Hematology. [Cross Ref]
Mishalian Inbal, Granot Zvi, Fridlender Zvi G.. The diversity of circulating neutrophils in cancer. Immunobiology. Vol. 222(1):82–88. 2017. Elsevier BV. [Cross Ref]
J. A Omale,, L. U. S Ezeanyika,, A Omale,. Membrane Stabilization and Vascular Permeability as Mechanisms for the Evaluation of Anti-inflammatory Action of Omega-3-poly Unsaturated Fatty Acid Oil Extract. Current Nutrition & Food Science. Vol. 19:2023. Bentham Science Publishers Ltd. [Cross Ref]
Jamila. A Omale, Lawrence US Ezeanyika, Bennett C Nwanguma, Aminu Omale. Effect of dietary omega-3-polyunsaturated fatty acid in animal models of experimentally-induced granulomatous inflammatio. Magna Scientia Advanced Biology and Pharmacy. Vol. 8(2):13–18. 2023. GSC Online Press. [Cross Ref]

Comments

Comment on this article

[1] Layé Sophie, Nadjar Agnès, Joffre Corinne, Bazinet Richard P.. Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology. Pharmacological Reviews. Vol. 70(1):12–38. 2018. American Society for Pharmacology & Experimental Therapeutics (ASPET). [Cross Ref]

[2] Skorepa Pavel, Sobotka Ondrej, Vanek Jan, Ticha Alena, Fortunato Joao, Manak Jan, Blaha Vladimir, Horacek Jan M., Sobotka Lubos. The Impact of Glucose-Based or Lipid-Based Total Parenteral Nutrition on the Free Fatty Acids Profile in Critically Ill Patients. Nutrients. Vol. 12(5)2020. MDPI AG. [Cross Ref]

[3] Calder Philip C.. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochemical Society Transactions. Vol. 45(5):1105–1115. 2017. Portland Press Ltd. [Cross Ref]

[4] Calder Philip C.. <i>n</i>-3 PUFA and inflammation: from membrane to nucleus and from bench to bedside. Proceedings of the Nutrition Society. Vol. 79(4):404–416. 2020. Cambridge University Press (CUP). [Cross Ref]

[5] Alberti Gigliola, Gana Juan Cristóbal, Santos José L.. Fructose, Omega 3 Fatty Acids, and Vitamin E: Involvement in Pediatric Non-Alcoholic Fatty Liver Disease. Nutrients. Vol. 12(11)2020. MDPI AG. [Cross Ref]

[6] Romay C., Ledón N., González R.. Further studies on anti-inflammatory activity of phycocyanin in some animal models of inflammation. Inflammation Research. Vol. 47(8):334–338. 1998. Springer Science and Business Media LLC. [Cross Ref]

[7] Saito-Sasaki Natsuko, Sawada Yu, Nakamura Motonobu. Maresin-1 and Inflammatory Disease. International Journal of Molecular Sciences. Vol. 23(3)2022. MDPI AG. [Cross Ref]

[8] Serhan Charles N., Levy Bruce D.. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. Journal of Clinical Investigation. Vol. 128(7):2657–2669. 2018. American Society for Clinical Investigation. [Cross Ref]

[9] Serhan Charles N.. Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Molecular Aspects of Medicine. Vol. 58:1–11. 2017. Elsevier BV. [Cross Ref]

[10] Shao W., Ebaid R., El-Sheekh M., Abomohra A., Eladel H.. Pharmaceutical applications and consequent environmental impacts of <em>Spirulina (Arthrospira)</em>: An overview. Grasas y Aceites. Vol. 70(1)2019. Editorial CSIC. [Cross Ref]

[11] D'Addona Alessio, Maffulli Nicola, Formisano Silvestro, Rosa Donato. Inflammation in tendinopathy. The Surgeon. Vol. 15(5):297–302. 2017. Elsevier BV. [Cross Ref]

[12] Zainul Azlan Nurhazirah, Abd Ghafar Norzana, Mohd Yusof Yasmin Anum, Makpol Suzana. Toxicity study of Chlorella vulgaris water extract on female Sprague Dawley rats by using the Organization for Economic Cooperation and Development (OECD) Guideline 420. Journal of Applied Phycology. Vol. 32(5):3063–3075. 2020. Springer Science and Business Media LLC. [Cross Ref]

[13] Borham Layla E., Mahfoz Amal M., Ibrahim Ibrahim A.A., Shahzad Naiyer, ALrefai Abeer Ahmed, Labib Amira A., Bin Sef Bassam, Alshareef Abdulrahmman, Khan Meshal, Milibary Ali, Al Ghamdi Saeed. The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine-induced epileptic disorders in Wistar rats. Brain Research. Vol. 1648:418–424. 2016. Elsevier BV. [Cross Ref]

[14] Chen Qun, Wei Wei. Effects and mechanisms of melatonin on inflammatory and immune responses of adjuvant arthritis rat. International Immunopharmacology. Vol. 2(10):1443–1449. 2002. Elsevier BV. [Cross Ref]

[15] Annamalai Parvathi, Thangam Elden Berla. Local and Systemic Profiles of Inflammatory Cytokines in Carrageenan-induced Paw Inflammation in Rats. Immunological Investigations. Vol. 46(3):274–283. 2017. Informa UK Limited. [Cross Ref]

[16] Meshram Girish Gulab, Kumar Anil, Rizvi Waseem, Tripathi C.D., Khan R.A.. Evaluation of the anti-inflammatory activity of the aqueous and ethanolic extracts of the leaves of Albizzia lebbeck in rats. Journal of Traditional and Complementary Medicine. Vol. 6(2):172–175. 2016. Elsevier BV. [Cross Ref]

[17] López-Vicario Cristina, Rius Bibiana, Alcaraz-Quiles José, García-Alonso Verónica, Lopategi Aritz, Titos Esther, Clària Joan. Pro-resolving mediators produced from EPA and DHA: Overview of the pathways involved and their mechanisms in metabolic syndrome and related liver diseases. European Journal of Pharmacology. Vol. 785:133–143. 2016. Elsevier BV. [Cross Ref]

[18] Mantzioris Evangeline, Cleland Leslie G, Gibson Robert A, Neumann Mark A, Demasi Maryanne, James Michael J. Biochemical effects of a diet containing foods enriched with n−3 fatty acids. The American Journal of Clinical Nutrition. Vol. 72(1):42–48. 2000. Elsevier BV. [Cross Ref]

[19] Kasahara Yoshimasa, Hikino Hiroshi, Tsurufuji Susumu, Watanabe Masako, Ohuchi Kazuo. Antiinflammatory Actions of Ephedrines in Acute Inflammations. Planta Medica. Vol. 51(04):325–331. 1985. Georg Thieme Verlag KG. [Cross Ref]

[20] Gutiérrez Saray, Svahn Sara L, Johansson Maria E. Effects of Omega-3 Fatty Acids on Immune Cells. International Journal of Molecular Sciences. Vol. 20(20)2019. MDPI AG. [Cross Ref]

[21] Ferrándiz M. L., Alcaraz M. J.. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents and Actions. Vol. 32(3-4):283–288. 1991. Springer Science and Business Media LLC. [Cross Ref]

[22] Tsuda H, Nishimura H, Sawada T, Takatsuki K. The roles of lymph node stromal cells in proliferation of lymphoid leukaemia cells. British Journal of Cancer. Vol. 61(3):362–364. 1990. Springer Science and Business Media LLC. [Cross Ref]

[23] Fleming Chérina, Russcher Henk, Lindemans Jan, de Jonge Robert. Clinical relevance and contemporary methods for counting blood cells in body fluids suspected of inflammatory disease. Clinical Chemistry and Laboratory Medicine (CCLM). Vol. 53(11)2015. Walter de Gruyter GmbH. [Cross Ref]

[24] Sreeja Puthanpura Sasidharan, Arunachalam Karuppusamy, Martins Domingos Tabajara de Oliveira, Lima Joaquim Corsino da Silva, Balogun Sikiru Olaitan, Pavan Eduarda, Saikumar Sathyanarayanan, Dhivya Sivaraj, Kasipandi Muniyandi, Parimelazhagan Thangaraj. Sphenodesme involucrata var. paniculata (C.B. Clarke) Munir.: Chemical characterization, anti-nociceptive and anti-inflammatory activities of methanol extract of leaves. Journal of Ethnopharmacology. Vol. 225:71–80. 2018. Elsevier BV. [Cross Ref]

[25] Tvedten Harold, Raskin Rose E.. Leukocyte DisordersSmall Animal Clinical Diagnosis by Laboratory Methods. p. 63–91. 2012. Elsevier. [Cross Ref]

[26] Brugnara Carlo, Jo Hipp Mary, Irving Patricia J., Lathrop Hazel, Lee Patricia A., Minchello Elaine M., Winkelman James. Automated Reticulocyte Counting and Measurement of Reticulocyte Cellular Indices:<i>Evaluation of the Miles H*3 Blood Analyzer</i>. American Journal of Clinical Pathology. Vol. 102(5):623–632. 1994. Oxford University Press (OUP). [Cross Ref]

[27] Xu Youchun, Xie Xinwu, Duan Yong, Wang Lei, Cheng Zhen, Cheng Jing. A review of impedance measurements of whole cells. Biosensors and Bioelectronics. Vol. 77:824–836. 2016. Elsevier BV. [Cross Ref]

[28] Koca U, Toker G, Akkol EK. Assessment of the Extracts of Centaurea tchihatcheffii Fischer for Anti-inflammatory and Analgesic Activities in Animal Models. Tropical Journal of Pharmaceutical Research. Vol. 8(3)2009. African Journals Online (AJOL). [Cross Ref]

[29] Christie William W., Harwood John L.. Oxidation of polyunsaturated fatty acids to produce lipid mediators. Essays in Biochemistry. Vol. 64(3):401–421. 2020. Portland Press Ltd. [Cross Ref]

[30] Ling Victoria, Zabetakis Ioannis. The Role of an Anti-Inflammatory Diet in Conjunction to COVID-19. Diseases. Vol. 9(4)2021. MDPI AG. [Cross Ref]

[31] Pisaniello Anthony D., Psaltis Peter J., King Peta M., Liu Ge, Gibson Robert A., Tan Joanne TM., Duong MyNgan, Nguyen Tracy, Bursill Christina A., Worthley Matthew I., Nicholls Stephen J., Di Bartolo Belinda A.. Omega-3 fatty acids ameliorate vascular inflammation: A rationale for their atheroprotective effects. Atherosclerosis. Vol. 324:27–37. 2021. Elsevier BV. [Cross Ref]

[32] Shah Anoop Dinesh, Denaxas Spiros, Nicholas Owen, Hingorani Aroon D., Hemingway Harry. Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases. Journal of the American College of Cardiology. Vol. 69(9):1160–1169. 2017. Elsevier BV. [Cross Ref]

[33] Forget Patrice, Khalifa Céline, Defour Jean-Philippe, Latinne Dominique, Van Pel Marie-Cécile, De Kock Marc. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Research Notes. Vol. 10(1)2017. Springer Science and Business Media LLC. [Cross Ref]

[34] Tecchio Cristina, Cassatella Marco Antonio. Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation. Cellular & Molecular Immunology. Vol. 18(4):905–918. 2021. Springer Science and Business Media LLC. [Cross Ref]

[35] Greenlee-Wacker Mallary C., Kremserová Silvie, Nauseef William M.. Lysis of human neutrophils by community-associated methicillin-resistant Staphylococcus aureus. Blood. Vol. 129(24):3237–3244. 2017. American Society of Hematology. [Cross Ref]

[36] Mishalian Inbal, Granot Zvi, Fridlender Zvi G.. The diversity of circulating neutrophils in cancer. Immunobiology. Vol. 222(1):82–88. 2017. Elsevier BV. [Cross Ref]

[37] J. A Omale,, L. U. S Ezeanyika,, A Omale,. Membrane Stabilization and Vascular Permeability as Mechanisms for the Evaluation of Anti-inflammatory Action of Omega-3-poly Unsaturated Fatty Acid Oil Extract. Current Nutrition & Food Science. Vol. 19:2023. Bentham Science Publishers Ltd. [Cross Ref]

[38] Jamila. A Omale, Lawrence US Ezeanyika, Bennett C Nwanguma, Aminu Omale. Effect of dietary omega-3-polyunsaturated fatty acid in animal models of experimentally-induced granulomatous inflammatio. Magna Scientia Advanced Biology and Pharmacy. Vol. 8(2):13–18. 2023. GSC Online Press. [Cross Ref]

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O3FA ALLEVIATES INFLAMMATION IN CHALLENGED ANIMAL MODELS AND EXERTS INHIBITORY EFFECT ON LEUKOCYTE DIFFERENTIAL PARAMETERS IN CARRAGEENAN-INDUCED PERITONITIS

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