Attenuation of Bleomycin-induced Toxicity on Selected Respiratory Function Metrics in Rabbits by a Polyherbal Preparation

Authors

  • Kennedy I. Amagon Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Kakjing D. Falang Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Bukata B. Bukar Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Jacob A. Kolawole Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Ukpe Ajima Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • James G. Damen Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Yusuf Agabi Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Richard J. Kutshik Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Ishaya Y. Longdet Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Simji Gomerep Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Ismaila Shittu Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Stephen D. Davou Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.
  • Noel N. Wannang Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

DOI:

https://doi.org/10.51412/psnnjp.2024.07

Keywords:

Bleomycin, Lung function, Polyherbal preparation, Toxicity
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Abstract

Introduction: Bleomycin, a commonly used chemotherapeutic agent, is known for its potential to induce respiratory toxicity. Despite its efficacy in treating various cancers, its use is limited by adverse effects, including pulmonary complications. These respiratory disorders and diseases can significantly impact an individual's quality of life, leading to various health complications.

Objective: The study assessed the effect of a polyherbal preparation (CoV Pla-2 extract) on tidal volume (V ), vital capacity (VC), inspiratory capacity (IC) and inspiratory reserve volume (IRV) T following bleomycin-induced lung injury in rabbits.

Methods: Lung injury was induced in rabbits using bleomycin administered via oropharyngeal aspiration. Animals were randomly divided into six groups of three rabbits each and received treatments as follows: Group 1: Normal Saline (5 ml/kg); Group 2: Bleomycin (4 U/kg); Group 3: CoV Pla-2 extract (125 mg/kg) and Bleomycin (4 U/kg); Group 4: CoV Pla-2 extract (500 mg/kg) and Bleomycin (4 U/kg); Group 5: CoV Pla-2 extract (125 mg/kg); Group 6: CoV Pla-2 extract (500mg/kg). Normal saline and the extract were administered daily for 14 days per oral, while Bleomycin was administered on days 0 and 2. Adigital spirometer was used to monitor some pulmonary function parameters.

Results: Results showed that administration of bleomycin decreased Inspiratory Capacity, Vital Capacity, Inspiratory Reserve Volume and Tidal Volume when compared to control. Coadministration of the extract and bleomycin caused an increase in these pulmonary function parameters, when compared to the animals administered bleomycin alone. Conclusion: The findings from this study suggest that CoV Pla-2 extract can modify bleomycin-induced lung injury, as seen in increase in Tidal Volume, Vital Capacity, Inspiratory capacity and Inspiratory Reserve Volume following injury due to bleomycin.

Author Biographies

Kennedy I. Amagon, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Jos, Nigeria.

Kakjing D. Falang, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Jos, Nigeria.

Bukata B. Bukar, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Jos, Nigeria.

Jacob A. Kolawole, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Pharmaceutical & Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Jos,
Nigeria.

Ukpe Ajima, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Pharmaceutical & Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Jos,
Nigeria.

James G. Damen, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, University of Jos,
Nigeria.

Yusuf Agabi, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Virology Unit, Department of Microbiology, Faculty of Natural Sciences, University of Jos, Nigeria.

Richard J. Kutshik, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Biochemistry, Faculty of Basic Medical Sciences, University of Jos, Nigeria.

Ishaya Y. Longdet, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Biochemistry, Faculty of Basic Medical Sciences, University of Jos, Nigeria.

Simji Gomerep, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Infectious Diseases Unit, Department of Medicine, Faculty of Clinical Sciences, University of Jos, Nigeria

Ismaila Shittu, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

National Veterinary Research Institute, Vom, Plateau State, Nigeria.

Stephen D. Davou, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Plateau State Ministry of Health, Jos, Plateau State, Nigeria.

Noel N. Wannang, Plateau State Research Team on Covid-19 and Other Infectious Diseases, Jos, Plateau State, Nigeria.

Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Jos, Nigeria.

References

Barnes PJ, Drazen JM, Rennard SI, Thomson NC (eds). Asthma and COPD: Basic mechanisms and clinical management. 2nd edn. London: Academic Press, 2009. Chpter 39, 471-93.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical

characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descrIptive study. Lancet. 2020 Feb

;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

Hosseini S, Imenshahidi M, Hosseinzadeh H, Karimi G. Effects of plant extracts and bioactive compounds on attenuation of bleomycin-induced pulmonary fibrosis. Biomed Pharmacother. 2018 Nov; 107: 1454 - 1465. doi:10.1016/j.biopha.2018.08.111. Epub 2018 Sep 3.

Yang W, Pan L, Cheng Y, Wu X, Huang S, Du J, Zhu H, Zhang M, Zhang Y. Amifostine attenuates bleomycin-induced pulmonary fibrosis in mice through inhibition of the PI3K/Akt/mTOR signaling pathway. Sci Rep. 2023 Jun 28;13(1):10485. doi: 10.1038/s41598-023-34060-8.

Albano GD, Gagliardo RP, Montalbano AM, Profita M. Overview of the Mechanisms of Oxidative Stress: Impact in Inflammation of the

Airway Diseases. Antioxidants (Basel). 2022 Nov 13;11(11):2237. doi: 10.3390/antiox11112237.

Hemmati AA, Jalali A, Keshavarz P. Effect of Chamomile Hydroalcoholic Extract on Bleomycin-Induced Pulmonary Fibrosis in Rat.

Tanaffos. 2018 Oct; 17(4): 264–271.

Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L152-60. doi:

1152/ajplung.00313.2007. Epub 2007 Nov 9.

Organ L, Bacci B, Koumoundouros E, Barcham G, Kimpton W, Nowell CJ, Samuel C, Snibson K. A novel segmental challenge model for

bleomycin-induced pulmonary fibrosis in sheep. Exp Lung Res. 2015 Apr;41(3):115-34. doi: 10.3109/01902148.2014.985806. Epub 2014 Dec

Hua X, Xu Y, Liu G, Sun L, Zhang H, Pan Q, Liu D, Li B. An Experimental Model of Anterior Urethral Stricture in Rabbits With Local

Injections of Bleomycin. Urology. 2018 Jun; 116: 230. e9-230. e15.doi:10.1016/j.urology.2017.12.031. Epub 2018 Mar 12.

Parasuraman S, Thing GS, Dhanaraj SA. Polyherbal formulation: Concept of ayurveda. Pharmacogn Rev. 2014 Jul;8(16):73-80. doi:

4103/0973-7847.134229.

Sharma A, Bachheti A, Sharma P, Bachheti RK, Husen A(2020) Phytochemistry, pharmacological activities, nanoparticle fabrication, commercial products and waste utilization of Carica papaya L.: a comprehensive review. Current Research in Biotechnology 2020; 2: 145 - 60. https://doi.org/10.1016/j.crbiot.2020.11.001

Tijjani MA, Mohammed GT, Alkali YT, Adamu TB, Abdurahaman FI. Phytochemical analysis, analgesic and antipyretic properties of ethanolic leaf extract of Vernonia amygdalina Del. J Herbmed Pharmacol. 2017;6(3): 95-99.

Ibulubo MT, Eze GI, Ozolua RI, Baxter-Grillo D, Uwaya DO. Evaluation of the protective and ameliorative properties of Garcinia kola on

histamine-induced bronchoconstriction in guinea pigs. Pharmacognosy Res. 2012 Oct;4(4):203-7. doi: 10.4103/0974-8490.102262.

Izam YY, Aguiyi JC. Effects of Carissa Edulis leaf extract on haematological Parameters of CCL4 induced albino rats. Nigerian Journal of Pharmacy 2021; 55(1): 20 - 2 . https://doi.org/10.51412/psnnjp.2021.4

Ya'u J, Malami S, Abdullahi SB, Yaro AH. Analgesic and Anti-inflammatory Activities of the Residual Aqueous Fraction of Carissa edulis Root Bark (Vahl) in Experimental Animals. African Journal of Pharmacology and Therapeutics 2017;6(4): 173-77.

Al-Youssef H, Hassan WHB. Phytochemical and Biological Studies of the Aerial Parts of Carissa edulis Growing in Saudi Arabia. Biomed

Pharmacol J 2012; 5(1): 9 - 1 8 . https://doi.org/10.13005/bpj/314

Chang JS, Wang KC, Yeh CF, Shieh DE, Chiang LC. Fresh ginger (Zingiber officinale) has antiviral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol. 2013 Jan 9;145(1):146-51. doi: 10.1016/j.jep.2012.10.043. Epub 2012 Nov 1.

Townsend EA, Siviski ME, Zhang Y, Xu C, Hoonjan B, Emala CW. Effects of ginger and its constituents on airway smooth muscle relaxation and calcium regulation. Am J Respir Cell Mol Biol. 2013 Feb; 48(2): 157 - 63. doi: 10.1165/rcmb.2012-0231OC. Epub 2012 Oct 11.

Nigam M., Atanassova M., Mishra A. P., et al. Bioactive compounds and health benefits of Artemisia species. Natural Product Communications. 2019; 14(7) doi: 10. 1177/1934578x19850354. https://doi.org/10.1177/1934578X19850354

Kshirsagar SG, Rao RV. Antiviral and Immunomodulation Effects of Artemisia. Medicina (Kaunas). 2021 Feb 27;57(3):217. doi: 10.3390/medicina57030217.

National Research Council: A Guide for the Care and Use of Laboratory Animals. In: A Report of the Institute of Laboratory Animal Resources Committee on Care and Use of Laboratory Animals. National Institutes of Health, National Academy Press, Washington. 2011. https://www.ncbi.nlm.nih.gov/books/NBK54050/. Access ed September 20, 2023. doi: 10.17226/12910.

Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2008 Sep;295(3):L379-99. doi: 10.1152/ajplung.00010.2008. Epub 2008 Jul 11.

Bale S, Sunkoju M, Reddy SS, Swamy V, Godugu C. Oropharyngeal aspiration of bleomycin: An alternative experimental model of pulmonary fibrosis developed in Swiss mice. Indian J Pharmacol. 2016 Nov-Dec;48(6):643-648. doi: 10.4103/0253-7613.194859.

De Vooght V, Vanoirbeek JA, Haenen S, Verbeken E, Nemery B, Hoet PH. Oropharyngeal aspiration: an alternative route for challenging in a mouse model of chemical-induced asthma. Toxicology. 2009 May 2; 259(1-2): 84 - 9. doi: 10.1016/j.tox.2009.02.007. Epub 2009 Feb 28.

Gilhodes JC, Julé Y, Kreuz S, Stierstorfer B, Stiller D, Wollin L. Quantification of Pulmonary Fibrosis in a Bleomycin Mouse Model Using Automated Histological Image Analysis. PLoS One. 2017 Jan 20;12(1):e0170561. doi: 10.1371/journal.pone.0170561.

Milton PL, Dickinson H, Jenkin G, Lim R. Assessment of respiratory physiology of C57BL/6mice following bleomycin

administration using barometric plethysmography. Respiration. 2012;83(3):253-66. doi: 10.1159/000330586. Epub 2011 Oct 11.

Patil N, Paulose RM, Udupa KS, Ramakrishna N, Ahmed T. Pulmonary Toxicity of Bleomycin - ACase Series from a Tertiary Care Center in Southern India. J Clin Diagn Res. 2016 Apr; 10(4): FR01 - 3. doi: 10.7860/JCDR/2016/18773.7626. Epub 2016 Apr 1.

Poursalehi HR, Samareh Fekri M, Sharifi Far F, Mandegari A, Izadi A, Mahmoodi R, Nematollahi H, Porgholamhosein F, Ghorani V, Samareh Fekri M. Early and late preventive effect of Nigella sativa on the bleomycin-induced pulmonary fibrosis in rats: An experimental study. Avicenna J Phytomed. 2018 May-Jun;8(3):263-275.

Gabazza EC, Kasper M, Ohta K, Keane M, D'Alessandro-Gabazza C, Fujimoto H, Nishii Y, Nakahara H, Takagi T, Menon AG, Adachi Y,

Suzuki K, Taguchi O. Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse. Pathol Int. 2004 Oct;54(10):774-80. doi: 10.1111/j.1440-1827.2004.01754.x.

Schmidt R, Ruppert C, Markart P, Lübke N, Ermert L, Weissmann N, Breithecker A, Ermert M, Seeger W, Günther A. Changes in pulmonary surfactant function and composition in bleomycin-induced pneumonitis and fibrosis. Toxicol Appl Pharmacol. 2004 Mar 1;195(2):218-31. doi: 10.1016/j.taap.2003.11.011.

Katsuma S, Nishi K, Tanigawara K, Ikawa H, Shiojima S, Takagaki K, Kaminishi Y, Suzuki Y, Hirasawa A, Ohgi T, Yano J, Murakami Y,

Tsujimoto G. Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNAmicroarray-based gene expression profiling.

Biochem Biophys Res Commun. 2001 Nov 9;288(4):747-51. doi: 10.1006/bbrc.2001.5853.

Mcelroy M, Lam C, Cranston I, Baily J, Aston P, Nandi M, Milne A. Use of Telemetry and Plethysmography to Assess Respiratory Function in Conscious Rats with Bleomycin-Induced Lung Fibrosis. European Respiratory Journal Sep 2019, 54 (suppl 63): PA 2418.

https://doi.org/10.1183/13993003.congress2019.PA2418

Li H, Hao Y, Zhang H, Ying W, Li D, Ge Y, Ying B, Cheng B, Lian Q, Jin S Posttreatment with Protectin DX ameliorates bleomycin-induced

pulmonary fibrosis and lung dysfunction in mice. Sci Rep 2017; 7: 46754. https://doi.org/10.1038/srep46754

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Published

2024-04-30

How to Cite

Amagon, K. I., Falang, K. D., Bukar, B. B., Kolawole, J. A., Ajima, U., Damen, J. G., … Wannang, N. N. (2024). Attenuation of Bleomycin-induced Toxicity on Selected Respiratory Function Metrics in Rabbits by a Polyherbal Preparation. The Nigerian Journal of Pharmacy, 58(1), 59–67. https://doi.org/10.51412/psnnjp.2024.07