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Trypanosoma brucei brucei Induced Hypoglycaemia Depletes Hepatic Glycogen and Altered Hepatic Hexokinase and Glucokinase Activities in Infected Mice

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Abstract

Purpose

Little progress has been made in understanding the effect of Trypanosoma brucei brucei infection that was allowed to run its course without treatment on human and animal carbohydrate metabolism even though most of the symptoms associated with the disease can be clearly linked with interference with host energy generation. The present study therefore assessed the course of untreated Trypanosoma brucei brucei infection on hepatic glycogen, hepatic hexokinase and glucokinase activities.

Methods

Mice were grouped into two: control and infected group. Trypanosomiasis was induced by intraperitoneal inoculation of 1 × 104 parasites/mice in 0.3 ml of phosphate saline glucose. The infection was allowed to run its course until the first mortality was recorded with all the mice showing chronic symptoms of the second stage of the disease before the research was terminated. Blood and liver samples were collected from the mice in each group for the assessment of hepatic glycogen and total protein, hepatic hexokinase and glucokinase activities, liver biomarkers, blood glucose and protein with packed cell volume.

Results

The infection resulted in decrease in blood glucose, hepatic glycogen, liver protein, PCV, hepatic hexokinase and glucokinase activities, but increase in serum total protein and liver biomarkers.

Conclusion

Trypanosomiasis negatively affects hepatic integrity, resulting in the depletion of hepatic glycogen content and suppression of both hepatic hexokinase and glucokinase activities. The suppression of hepatic hexokinase and glucokinase activities suggested that trypanosomiasis affected the oxidation of glucose and host energy generation via glycolysis. This probably denied the host of the needed energy which is likely the reason for early death in untreated African trypanosomiasis.

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References

  1. Gudisa H, Kebede B, Terefe G, Tsegaye D (2016) A study on the effect of monomorphic Trypanosoma brucei rhodesiense, (Eatro 3 ET at 1.2) on experimentally infected goats and Swiss white mice. J Bacteriol Parasitol 7:2. https://doi.org/10.4172/2155-9597.1000287

    Article  CAS  Google Scholar 

  2. Pineda E, Thonnus M, Mazet M, Mourier A, Cahoreau E et al (2018) Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: analysis of metabolic adaptations on glycerol-rich conditions. PLoS Pathog 14:e1007412. https://doi.org/10.1371/journal.ppat.1007412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Moreno SA, Cantos GV (2018) The kinetic properties of hexokinases in African trypanosomes of the subgenus Trypanozoon match the blood glucose levels of mammal hosts. Comp Biochem Physiol B Biochem Mol Biol 217:51–59. https://doi.org/10.1016/j.cbpb.2017.12.014

    Article  CAS  PubMed  Google Scholar 

  4. Mwiinde AM, Simuunza M, Namangala B, Chama-Chiliba CM, Machila N et al (2017) Estimating the economic and social consequences for patients diagnosed with human African trypanosomiasis in Muchinga, Lusaka and Eastern Provinces of Zambia (2004–2014). Infect Dis Poverty 6:1–13. https://doi.org/10.1186/s40249-017-0363-6

    Article  Google Scholar 

  5. Ojo RJ, Enoch GA, Adeh FS, Fompun LC, Bitrus BY et al (2021) Comprehensive analysis of oral administration of Vitamin E on the early stage of Trypanosoma brucei brucei infection. J Parasit Dis. https://doi.org/10.1007/s12639-020-01322-5

    Article  PubMed  PubMed Central  Google Scholar 

  6. Adebayo AO, Ibitoroko G, Emechete E (2019) Effect of vitamin E on hydrogen peroxide and nitrogen levels in male wistar albinorats infected with Trypanosoma brucei brucei. Int J Biomed Adv Res 10:e4934. https://doi.org/10.7439/ijbar

    Article  CAS  Google Scholar 

  7. Edoga CO, Njoku OO, Okeke JJ, Ani C (2013) Effects of vitamin C treatment on serum protein, albumin, beta-globulin profiles and body weight of Trypanosoma brucei-infected Rattus Noregicus. Anim Res Int 10:1685–1688

    Google Scholar 

  8. Umar I, Ogenyi E, Okodaso D, Kimeng E, Stancheva G et al (2007) Amelioration of anaemia and organ damage by combined intraperitoneal administration of vitamins A and C to Trypanosoma brucei brucei-infected rats. Afr J Biotech. https://doi.org/10.5897/AJB2007.000-2322

    Article  Google Scholar 

  9. Vanwalleghem G, Morias Y, Beschin A, Szymkowski DE, Pays E (2017) Trypanosoma brucei growth control by TNF in mammalian host is independent of the soluble form of the cytokine. Sci Rep 7:6165–6165. https://doi.org/10.1038/s41598-017-06496-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Igbokwe I, Lafon J, Umar I, Hamidu I (1998) Erythrocyte and hepatic glutathione concentrations in acute Trypanosoma brucei infection of rats. Trop Vet Med 16:81–83

    Google Scholar 

  11. Ihedioha J, Anwa A (2002) Liver retinol and carotenoid concentration of rats experimentally infected with Trypanosoma brucei. Trop Vet 20:1–7. https://doi.org/10.4314/tv.v20i1.4501

    Article  Google Scholar 

  12. Umar I, Igbalajobi F, Toh Z, Gidado A, Shugaba A et al (2001) Effects of repeated daily doses of vitamin E. (alpha-tocopherol) on some biochemical indices of rats infected with T. bricei (Basa strain). W Afr J Biol Sci 12:1–7

    Google Scholar 

  13. Umar IA, Toh ZA, Igbalajobi FI, Gidado A, Buratai LB (2000) The role of vitamin C administration in alleviation of organ damage in rats infected with Trypanosoma brucei. J Clin Biochem Nutr 28:1–7. https://doi.org/10.3164/jcbn.28.1

    Article  CAS  Google Scholar 

  14. König M, Bulik S, Holzhütter H-G (2012) Quantifying the contribution of the liver to glucose homeostasis: a detailed kinetic model of human hepatic glucose metabolism. PLoS Comput Biol 8:e1002577. https://doi.org/10.1371/journal.pcbi.1002577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nuttall FQ, Ngo A, Gannon MC (2008) Regulation of hepatic glucose production and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant? Diabetes Metab Res Rev 24:438–458. https://doi.org/10.1002/dmrr.863

    Article  CAS  PubMed  Google Scholar 

  16. Radziuk J, Pye S (2001) Hepatic glucose uptake, gluconeogenesis and the regulation of glycogen synthesis. Diabetes Metab Res Rev 17:250–272. https://doi.org/10.1002/dmrr.217

    Article  CAS  PubMed  Google Scholar 

  17. Wahren J, Ekberg K (2007) Splanchnic regulation of glucose production. Annu Rev Nutr 27:329–345. https://doi.org/10.1146/annurev.nutr.27.061406.093806

    Article  CAS  PubMed  Google Scholar 

  18. Igbokwe I (1994) Mechanisms of cellular injury in African trypanosomiasis. Vet Bull 64:611–620

    Google Scholar 

  19. Bezie M, Girma M, Dagnachew S, Tadesse D, Tadesse G (2014) African trypanosomes: virulence factors, pathogenicity and host responses. J Vet Adv 4:732–745. https://doi.org/10.5455/jva.20141129012406

    Article  Google Scholar 

  20. Greenwood BM, Whittle HC (1980) The pathogenesis of sleeping sickness. Trans R Soc Trop Med Hyg 74:716–725. https://doi.org/10.1016/0035-9203(80)90184-4

    Article  CAS  PubMed  Google Scholar 

  21. Kennedy PG, Rodgers J (2019) Clinical and neuropathogenetic aspects of human African trypanosomiasis. Front Immunol. https://doi.org/10.3389/fimmu.2019.00039

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kristensson K, Bentivoglio M (1999) Pathology of African trypanosomiasis. In: Dumas M, Bouteille B, Buguet A (eds) Progress in human African trypanosomiasis, sleeping sickness. Springer Paris, Paris, pp 157–181. https://doi.org/10.1007/978-2-8178-0857-4_13

    Chapter  Google Scholar 

  23. Poltera A (1985) Pathology of human African trypanosomiasis with reference to experimental African trypanosomiasis and infections of the central nervous system. Br Med Bull 41:169–174. https://doi.org/10.1093/oxfordjournals.bmb.a072045

    Article  CAS  PubMed  Google Scholar 

  24. Sudarshi D, Lawrence S, Pickrell WO, Eligar V, Walters R et al (2014) Human African trypanosomiasis presenting at least 29 years after infection—what can this teach us about the pathogenesis and control of this neglected tropical disease? PLoS Negl Trop Dis 8:e3349. https://doi.org/10.1371/journal.pntd.0003349

    Article  PubMed  PubMed Central  Google Scholar 

  25. Creek DJ, Mazet M, Achcar F, Anderson J, Kim D-H et al (2015) Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose. PLoS Pathog 11:e1004689. https://doi.org/10.1371/journal.ppat.1004689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Coley AF, Dodson HC, Morris MT, Morris JC (2011) Glycolysis in the African trypanosome: targeting enzymes and their subcellular compartments for therapeutic development. Mol Biol Int. https://doi.org/10.4061/2011/123702

    Article  PubMed  PubMed Central  Google Scholar 

  27. Nwagwu M, Opperdoes F (1982) Regulation of glycolysis in Trypanosoma brucei: hexokinase and phosphofructokinase activity. Acta Trop 39:61–72. https://doi.org/10.5169/seals-312962

    Article  CAS  PubMed  Google Scholar 

  28. Moreno SA, Nava M (2015) Trypanosoma evansi is alike to Trypanosoma brucei brucei in the subcellular localisation of glycolytic enzymes. Mem Inst Oswaldo Cruz 110:468–475. https://doi.org/10.1590/0074-02760150024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mazet M, Morand P, Biran M, Bouyssou G, Courtois P et al (2013) Revisiting the central metabolism of the bloodstream forms of Trypanosoma brucei: production of acetate in the mitochondrion is essential for parasite viability. PLoS Negl Trop Dis 7:e2587. https://doi.org/10.1371/journal.pntd.0002587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rodgers J (2009) Human African trypanosomiasis, chemotherapy and CNS disease. J Neuroimmunol 211:16–22. https://doi.org/10.1016/j.jneuroim.2009.02.007

    Article  CAS  PubMed  Google Scholar 

  31. Ochei JO, Kolhatkar AA (2000) Medical laboratory science: theory and practice. McGraw Hill Education, New York

    Google Scholar 

  32. Murray M, Trail J, Turner D, Wissocq Y (1983) Livestock productivity and trypanotolerance. Network Trainning Manual, ILCA, pp 4–10

  33. Tack C, Pohlmeier H, Behnke T, Schmid V, Grenningloh M et al (2012) Accuracy evaluation of five blood glucose monitoring systems obtained from the pharmacy: a European multicenter study with 453 subjects. Diabetes Technol Ther 14:330–337. https://doi.org/10.1089/dia.2011.0170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Barham D, Trinder P (1972) An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst 97:142–145. https://doi.org/10.1039/AN9729700142

    Article  CAS  PubMed  Google Scholar 

  35. Carroll NV, Longley RW, Roe JH (1956) The determination of glycogen in liver and muscle by use of anthrone reagent. J biol Chem 220:583–593. https://doi.org/10.1016/S0021-9258(18)65284-6

    Article  CAS  PubMed  Google Scholar 

  36. Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63. https://doi.org/10.1093/ajcp/28.1.56

    Article  CAS  PubMed  Google Scholar 

  37. Bowers GN Jr, McComb RB (1975) Measurement of total alkaline phosphatase activity in humanserum. Clin Chem 21:1988–1995. https://doi.org/10.1093/clinchem/21.13.1988

    Article  CAS  PubMed  Google Scholar 

  38. van den Bergh AAH, Muller P (1916) Über eine direkte und eine indirekte Diazoreaktion auf Bilirubin. Biochem Ztschr 77:90

    Google Scholar 

  39. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1016/0003-2697(76)90527-3

    Article  CAS  PubMed  Google Scholar 

  40. Laurian R, Dementhon K, Doumèche B, Soulard A, Noel T et al (2019) Hexokinase and glucokinases are essential for fitness and virulence in the pathogenic yeast Candida albicans. Front Microbiol 10:327. https://doi.org/10.3389/fmicb.2019.00327

    Article  PubMed  PubMed Central  Google Scholar 

  41. Marciacq Y, Seed JR (1970) Reduced levels of glycogen and glucose-6-phosphatase in livers of guinea pigs infected with Trypanosoma gambiense. J Infect Dis. https://doi.org/10.1093/infdis/121.6.653

    Article  PubMed  Google Scholar 

  42. Seifert HS (1996) Tropical animal health. Springer Science and Business Media, Berlin

    Book  Google Scholar 

  43. Adeiza AA, Maikai VA, Lawal AI (2008) Comparative haematological changes in experimentally infected Savannah brown goats with Trypanosoma brucei and Trypanosoma vivax. Afr J Biotechnol 7(13):2295–2298

    Google Scholar 

  44. Magez S, Schwegmann A, Atkinson R, Claes F, Drennan M et al (2008) The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice. PLoS Pathog 4:e1000122. https://doi.org/10.1371/journal.ppat.1000122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hilali M, Abdel-Gawad A, Nassar A, Abdel-Wahab A (2006) Hematological and biochemical changes in water buffalo calves (Bubalus bubalis) infected with Trypanosoma evansi. Vet Parasitol 139:237–243. https://doi.org/10.1016/j.vetpar.2006.02.013

    Article  CAS  PubMed  Google Scholar 

  46. Ohaeri C, Eluwa M (2011) Abnormal biochemical and haematological indices in trypanosomiasis as a threat to herd production. Vet Parasitol 177:199–202. https://doi.org/10.1016/j.vetpar.2011.02.002

    Article  CAS  PubMed  Google Scholar 

  47. Bashir YA, Umar IA, Nok AJ (2012) Effects of methanol extract of Vernonia amygdalina leaf on survival and some biochemical parameters in acute Trypanosoma brucei brucei infection. Afr J Biochem Res 6:150–158

    Google Scholar 

  48. Rifkin MR, Landsberger FR (1990) Trypanosome variant surface glycoprotein transfer to target membranes: a model for the pathogenesis of trypanosomiasis. Proc Natl Acad Sci 87:801–805. https://doi.org/10.1073/pnas.87.2.801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Esievo K, Saror D, Ilemobade A, Hallaway M (1982) Variation in erythrocyte surface and free serum sialic acid concentrations during experimental Trypanosoma vivax infection in cattle. Res Vet Sci 32:1–5. https://doi.org/10.1016/S0034-5288(18)32427-5

    Article  CAS  PubMed  Google Scholar 

  50. Lonsdale-Eccles JD, Grab DJ (1987) Lysosomal and non-lysosomal peptidyl hydrolases of the bloodstream forms of Trypanosoma brucei brucei. Eur J Biochem 169:467–475. https://doi.org/10.1111/j.1432-1033.1987.tb13634.x

    Article  CAS  PubMed  Google Scholar 

  51. Amole B, Clarkson A Jr, Shear H (1982) Pathogenesis of anemia in Trypanosoma brucei-infected mice. Infect Immun 36:1060–1068. https://doi.org/10.1128/iai.36.3.1060-1068.1982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Basir R, Rahiman SF, Hasballah K, Chong W, Talib H et al (2012) Plasmodium berghei ANKA infection in ICR mice as a model of cerebral malaria. Iran J Parasitol 7:62–74

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Samuel S, Ayobami D, Jane A (2018) Comparative effects of commonly used artemisinin-based combination therapies (ACTs) on reproductive parameters in male Wistar rats. MOJ Bioequiv Bioavailab 5:113–119. https://doi.org/10.15406/mojbb.2018.05.00090

    Article  Google Scholar 

  54. Farombi EO, Olowu BI, Emerole GO (2000) Effect of three structurally related antimalarial drugs on liver microsomal components and lipid peroxidation in rats. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 126:217–224. https://doi.org/10.1016/S0742-8413(00)00116-X

    Article  CAS  Google Scholar 

  55. Pari L, Latha M (2005) Antihyperglycaemic effect of Scoparia dulcis.: effect on key metabolic enzymes of carbohydrate metabolism in streptozotocin-induced diabetes. Pharm Biol 42:570–576. https://doi.org/10.1080/13880200490901799

    Article  Google Scholar 

  56. Ogetii GN, Akech S, Jemutai J, Boga M, Kivaya E et al (2010) Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage. BMC Infect Dis 10:1–9. https://doi.org/10.1186/1471-2334-10-334

    Article  Google Scholar 

  57. David AB, Inuwa A, Malgwi SA, Mbaya AW, Abdulsalam H et al (2020) Effect of diminazene diaceturate (Sequzene) on serum biochemistry and associated histopathological changes of New-Zealand rabbits (Oryctolagus cuniculus) experimentally infected with Trypanosoma brucei brucei. J Parasitol Vector Biol 12:7–16. https://doi.org/10.5897/JPVB2020.0381

    Article  Google Scholar 

  58. Anosa V, Isoun T (1983) Pathology of experimental Trypanosoma vivax infection in sheep and goats. Zentralbl Veterinarmed B 30:685–700. https://doi.org/10.1111/j.1439-0450.1983.tb01894.x

    Article  CAS  PubMed  Google Scholar 

  59. Haanstra JR, van Tuijl A, van Dam J, van Winden W, Tielens AG et al (2012) Proliferating bloodstream-form Trypanosoma brucei use a negligible part of consumed glucose for anabolic processes. Int J Parasitol 42:667–673. https://doi.org/10.1016/j.ijpara.2012.04.009

    Article  CAS  PubMed  Google Scholar 

  60. Hannaert V, Bringaud F, Opperdoes FR, Michels PA (2003) Evolution of energy metabolism and its compartmentation in Kinetoplastida. Kinetoplastid Biol Dis 2:1–30. https://doi.org/10.1186/1475-9292-2-11

    Article  Google Scholar 

  61. van Hellemond JJ, Opperdoes FR, Tielens A (2005) The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei. Biochem Soc Trans 33:967–971. https://doi.org/10.1042/BST0330967

    Article  PubMed  Google Scholar 

  62. Mbaya AW, Aliyu MM, Nwosu CO, Ibrahim UI (2008) Captive wild animals as potential reservoirs of haemo and ectoparasitic infections of man and domestic animals in the arid-region of Northeastern Nigeria. Veterinarski arhiv 78:429–440. https://hrcak.srce.hr/28919

  63. Ezeh IO, Ugwu NE, Obi CF, Enemuo VO, Okpala MI et al (2019) Reduced fasting blood glucose levels following relapse in diminazene aceturate (Dinazene(®)) treated Trypanosoma brucei infected albino rats. J Parasit Dis 43:329–332. https://doi.org/10.1007/s12639-018-1074-z

    Article  PubMed  PubMed Central  Google Scholar 

  64. Marciacq Y, Seed JR (1970) Reduced levels of glycogen and glucose-6-phosphatase in livers of guinea pigs infected with Trypanosoma gambiense. J Infect Dis 121:653–655. https://doi.org/10.1093/infdis/121.6.653

    Article  CAS  PubMed  Google Scholar 

  65. Zhang K, Jiang N, Sang X, Feng Y, Chen R et al (2021) Trypanosoma brucei lipophosphoglycan induces the formation of neutrophil extracellular traps and reactive oxygen species burst via toll-like receptor 2, toll-like receptor 4, and c-Jun N-terminal kinase activation. Front Microbiol. https://doi.org/10.3389/fmicb.2021.713531

    Article  PubMed  PubMed Central  Google Scholar 

  66. Guilliams M, Bosschaerts T, Hérin M, Hünig T, Loi P et al (2008) Experimental expansion of the regulatory T cell population increases resistance to African trypanosomiasis. J Infect Dis 198:781–791. https://doi.org/10.1086/590439

    Article  CAS  PubMed  Google Scholar 

  67. Maurya R, Namdeo M (2021) Superoxide dismutase: a key enzyme for the survival of intracellular pathogens in host. React Oxygen Species. https://doi.org/10.5772/intechopen.100322

    Article  Google Scholar 

  68. Ali S, Rohilla A, Dahiya A, Kushnoor A, Rohilla S (2011) Streptozotocin induced diabetes: mechanisms of induction. Int J Pharm Res Dev 4:11–15

    Google Scholar 

  69. Azevedo-Martins AK, Lortz S, Lenzen S, Curi R, Eizirik DL et al (2003) Improvement of the mitochondrial antioxidant defense status prevents cytokine-induced nuclear factor-κB activation in insulin-producing cells. Diabetes 52:93–101. https://doi.org/10.2337/diabetes.52.1.93

    Article  CAS  PubMed  Google Scholar 

  70. Bhandari U, Chaudhari HS, Khanna G, Najmi AK (2013) Antidiabetic effects of Embelia ribes extract in high fat diet and low dose streptozotocin-induced type 2 diabetic rats. Front Life Sci 7:186–196. https://doi.org/10.1080/21553769.2014.881304

    Article  CAS  Google Scholar 

  71. Bollen M, Keppens S, Stalmans W (1998) Specific features of glycogen metabolism in the liver. Biochem J 336:19–31. https://doi.org/10.1042/bj3360019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cernea S, Dobreanu M (2013) Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochemia Medica 23:266–280. https://doi.org/10.11613/BM.2013.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bonaldo P, Sandri M (2013) Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech 6:25–39. https://doi.org/10.1242/dmm.010389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Al-Ziaydi AG, Al-Shammari AM, Hamzah MI, Jabir MS (2020) Hexokinase inhibition using d-mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells. Cancer Cell Int 20:1–10. https://doi.org/10.1186/s12935-020-01514-2

    Article  CAS  Google Scholar 

  75. Dhanesha N, Joharapurkar A, Shah G, Dhote V, Kshirsagar S et al (2012) Exendin-4 reduces glycemia by increasing liver glucokinase activity: an insulin independent effect. Pharmacol Rep 64:140–149. https://doi.org/10.1016/S1734-1140(12)70740-5

    Article  CAS  PubMed  Google Scholar 

  76. Rae C, McQuillan JA, Parekh SB, Bubb WA, Weiser S et al (2004) Brain gene expression, metabolism, and bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria. FASEB J 18:499–510. https://doi.org/10.1096/fj.03-0543com

    Article  CAS  PubMed  Google Scholar 

  77. Ramière C, Rodriguez J, Enache LS, Lotteau V, André P et al (2014) Activity of hexokinase is increased by its interaction with hepatitis C virus protein NS5A. J Virol 88:3246–3254. https://doi.org/10.1128/JVI.02862-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sen S, Kaminiski R, Deshmane S, Langford D, Khalili K et al (2015) Role of hexokinase-1 in the survival of HIV-1-infected macrophages. Cell Cycle 14:980–989. https://doi.org/10.1080/15384101.2015.1006971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Shah K, DeSilva S, Abbruscato T (2012) The role of glucose transporters in brain disease: diabetes and Alzheimer’s disease. Int J Mol Sci 13:12629–12655. https://doi.org/10.3390/ijms131012629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shi L, Salamon H, Eugenin EA, Pine R, Cooper A et al (2015) Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. Sci Rep 5:1–13. https://doi.org/10.1038/srep18176

    Article  CAS  Google Scholar 

  81. Yu L, Chen X, Wang L, Chen S (2018) Oncogenic virus-induced aerobic glycolysis and tumorigenesis. J Cancer 9:3699. https://doi.org/10.7150/jca.27279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kolwicz SC Jr, Tian R (2011) Glucose metabolism and cardiac hypertrophy. Cardiovasc Res 90:194–201. https://doi.org/10.1093/cvr/cvr071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206:2049–2057. https://doi.org/10.1242/jeb.00241

    Article  CAS  PubMed  Google Scholar 

  84. Pari L, Maheswari JU (1999) Hypoglycaemic effect of Musa sapientum L. in alloxan-induced diabetic rats. J Ethnopharmacol 68:321–325. https://doi.org/10.1016/S0378-8741(99)00088-4

    Article  CAS  PubMed  Google Scholar 

  85. Vats V, Yadav S, Grover J (2003) Effect of T. foenumgraecum on glycogen content of tissues and the key enzymes of carbohydrate metabolism. J Ethnopharmacol 85:237–242. https://doi.org/10.1016/S0378-8741(03)00022-9

    Article  CAS  PubMed  Google Scholar 

  86. Zarmouh MM, Subramaniyam K, Viswanathan S, Kumar P (2010) Cause and effect of Plumbago zeylanica root extract on blood glucose and hepatic enzymes in experimental diabetic rats. Afr J Microbiol Res 4:2674–2677. https://doi.org/10.5897/AJMR.9000142

    Article  Google Scholar 

  87. Allam L, Ogwu D, Agbede RI, Sackey AK (2011) Hematological and serum biochemical changes in gilts experimentally infected with Trypanosoma brucei. Veterinarski Arhiv 81:597–609. https://hrcak.srce.hr/72960

  88. Biryomumaisho S, Katunguka-Rwakishaya E, Rubaire-Akiiki C (2003) Serum biochemical changes in experimental Trypanosoma congolense and Trypanosoma brucei infection in Small East Africa goats. Veterinarski arhiv 73:167–180. https://hrcak.srce.hr/74864

  89. Hussain R, Khan A, Abbas RZ, Ghaffar A, Abbas G et al (2016) Clinico-hematological and biochemical studies on naturally infected camels with trypanosomiasis. Pak J Zool 48. https://primo.qatar-weill.cornell.edu/permalink/974WCMCIQ_INST/1e7q4lh/cdi_gale_infotracacademiconefile_A451949421

  90. Megahed GA, Abd Ellah MR, Abdel-Rady A (2012) Comparative biochemical studies on natural Trypanosoma evansi infection in she-camels. Comp Clin Pathol 21:1121–1124. https://doi.org/10.1007/s00580-011-1243-2

    Article  CAS  Google Scholar 

  91. Ekanem JT, Yusuf OK (2008) Some biochemical and haematological effects of black seed (Nigella sativa) oil on Trypanosoma brucei-infected rats. Afr J Biotechnol 7(2):153–157

    CAS  Google Scholar 

  92. Orhue NEJ, Nwanze EAC, Okafor A (2005) Serum total protein, albumin and globulin levels in Trypanosoma brucei-infected rabbits: effect of orally administered Scoparia dulcis. Afr J Biotechnol 4(10):1152–1155

    Google Scholar 

  93. Sow A, Sidibé I, Kalandi M, Bathily A, Ndiaye N et al (2014) Biochemical changes induced by natural infection of trypanosomosis in Burkinabese local donkey breeds. Comp Clin Pathol 23:103–109. https://doi.org/10.1007/s00580-012-1579-2

    Article  CAS  Google Scholar 

  94. Anosa V, Isoun T (1976) Serum proteins, blood and plasma volumes in experimental Trypanosoma vivax infections of sheep and goats. Trop Anim Health Prod 8:14–19. https://doi.org/10.1007/BF02383360

    Article  CAS  PubMed  Google Scholar 

  95. Singh D, Gaur S (1983) Clinical and blood cellular changes associated with Trypanosoma evansi infection in buffalo-calves. Indian J Anim Sci 53(5):498–502

    Google Scholar 

  96. Rajora V, Raina A, Sharma R, Singh B (1986) Serum protein changes in buffalo calves experimentally infected with Trypanosoma evansi. Indian J Vet Med 6:65–73

    Google Scholar 

  97. Daisy P, Saipriya K (2012) Biochemical analysis of Cassia fistula aqueous extract and phytochemically synthesized gold nanoparticles as hypoglycemic treatment for diabetes mellitus. Int J Nanomed 7:1189. https://doi.org/10.2147/IJN.S26650

    Article  CAS  Google Scholar 

  98. Rathod N, Raghuveer I, Chitme H, Chandra R (2009) Free radical scavenging activity of Calotropis gigantea on streptozotocin-induced diabetic rats. Indian J Pharm Sci 71:615. https://doi.org/10.4103/0250-474X.59542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Vanwalleghem G, Morias Y, Beschin A, Szymkowski DE, Pays E (2017) Trypanosoma brucei growth control by TNF in mammalian host is independent of the soluble form of the cytokine. Sci Rep 7:1–7. https://doi.org/10.1038/s41598-017-06496-2

    Article  CAS  Google Scholar 

  100. Li B, Wang Z, Fang J-J, Xu C-Y, Chen W-X (2007) Evaluation of prognostic markers in severe drug-induced liver disease. World J Gastroenterol WJG 13:628. https://doi.org/10.3748/wjg.v13.i4.628

    Article  CAS  PubMed  Google Scholar 

  101. Dkhil MA, Abdel-Gaber R, Khalil MF, Hafiz TA, Mubaraki MA et al (2020) Indigofera oblongifolia as a fight against hepatic injury caused by murine trypanosomiasis. Saudi J Biol Sci 27:1390–1395. https://doi.org/10.1016/j.sjbs.2019.11.038

    Article  CAS  PubMed  Google Scholar 

  102. Stijlemans B, Leng L, Brys L, Sparkes A, Vansintjan L et al (2014) MIF contributes to Trypanosoma brucei associated immunopathogenicity development. PLoS Pathog 10:e1004414. https://doi.org/10.1371/journal.ppat.1004414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Han K-H, Hashimoto N, Shimada K-i, Sekikawa M, Noda T et al (2006) Hepatoprotective effects of purple potato extract against d-galactosamine-induced liver injury in rats. Biosci Biotechnol Biochem 70:1432–1437. https://doi.org/10.1271/bbb.50670

    Article  CAS  PubMed  Google Scholar 

  104. Aquino LPCTd, Machado RZ, Alessi AC, Santana A, Castro MBd et al (2002) Hematological, biochemical and anatomopathological aspects of the experimental infection with Trypanosoma evansi in dogs. Arquivo Brasileiro de Medicina Veterinária e Zootecnia 54:8–18. https://doi.org/10.1590/S0102-09352002000100002

    Article  Google Scholar 

  105. Cadioli FA, Marques L, Machado R, Alessi A, Aquino L et al (2006) Experimental Trypanosoma evansi infection in donkeys: hematological, biochemical and histopathological changes. Arquivo Brasileiro de Medicina Veterinária e Zootecnia 58:749–756. https://doi.org/10.1590/S0102-09352006000500008

    Article  CAS  Google Scholar 

  106. Parashar R, Singla LD, Gupta M, Sharma SK (2018) Evaluation and correlation of oxidative stress and haemato-biochemical observations in horses with natural patent and latent trypanosomosis in Punjab state of India. Acta Parasitol 63:733–743. https://doi.org/10.1515/ap-2018-0087

    Article  CAS  PubMed  Google Scholar 

  107. Mbaya AW, Kumshe HA, Dilli HK (2014) Serum biochemical changes in dromedaries experimentally infected with Trypanosoma evansi and treated with melarsenoxyde cysteamine hydrochloride. Veterinarski arhiv 84:377–385. https://hrcak.srce.hr/125128

  108. Kalejaiye J, Ayanwale F, Ocholi R, Daniel A (1995) The prevalence of trypanosome in sheep and goats at slaughter. Israel J Vet Med 50:57–59

    Google Scholar 

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Acknowledgements

The authors appreciate Mr Joseph Egene of Physiology department, Bingham University Karu, for his technical suggestion and assistance in handling the animals and the trypanosome.

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  1. Department of Biochemistry, Faculty of Science and Technology, Bingham University, Karu, Nasarawa State, Nigeria

    Rotimi Johnson Ojo, Grace Manmak Paul, Dorcas Dedan Magellan, Dogwo Nahum Dangara & Gideon Gyebi

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  1. Rotimi Johnson Ojo
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  2. Grace Manmak Paul
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  3. Dorcas Dedan Magellan
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  5. Gideon Gyebi
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Contributions

RJO conceived and designed the study. GMP, DDM and DND performed the experiments. RJO supervised the experiments. RJO, GMP, DDM, DND and GG analysed the data. GMP, DDM and DND drafted the first manuscript. RJO edited and finalized the manuscript. GG drew the graphical abstract. All the authors read and approved the final manuscript.

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Correspondence to Rotimi Johnson Ojo.

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The international guidelines for animal research was used. Animals were humanely cared for in compliance with the principles of laboratory animal care in Bingham University Karu Nasarawa State, Nigeria.

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Ojo, R.J., Paul, G.M., Magellan, D.D. et al. Trypanosoma brucei brucei Induced Hypoglycaemia Depletes Hepatic Glycogen and Altered Hepatic Hexokinase and Glucokinase Activities in Infected Mice. Acta Parasit. 67, 1097–1106 (2022). https://doi.org/10.1007/s11686-022-00550-4

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