{"id":49875,"date":"2023-06-30T09:56:19","date_gmt":"2023-06-30T09:56:19","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=49875"},"modified":"2023-07-11T07:01:28","modified_gmt":"2023-07-11T07:01:28","slug":"effect-of-artesunate-on-haematological-and-plasma-biochemical-parameters-in-female-wistar-rats","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no2\/effect-of-artesunate-on-haematological-and-plasma-biochemical-parameters-in-female-wistar-rats\/","title":{"rendered":"Effect of Artesunate on Haematological and Plasma Biochemical Parameters in Female Wistar Rats"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Artesunate is a drug used to cure malaria 1<\/sup>. It belongs to the artemisinin class of drugs. It is frequently administered in the form of combination therapy, for example artesunate combine with mefloquine. It is not used as a prophylaxis.Artesunate can be administered through intravenous injection, muscular injection as well as through oral and rectal administrations 2<\/sup>. <\/p>\n\n\n\n

The drug is well tolerated when taken 3<\/sup>. It is preferred during the gestation period because of its high safety index, however contrary results were suggested by animal studies 4<\/sup>. It is also allowed to be taken by lactating mothers. Liu Xu invented this drug in 1977 5<\/sup> and the World Health Organization has listed it as an essential medicine 6<\/sup>. Although artesunate is used mainly to treat malaria, evidence abounds that it could also has advantageous effects on infection due Schistosoma haematobium<\/em> 7<\/sup>, but this has not been proven convincingly. <\/p>\n\n\n\n

Its efficacy is similar to that of arthemeter when used to treat adults\u2019 malaria induced by P. falciparum<\/em> 8<\/sup>, however artesunate in combination with other drugs has superior advantages relative to artemether-based drugs, vis-\u00e0-vis, through uptake and through the routes of administration and probably could be more efficacious when treating serious malaria in children9<\/sup>. Drugs that inactivate hepatic enzyme CYP2A6 should not be taking alongside with artesunate, examples of such drugs are amiodarone, letrozole isoniazid e.t.c. <\/p>\n\n\n\n

The effect of artesunate on: rats\u2019 kidneys toxicity 10<\/sup>, hemolysis and hypoglycemia induction in rats 11<\/sup>, developmental toxicities in rats and rabbits 12<\/sup>, hepatic histopathological changes in rats 13<\/sup>, embryotoxicity and toxicokinetics in rats 14<\/sup>, bone development toxicity in rats 15<\/sup>, reproductive function in female rats 16<\/sup>, stroke and other central nervous system therapeutic effects 17<\/sup> as well as on sub-chronic hemato-biochemical effects in rats 18<\/sup> have been reported.<\/p>\n\n\n\n

But, as a result of limited\ninformation obtained concerning the activities of artesunate on blood parameters in female\nrats, hence, this research intends to bridge this gap.<\/p>\n\n\n\n

Materials and Methods <\/strong><\/p>\n\n\n\n

Experimental\nAnimals<\/strong><\/p>\n\n\n\n

Ten\nfemale rodents of weight range 130 \u2013 150 g raised in the Animal Holding of\nABUAD were used in the current study. These rodents were accommodated in a\nconducive laboratory atmosphere with unlimited supply of feed and water; the\nacclimatization period was for two weeks. All animal experiments were carried\nout in accordance with ABUAD Ethical Committee\n(16\/MHS01\/015) on care and use of laboratory animals.<\/p>\n\n\n\n

Drug<\/strong><\/p>\n\n\n\n

Artesunate\n(Green Energy, China) was purchased from Danax Pharmacy, Ibadan, Nigeria. Among\nthese, artesunate (50 mg) was liquefied in 10 ml of distilled water to produce\na concentration of 5.0 mg\/ml. The dosage of the artesunate considered in this\nresearch was as recommended by the manufacturer.<\/p>\n\n\n\n

Dosage:\nAccording to the manufacturer, for adult 2 tablets (each tablet weighed 50 mg)\nwere to be given orally per day for a 70 kg adult.<\/p>\n\n\n\n

Hence,\n50 mg (x2) per day in a 70 kg adult.<\/p>\n\n\n\n

Therefore, dose to be used = 100\/70 mg\/kg<\/p>\n\n\n\n

=1.43 mg\/kg<\/p>\n\n\n\n

Experimental\nDesign<\/strong><\/p>\n\n\n\n

Ten\nmatured female rats (five per group) used for this study received the following\noral doses of artesunate and distilled water (control) for 50 days as follows: <\/p>\n\n\n\n

Group A rodents (control group) were given 0.5 ml\/100\ng of distilled water.<\/p>\n\n\n\n

Group B rodents were given 1.43 mg\/kg of artesunate..<\/p>\n\n\n\n

Blood\nsample collection<\/strong><\/p>\n\n\n\n

On day 51, blood\nsamples were collected from the rodents and prepared as previously described 19<\/sup>.<\/p>\n\n\n\n

Haematological\nParameters Determination <\/strong><\/p>\n\n\n\n

The red blood cells (RBC) count,\nwhite blood cells (WBC) count, hemoglobin (Hb) concentration, packed cell\nvolume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH)\nand mean corpuscular hemoglobin concentration (MCHC) were determined as\npreviously reported 19<\/sup>.<\/p>\n\n\n\n

Biochemical\nParameters Determination<\/strong><\/p>\n\n\n\n

The total protein concentration, albumin\nconcentration, globulin concentration, activities of plasma alanine\ntransaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase\n(ALP), levels of creatinine and urea (BUN) were determined as previously\nreported 20<\/sup>.<\/p>\n\n\n\n

Statistcal Analysis<\/strong><\/p>\n\n\n\n

Mean +\/- SEM and student\u2019s t-test at\np<0.05 were determined.<\/p>\n\n\n\n

Results<\/strong><\/p>\n\n\n\n

From\ntable 1, treatment of rodents with artesunate (1.43 mg\/kg) induced significant\n(p<0.05) reductions in RBC, platelet and lymphocyte values relative to their\ncontrols. However, the table also revealed that treatment of rodents with artesunate\n(1.43 mg\/kg) caused non-significant (p>0.05) changes in the other parameters\nas shown in the table.<\/p>\n\n\n\n

From\ntable 2, it was revealed that treatment of rodents with artesunate (1.43 mg\/kg)\ncaused significant (p<0.05) reductions in total protein, ALT and ALP values\nwhen compared to their controls. However, the table also revealed that treatment\nof rodents with artesunate (1.43 mg\/kg) produced non-significant (p>0.05)\nchanges in the other parameters as shown in the table.<\/p>\n\n\n\n

Table 1: Effect of treating rats with artesunate for 50 days on haematological parameters <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Parameters<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

Artesunate<\/strong><\/p>\n

(1.43  mg\/kg)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

PCV (%)<\/strong><\/p>\n<\/td>\n

\n

51.50  \u00b1 0.66<\/p>\n<\/td>\n

\n

49.00 \u00b1 0.15<\/p>\n<\/td>\n<\/tr>\n

\n

Hb (g\/dL)<\/strong><\/p>\n<\/td>\n

\n

16.75 \u00b1 0.34<\/p>\n<\/td>\n

\n

15.90 \u00b1 0.61<\/p>\n<\/td>\n<\/tr>\n

\n

RBC (\u00d7106<\/sup>\/\u00b5L)<\/strong><\/p>\n<\/td>\n

\n

8.66 \u00b1 0.04<\/p>\n<\/td>\n

\n

7.98 \u00b1 0.11*<\/p>\n<\/td>\n<\/tr>\n

\n

TWBC (\u00d7103<\/sup>\/\u00b5L)<\/strong><\/p>\n<\/td>\n

\n

10.76 \u00b1 0.36<\/p>\n<\/td>\n

\n

4.24 \u00b1 0.83<\/p>\n<\/td>\n<\/tr>\n

\n

Platelet (\u00d7105<\/sup>\/\u00b5L)<\/strong><\/p>\n<\/td>\n

\n

1.34 \u00b1 0.08<\/p>\n<\/td>\n

\n

0.68 \u00b1 0.07*<\/p>\n<\/td>\n<\/tr>\n

\n

Lymphocyte (%)<\/strong><\/p>\n<\/td>\n

\n

74.25 \u00b1 0.85<\/p>\n<\/td>\n

\n

71.75 \u00b1 0.83*<\/p>\n<\/td>\n<\/tr>\n

\n

Neutrophil (%)<\/strong><\/p>\n<\/td>\n

\n

23.50 \u00b1 0.89<\/p>\n<\/td>\n

\n

25.25 \u00b1 0.75<\/p>\n<\/td>\n<\/tr>\n

\n

Monocyte (%)<\/strong><\/p>\n<\/td>\n

\n

1.75 \u00b10.31<\/p>\n<\/td>\n

\n

1.50 \u00b1 0.28<\/p>\n<\/td>\n<\/tr>\n

\n

Eosinophil (%)<\/strong><\/p>\n<\/td>\n

\n

0.50 \u00b10.14<\/p>\n<\/td>\n

\n

1.50 \u00b1 0.36<\/p>\n<\/td>\n<\/tr>\n

\n

MCV (FL)<\/strong><\/p>\n<\/td>\n

\n

59.46 \u00b1 0.15<\/p>\n<\/td>\n

\n

61.33 \u00b1 0.12<\/p>\n<\/td>\n<\/tr>\n

\n

MCHC (g\/dL)<\/strong><\/p>\n<\/td>\n

\n

32.53 \u00b1 0.24<\/p>\n<\/td>\n

\n

32.47 \u00b1 0.21<\/p>\n<\/td>\n<\/tr>\n

\n

MCH (pg)<\/strong><\/p>\n<\/td>\n

\n

19.34 \u00b1 0.14<\/p>\n<\/td>\n

\n

19.91 \u00b1 0.20<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

(n=5, *p<0.05)<\/p>\n\n\n\n

Table 2:<\/strong> Effect of treating rats with artesunate for 50 days on plasma biochemical parameters <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Parameters<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

Artesunate<\/strong><\/p>\n

(1.43  mg\/kg)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Total Protein (g %)<\/strong><\/p>\n<\/td>\n

\n

8.70 \u00b1 0.07<\/p>\n<\/td>\n

\n

8.33 \u00b1 0.12*<\/p>\n<\/td>\n<\/tr>\n

\n

Albumin (gm %)<\/strong><\/p>\n<\/td>\n

\n

3.40 \u00b1 0.08<\/p>\n<\/td>\n

\n

3.40 \u00b1 0.14<\/p>\n<\/td>\n<\/tr>\n

\n

Globulin (gm %)<\/strong><\/p>\n<\/td>\n

\n

5.30 \u00b10.04<\/p>\n<\/td>\n

\n

4.93 \u00b1 0.12<\/p>\n<\/td>\n<\/tr>\n

\n

AST (\u00b5\/L)<\/strong><\/p>\n<\/td>\n

\n

45.00 \u00b1 0.92<\/p>\n<\/td>\n

\n

42.25 \u00b1 1.03<\/p>\n<\/td>\n<\/tr>\n

\n

ALT (\u00b5\/L)<\/strong><\/p>\n<\/td>\n

\n

33.25 \u00b1 0.63<\/p>\n<\/td>\n

\n

31.50 \u00b1 0.74*<\/p>\n<\/td>\n<\/tr>\n

\n

ALP (IU\/L)<\/strong><\/p>\n<\/td>\n

\n

113.00 \u00b1 1.93<\/p>\n<\/td>\n

\n

110.50 \u00b1 2.23*<\/p>\n<\/td>\n<\/tr>\n

\n

BUN (mg\/dL)<\/strong><\/p>\n<\/td>\n

\n

17.53 \u00b1 0.17<\/p>\n<\/td>\n

\n

17.30 \u00b1 0.13<\/p>\n<\/td>\n<\/tr>\n

\n

Creatinine (\u00b5mol\/L)<\/strong><\/p>\n<\/td>\n

\n

0.78 \u00b1 0.02<\/p>\n<\/td>\n

\n

0.73 \u00b1 0.03<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

(n=5,\n*p<0.05)<\/p>\n\n\n\n

Discussion <\/strong><\/p>\n\n\n\n

The\nresults have revealed that artesunate induced significant reduction in RBC\nvalue which suggests that the drug prevented erythropoietin secretion by the\nkidneys and caused decrease in oxygen binding capacity of blood with ultimate\nreduction in the quantity of oxygen transported to the tissues. Similar account\nwas given by 21<\/sup> in rodents treated with extract of Plectranthus amboinicus<\/em>. This result was\ncorroborated by the assertions of 22, 23<\/sup>.<\/p>\n\n\n\n

Also,\nartesunate induced significant decrease in the platelet count which suggests\nthat it prevented the haemostatic function of the body. Opposite result was\ngiven by 24<\/sup> in rats treated with extract of Fadogia agrestis<\/em>.<\/p>\n\n\n\n

The\ndrug caused insignificant change in TWBC value which suggests that it had no\neffect on resistance of the body to foreign pathogens. Opposite result was\ngiven by 25<\/sup> in rodents treated with extract of Viscum album<\/em>. This result was supported by the assertions of 26<\/sup>.<\/p>\n\n\n\n

Artesunate\nproduced significant decrease in lymphocyte count which could signify the body\nacquired immune suppression. Opposite result was given by 27<\/sup> in rodents\ntreated with isolated ergosterol.<\/p>\n\n\n\n

Further,\nthe drug produced non-significant change in eosinophil value which suggests the\nabsence of anti-allergic and anti-parasitic infectious responses by the drug.\nOpposite result was given by 28<\/sup> in rats and mice treated with\nextract of Arctotis actotoides<\/em>.<\/p>\n\n\n\n

Artesunate\ncaused non-significant change in the neutrophil value which suggests the drug\nhad no effect on the body response to pathogenic bacteria, viruses and other\nharmful agents. Opposite result was given by 29 <\/sup>in rodents treated\nwith extract of Dennettia tripetala<\/em>. <\/p>\n\n\n\n

The\ndrug induced non-significant change in the monocyte value which suggests that\nit lacked phagocytic function 30<\/sup>. Opposite result was given by 31<\/sup>\nin hens fed with Saccharomyces cerevisiae<\/em>.<\/p>\n\n\n\n

Artesunate\nproduced non-significant changes in MCV and MCH values which suggests the\nabsence of effect on macrocytic anaemia induction. Similar account was given by\n32<\/sup> inrats treated with extract of Jatropha gossypifolia. <\/em><\/p>\n\n\n\n

The\ndrug produced insignificant change in the MCHC value which suggests absence of\neffect on hereditary spherocytosis induction. Similar account was given by 32<\/sup>\nin rats treated with extract of Jatropha\ngossypifolia<\/em>.<\/p>\n\n\n\n

It has been reported that\n<\/sup>treatment of rats for 45 days with\nartesunate (2 mg\/kg and 4 mg\/kg) caused non-significant changes in hemoglobin, RBC,\nMCH, MCHC, lymphocytes and platelet values; but, the study also revealed that\nat 8.0 mg\/kg, it caused significant (p< 0.01) increase in PCV, MCH, TWBC,\nneutrophil and eosinophil values 18<\/sup>.<\/p>\n\n\n\n

The\nplasma biochemical study results have revealed that artesunate caused significant\nreduction in total protein level which suggests that the drug inhibited blood buffering\ncapacity and also decrease the colloidal osmotic pressure. Opposite result was\ngiven by 33<\/sup> in rodents treated with extract of Euphorbia heterophylla<\/em>. This result was validated by the assertion\nof 26<\/sup><\/p>\n\n\n\n

In\naddition, artesunate produced significant reduction in ALT activity which could\nmean that it prevented the induction liver damage. Opposite result was given by\n34<\/sup> in rodents treated with extract of Moringa oleifera<\/em>.<\/p>\n\n\n\n

Artesunate\ncaused significant decrease in ALP activity which suggests the inhibition of\ncholestasis. Opposite result was given by 35<\/sup> in rats treated with\nlosartan. This result was corroborated by the assertion of 36<\/sup>.<\/p>\n\n\n\n

Artesunate\ninduced non-significant change in the level of albumin which suggests that it\nhad no effect on the levels of essential plasma components like amino acids,\nmetals, bilirubin e.t.c. Contrary result was given by 37<\/sup> in rats\ntreated with extract of Enicostemma\naxillare<\/em>.<\/p>\n\n\n\n

Artesunate\ncaused non-significant change in globulin level which suggests the lack of\neffect on both the natural and acquired immunity of the body. Similar account\nwas given by 38<\/sup> in rats treated with extracts of Portulaca oleracea<\/em>.<\/p>\n\n\n\n

The\ndrug caused insignificant change in AST activity which could mean the lack of\neffect on induction of tissue necrosis. Opposite result was given by 39<\/sup>\nin rodents treated with extract of Sida\nrhombifolia<\/em>.<\/p>\n\n\n\n

Artesunate\ncaused non-significant change in BUN level which suggests the absence of\nnephrotoxicism. Opposite result was given by 40<\/sup> in rats treated with\nextract of Passiflora edulis<\/em>. This\nresult was corroborated by the assertion of 41<\/sup>.<\/p>\n\n\n\n

Artesunate\nproduced non-significant change in creatinine level which suggests the absence\nof renal dysfunction. Opposite result was given by 42<\/sup> Mucuna pruriens<\/em> extract treated rats.<\/p>\n\n\n\n

It has also been reported that\n<\/sup>treatment of rats for 45 days with\nartesunate (4 mg\/kg and 8 mg\/kg) caused significant (p< 0.05\u20130.001) increase\nin SGOT, SGPT, ALP, TC, TG values; at 8.0 mg\/kg, it also caused significant (p<\n0.05) increase in bilirubin level. However, at 2.0 mg\/kg, 4.0 mg\/kg and 8.0\nmg\/kg, it caused non-significant changes in total protein, albumin, creatinine\nand urea levels 18<\/sup>.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Conclusively,\nit can be suggested that artesunate had both harmful and advantageous effects\non blood parameters in female Wistar rats.<\/p>\n\n\n\n

Limitations of the Study<\/strong><\/p>\n\n\n\n

Scantiness of prior research studies on the topic: There were limited information obtained from literature concerning the activities of artesunate on blood parameters in female rats prior to the commencement of this study.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

The authors would like to acknowledge the Management of Afe Babalola University, Ado-Ekiti for supporting this work. <\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

There is absence of conflicting interests in this study.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

  1. World Health Organization. Artesunate. March 2013. Archived from the original (PDF) on 28   December 2013. Retrieved 7 December 2016.<\/li>
  2. World Health Organization. Rectal artesunate for pre-referral treatment of severe malaria. Global Malaria Programme (Report). World Health Organization, 2018.<\/li>
  3. Rosenthal P.J. Artesunate for the treatment of severe falciparum malaria. The New England J. Med., 2008; 358 (17): 1829\u20131836.<\/li>
  4. Kovacs S.D, Rijken M.J and Stergachis A. Treating severe malaria in pregnancy: a review of the evidence. Drug Safet<\/em>., 2015; 38 (2): 165\u2013181.<\/li>
  5. Li G., Li Y., Li Z. and Zeng M. Artemisinin-based and other antimalarials: detailed account of studies by Chinese scientists who discovered and developed them. Academic Press, 2017; ISBN 9780128132111.<\/li>
  6. World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization, 2019.<\/li>
  7. Boulanger D., Dieng Y., Cisse B., Remoue F., Capuano F., Dieme J.L,et al. Antischistosomal efficacy of artesunate combination therapies administered as curative treatments for malaria attacks. Transact. Royal Societ. Tropic. Med. Hyg., 2007; 101 (2): 113\u2013116.<\/li>
  8. Phu N.H, Tuan P.Q, Day N., Mai N.T, Chau T.T, Chuong L.V, et al. Randomized controlled trial of artesunate or artemether in Vietnamese adults with severe falciparum malaria. Malaria J., 2010; 9 (1): 97.<\/li>
  9. Li Q. and Weina P. Artesunate: The best drug in the treatment of severe and complicated malaria. Pharmaceuticals<\/em>., 2010; 3 (7): 2322\u20132332.<\/li>
  10. Danladi S.A, Mumuni M., Joseph V.Z, Aminu A.R, Nuhu S., Lucy A. and Tarfa M. Effect of oral administration of artesunate on the histology of the kidney in albino rat. IOSR J. Dent. Med. Sci.<\/em>, 2013; 3 (5): 15-20.<\/li>
  11. Salman M.T, Peter O., Abdullateef I.A and  Lawrence A.O.  <\/sup>Artesunate-induced hemolysis and hypoglycemia in rats: Gender implication and role of antioxidant enzymes. J. Appl. Hem<\/em>., 2017; 8 (1): 23-32. <\/li>
  12. Clark R.L, Tacey E.K.W, Sally A.C, Ian G., Peter W. and Stephen A.W. Developmental toxicity of artesunate and an artesunate combination in the rat and rabbit. Birth Defects Res. B. Dev. Reprod. Toxicol<\/em>., 2004; 71 (6): 380-394.<\/li>
  13. Mohamed S.A, Muheet A.S, Mukhtar A. and Sarah M. Histopathological changes induced by artesunate in liver of Wistar rat. Inter. J. Pharmacol<\/em>., 2017; 13: 104-108. <\/li>
  14. Moon-Koo C., Wook-Joon Y., Jin-Soo L. and Jong-Hwa L. Embryotoxicity and toxicokinetics of the antimalarial artesunate in rats.<\/strong> Toxicol. Res<\/em>., 2013; 29 (1): 27 – 34. <\/li>
  15. Adebisi S. Assessment of the effect of artesunate on the developing bones of wistar rat animal model of malaria treatment. AF Prev. Med. Bull<\/em>., 2010; 9 (1): 23 – 28.<\/li>
  16. Oyedeji K.O. Effect of artesunate on reproductive function in female Wistar rats. Int. J. Pharm. Sci. Rev. Res<\/em>., 2021; 71 (2): 72-75.<\/li>
  17. Shilun Z.,Qiang L., Xin L.,Hua F. and Yujie C.The potential therapeutic effect of artesunate on stroke and other central nervous system diseases. Biomed. Res. Inter<\/em>., 2016; |Article ID 1489050.<\/li>
  18. Bigoniya P., Sahu T. and Tiwari V. Hematological and biochemical effects of sub-chronic artesunate exposure in rats. Toxicol Rep<\/em>., 2015; 2: 280-288.<\/li>
  19. Oyedeji K.O., Adurodija M.N., Adeleye A.S. and Abidoye D. Effect of ethanol extract of Adenopus breviflorus<\/em> on haematological and plasma biochemical parameters in male albino rats. Int. J. Pharm.Sci.Rev. Res<\/em>., 2015; 35: 36-40.  .  <\/li>
  20. Oyedeji K.O., Okeke O.E., Adeleke K.O. and Oni J. Effect of atenolol (Beta blocker) on haematological and plasma biochemical parameters in male Wistar rats. Int. J. Pharm. Sci. Rev. Res<\/em>., 2019; 54 (2): 1-5.<\/li>
  21. Melva S. and Pasar M.S. Haematological profile of rats (Rattus norvegicus) induced BCG and provided leaf extract of Plectranthus amboinicus<\/em>. The 4th Inter. Conf. on Res., Implement., and Edu. Maths. Sci.; 2017.<\/li>
  22. Polenakovic M. and Sikole A. Is erythropoietin a survival factor for red blood cells? J. Am. Soc. Nephrol<\/em>., 1996; 7 (8): 1178 – 1182.<\/li>
  23. 23. American Diabetes Association. Nutrition recommendation and principles for people with diabetes mellitus clinical practice recommendations. Diabet Care<\/em>., 2000; 23:543-546. <\/li>
  24. Yakubu M.T, Akanji M.A and Oladiji A.T. Hematological evaluation in male albino rats following chronic administration of aqueous extract of Fadogia agrestis<\/em> stem. Pharmacog. Mag<\/em>., 2007; 3: 34 – 38.<\/li>
  25. Imoru J.O, Eno A.E, Unoh F.B, Enkanu E., Ofem O.E and Ibu J.O. Haematopoietic agents in the crude extracts from the leaves of Viscum album <\/em>(mistletoe). Nigerian J. Health Biomed. Sci<\/em>., 2005; 4 (2): 139-145.<\/li>
  26. Ganong W.F. Review of Medical Physiology(22nd<\/sup>). New York, Lange Medical books\/Mc Graw Hill; 2005.<\/li>
  27. Oyedeji K.O, Bolarinwa A.F and Oladosu I.A. Effect of isolated ergosterol constituent of  Portulaca oleracea<\/em> on Haematological Parameters in male albino rats. Asian J. Pharm. Clinic Res<\/em>., 2013; 6: 2.<\/li>
  28. Jimoh F.O, Adedapo A.A, Sofidiya M.O, Masika P.J and Afolayan A.J. Safety evaluation of the extract from the shoots of Arctotis actotoides <\/em>in rats and mice. Afri. J. Biotech<\/em>., 2008; 7 (18): 3173-3177. <\/li>
  29. Ikpi D.E and Nku C.O. Effect of ethanolic extract of Dennettia tripetala <\/em>fruit on haematological parameters in albino Wistar rats. Nigerian J. Physiol. Sci<\/em>., 2008; 23(1-2): 13-17.<\/li>
  30. Guyton A.C and Hall J.E. Textbook of Medical Physiology, 11th edition, Elsevier Inc; 2006.<\/li>
  31. Matur E., Erqul E., Erasian E., Inal G., Bilgic S. and Demircan H. Effect of Saccharomyces cerevisiae<\/em> extract on haematological parameters, immune functions and the antioxidant defense system in breeder hens fed aflatoxin contaminated diets. British Poultr. Sci<\/em>., 2011; 52 (5): 541-550.<\/li>
  32. Oyedeji K.O, Awoyinka D. and Abidoye D. Effect of ethanol extract of Jatropha gossypifolia<\/em> on haematological and plasma biochemical parameters in male albino rats. Int. J. Pharm. Sci. Rev. Res<\/em>., 2015; 35 (2): 41-45.<\/li>
  33. Apiamu A. and Evuen U.F. Biochemical assessment of the effect of aqueous leaf extract of Euphorbia Heterophylla Linn<\/em> in hepatocytes of rats. IOSR J. Environ. Sci, Toxicol. Food Tech<\/em>., 2013; 3 (5): 37- 41.<\/li>
  34. Ajibade T.O, Olayemi F.O and Arowolo R.O.A. The haematological and biochemical effects of methanol extract of the seeds of Moringa oleifera<\/em> in rats. J. Med. Plant Res<\/em>., 2012; 6 (4): 615-621.<\/li>
  35. Oyedeji K.O, Okeke O.E, Talabi Y.J and Oyawale G. Effect of losartan (Angiotensin II antagonist)on haematological and biochemical parameters in male Wistar rats. J. Pharm. Sci. Res<\/em>., 2018; 10 (5): 995-998.<\/li>
  36. Vasudevan D.M and Sreekumari S. Textbook for biochemistry for medical students. Jaypee          <\/li>
  37. Brothers Medical Publishers Ltd, New Delhi, 5th<\/sup> ed, 266; 2007.<\/li>
  38. Gite V.N, Pokharkar R.D, Chopade V.V and Takate S.B. Hepato-Protective activity of Enicostemma Axillare <\/em>in paracetemol induced hepato-toxicity in albino rats. Inter. J. Pharm. Life Sci.<\/em>, 2010; 1 (2): 50 \u2013 53.<\/li>
  39. Oyedeji K.O and Bolarinwa A.F. Effects of crude Extracts of Portulaca oleracea<\/em> on haematological parameters in albino rats. Afri. J. Biomed. Res<\/em>., 2010; 15: 41- 47.<\/li>
  40. Ouedraogo M., Zerbo P., Konate K., Barro N., Laya L. and Sawadogo. Effect of long-term use of Sida rhombifolia L.<\/em> extract on ha,ematological parameters of experimental animals. British J. Pharmacol. Toxicol.<\/em>, 2013; 4 (1): 18-24.<\/li>
  41. Devaki K., Beulah U., Akila G. and Gopalakrishnan V.K. Effect of aqueous extract of Passiflora edulis <\/em>on biochemical and haematological parameters of wistar albino rats. Toxicol. Inter<\/em>., 2012; 19 (1): 63-67. <\/li>
  42. Oduola T., Adeosun G.O, Oduola T.A, Avwioro G.O. and Oyeniyi M.A. Mechanism of action of Jatropha gossypifolia<\/em> stem latex as a haemostatic agent. Euro. J. Gen. Med<\/em>.,2005; 2 (4): 140\u2013143.<\/li>
  43. Adepoju O.O and Odubena J.A. Effect of Mucuna pruiens<\/em> on some hematological and biochemical parameters. J. Med. Plants Res<\/em>., 2009; (3): 73-76.<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction Artesunate is a drug used to cure malaria 1. It belongs to […]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[107],"tags":[],"class_list":["post-49875","post","type-post","status-publish","format-standard","hentry","category-vol16no2"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/49875","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=49875"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/49875\/revisions"}],"predecessor-version":[{"id":50297,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/49875\/revisions\/50297"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=49875"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=49875"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=49875"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}