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International Journal of Toxicology and Environmental Health

Vol. 4(1), pp. 045-053, July, 2019. © www.premierpublishers.org, ISSN: 1822-424X

Research Article

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts


of Annona Muricata Leaves and Fagara Zanthoxyloide Roots
on Zidovudine-Induced Wistar Rats
*Ekere, O.U.1, Ogunka-Nnoka, C.U. 2, Monago-Ighorodje, C.C.3
1,2,3Department of Biochemistry, University of Port Harcourt, Choba, Port Harcourt, River State, Nigeria.

The study determined the effects of administration of ethanol extracts of Annona muricata leaves
(AML) and Fagara zanthoxyloide roots (FZR) on liver and kidney indices in zidovudine (ZDV)-
induced Wistar rats. Animals were grouped into five (5); group 1 served as normal control, groups
2-5 were induced with 100g/mlZDV/Kgbw and group 3 treated with 35IU/Kgbw of erythropoietin,
group 4 with 4.5g/mlAML/Kgbw and group 5 with 3.8g/mlFZR/Kgbw for six weeks. Serum liver
enzymes, other biochemicals (total protein, albumin, globulin, bilirubin, urea and creatinine),
organ weights and histological examination were used to assess the impact on the liver and
kidney using standard methods. A significant elevation (p≤0.05) in the activities of serum liver
enzymes and bilirubin accompanied by a significant decrease (p≤0.05) in the other biochemicals
were observed in group 2. Treatment with extracts resulted in a modulation of the induced effects
of ZDV causing a significant decrease in the serum liver enzymes, bilirubin and increase in the
total protein, albumin and globulin concentrations. Histology of the liver showed altered
architecture, blood vessel congestion and necrosis; while the kidneys were hypoplastic with
signs of swelling (group 2) which was gradually reverted on treatment with extracts. The study
suggests that extracts of AML and FZR may confer some degree of protection to the liver and
kidney.

Keywords: Annona muricata, Fagara zanthoxyloide, zidovudine, hepatotoxicity, nephrotoxicity, Wistar rat

INTRODUCTION

Plants are fast becoming an important source of life-saving (kidney) an impairment in their function would adversely
medications for individuals with several symptoms or affect their health status (Belonwu et al., 2013). The
ailments.The preference and increasing interest given to degree of impairment may be measured by the activities of
traditional system of medicine over synthetic/orthodox several liver enzymes in serum dislodged as a result of
medication has spurred research into the toxicological damage to the liver or by a measure of the concentration
impact of these plants with regards to hepatotoxicity and of certain biochemical compounds (bilirubin, creatinine,
nephrotoxicity as these organs serve as initial contact urea) in the blood produced by or expected to be bio-
points for chemicals and toxins as they enter and as they transformed by the liver and excreted by the kidney (Adisa
are excreted from the body. The liver as a vital organ, is et al., 2014).
involved in the metabolism of drugs and exogenous
compounds, breakdown of nutrients, the buildup of body
tissues, storage sites for vitamins and minerals and
elimination of toxins (Adisa et al., 2014). The kidneys are
involved in the removal of waste products, re-absorption of *Corresponding Author: Ekere Oghenekaro
nutrients and maintaining electrolyte concentrations in the Uchechukwu, Department of Biochemistry, University of
body etc. As these two organs are of great importance for Port Harcourt, Choba, Port Harcourt, River State, Nigeria.
biotransformation (liver) and the subsequent excretion Email: Oghenekarouche@gmail.com

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts of Annona Muricata Leaves and Fagara Zanthoxyloide Roots on Zidovudine-Induced Wistar Rats
Ekere et al. 046

Annona muricata (AM) commonly called soursop in MATERIALS AND METHOD


Nigeria is widely distributed in the tropical regions of West-
Africa. The leaves, barks, fruits and seeds have been Collection of plant materials
recorded to possess several medicinal applications
(Badrie and Schauss, 2009). The leaves have been Annona muricata leaves (AML) and Fagara zanthoxyloide
applied or ingested as decoctions in cases of mild pains roots (FZR) were obtained from Alakahia, Obio/Akpor
and also used in the treatment of symptoms associated L.G.A, Rivers State, Nigeria. The plant materials were
with cold and asthma (Coria-Tellez et al., 2018). The barks identified by Dr. B. Chikezie of the Plant Science and
and seeds have been used in the treatment of Biotechnology Department, University of Port-Harcourt.
hypertension, diabetes, bacterial infections, inflammatory
diseases and cancer (Ezurike and Prieto, 2014; De souza Preparation of plant materials
et al., 2011). They are reported to be rich in alkaloids,
phenols, essential oils, acetogenins, carbohydrates, fiber The AML and FZR collected were sterilized with a stream
and other compounds (Ekere et al., 2019). of distilled water and left to air dry at 25˚C. They were
pulverized with a mechanical grinder until a uniform coarse
Fagara zanthoxyloide (FZ) is a plant common to the rain powder is obtained for each.
forests of Southern Nigeria. The leaves have been
reported to contain alkaloids, steroids, lignans and Extraction of plant materials
carbohydrates (Ekere et al., 2019). The most common
traditional application is in the treatment of toothaches, The dried powdered materials (300g) were placed in a
urinary and venereal disease. It has also been used as conical flask and extracted using 3 litres of absolute
components of antiseptics, anti-parasitic, anti- ethanol for 1 week. The mixture was centrifuged and
hypertensive, anti-inflammatory and analgesics filtered. The residue was evaporated to dryness and stored
(Adefisoye et al., 2012; Ogwal-Okeng et al., 2003). The at 4°C in a refrigerator.
most important discovery on the roots of Fagara
zanthoxyloide is their proposed use as an anti-sickling Animal Experimental treatments
agent due to the activity of 2-hydroxylmethy benzoic acid
(a bio-component of the root extract) on the red cell Seventy (70) albino rats weighing (200-250g) were
membrane and preservation of the colour of the blood. purchased from the animal house of the Department of
Biochemistry, University of Port Harcourt, Rivers State,
Zidovudine is a nucleoside reverse transcriptase inhibitor Nigeria and divided into five groups of 15 rats each; and
initially applied in the treatment of cancer and currently housed in Griffin and George modular cage system
being used as part of highly active antiretroviral therapy
(Ekere and Ikpeama, 2019; Peters et al., 2014). It has Group 1: Served as the normal control group which
been linked with several side effects such as anaemia, loss received only water and normal feed
of appetite, weight loss, leucopenia, oxidative stress, Group 2: Served as the negative control group which
thrompocytopenia, nausea, vomiting and shortness of received 100mg/ml of ZDV/Kg bw
breath etc. The culmination of these effects and the Group 3: Served as the positive control which received
important role this drug plays in the maintenance of health 35IU EPO/Kg bw
in conditions of immunodeficiency has spurred research Group 4: Received 100mg/ml ZDV/Kg bw and
into tackling the side effects of this drug. 4.5g/mlAML/Kg bw
Group 5: Received 100mg/ml ZDV/Kg bw and
The saying that health is wealth is one that has been said 3.8g/mlFZR/Kg bw
one too many in Nigeria. The management of the health
status in rural areas in Nigeria is plagued by the METHODS
occurrence of several side effects which according to
medical practitioners interviewed ranged from appetite Zidovudine (ZDV) was administered for two weeks in
loss, weight loss, immune suppression, anaemia etc. In groups 2-5, prior to experimental treatment with extracts
lieu to curb mitigating side effect, several rural dwellers while treatment with extracts was performed for a period of
indulge in the consumption of several tradio-medical 6 weeks. Twenty-four (24) hours after termination of
concoctions. Several plants are acclaimed to be wonder- experimentation, the animals were weighed and
working by traditional medicine dispensers in South- anaesthetized in chloroform. Blood samples were
southern Nigeria and include Annona muricata and Fagara collected into heparinized bottles from the jugular vein and
zanthoxyloide. This study aims at evaluating and providing centrifuged at 500 rpm for 12 minutes to obtain the serum.
insights into the long-term toxicological impacts of the The liver and kidney were also excised after dissection;
extracts of these plants on the liver and kidney in cases of with the variations in body and organ weights determined
possible side effects induced by zidovudine in Wistar rats by the method described by Akinnawo et al., (2005).
(Ekere and Ikpema, 2019; Ekere et al., 2019, Peters et al.,
2014).

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts of Annona Muricata Leaves and Fagara Zanthoxyloide Roots on Zidovudine-Induced Wistar Rats
Int. J. Toxicol. Environ. Health 047

Analysis of liver and kidney indices


The results of the body weight in group 2 may culminate
Assay for the activities of aspartate aminotransferase the findings that the drug induces loss of appetite and may
(AST), alanine aminotransferase (ALT) and alkaline elicit certain factors which results in a subtle derangement
phosphatase (ALP) in serum were performed by the of the neurochemical signaling with regards to appetite
method described by Reitman and Frankel (1957) using stimulation in the brain (Satya et al., 1999). The resultant
Randox test kits. Serum urea concentrations was effect would be a termination of neuromodulators related
measured enzymatically with urease and glutamine to appetite thus reducing food intake and concomitantly
dehydrogenase, creatinine levels were determined by the body weight loss. The results of group 4 and 5 may
kinetic calorimetric method with alkaline picrate and suggest that extract co-administration possibly through the
bilirubin concentration was performed by the methods presence of some bioactive compounds (Ekere et al.,
described by Yakubu et al., (2007). Total protein, albumin 2019), may have cushioned or reversed the
and globulin were assayed according to the method neurochemical derangement thereby regulating food
described by George, (2009). intake and thus body weight (Figure1).

Histological examination The weights of the liver and kidney were also observed to
decrease in group 2 when compared to the normal control
The excised organs were histologically examined by the (group 1), while treatment with extracts of AML and FZR
method described by Al-Hasawi and Al-Harbi (2014). resulted in an increase in the liver and kidney weights.

STATISTICAL ANALYSIS

Values obtained were expressed as Mean ± Standard


error of mean with analysis performed using SPSS
software version 20 for Windows (SPSS Inc. USA) at
p≤0.05 significant level.

RESULTS

Body and organ weight


Figure 2: Liver weights in zidovudine induced rats treated
The results of the variations in body and organ weights as with extract of Annona muricata leaves and Fagara
presented in Figures 1-3, showed a decrease in the body zanthoxyloide roots"
weight of group 2 when compared to the normal control
(group 1) but significant increases (p≤0.05) in the body
weight in groups administered when compared to the
negative control group. Treatment with extracts of AML
resulted in an increase in the body weight within the group
as time progress with the values observed to be
significantly higher (p≤0.05) than the negative control
group but lower in the normal control. The body weights on
treatment with FZR were significantly higher (p≤0.05) also
followed a similar trend in comparison with the AML and
FZR treatment but the weights were significantly higher
(p≤0.05) with FZR than AML. Figure 3: Kidney weights in zidovudine induced rats
treated with extract of Annona muricata leaves and Fagara
zanthoxyloide roots.

Organ weight, judged as a sensitive indicator of toxicity


even in the absence of any morphological changes
(Mandal et al., 2012) was observed to reduce in the
negative control group when compared to the normal
control; possibly due to the reduction in body weights
observed during the study (Nirogi et al., 2013). The
reductions observed at weeks 4 and 6 may be linked to an
underlying pathological condition such as necrosis and
Figure 1: Body weights in zidovudine induced rats treated degenerative disorders (Miyauchi et al., 2013).The
with extract of Annona muricata leaves and Fagara increases in organ weight observed in treatment groups
zanthoxyloide roots. may signify proper metabolism or histological disorder

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts of Annona Muricata Leaves and Fagara Zanthoxyloide Roots on Zidovudine-Induced Wistar Rats
Ekere et al. 048

(abnormal mass, contusions or tumours) which can be


ruled out on histological examination (Miyauchi et al., The significant increase (p≤0.05) in the activities of liver
2013). enzymes in group 2 (Figure 4-6) may suggest
hepatotoxicity which progressed to weeks 6 (Belonwu et
Liver and kidney indices al., 2013). Some researchers (Ogunka-Nnoka et al., 2019,
Obi et al., 2014 and Imafidon and Okunrobo 2012) have
Results of the activities of liver enzymesare shown in reported that elevated levels of ALT, AST and ALP in
Figure 4-6. There was significant increase in the AST, ALT serum are associated with acute liver toxicity. Adebayo et
and ALP activities after administration of 100mg ZDV/Kg al., (2010) also reported that a deranged increase in ALP
bw (Group 2) when compared to the normal control (Group activity as observed in this study may be an indication of
1). The positive control (Group 3) also showed an increase bone marrow disorder induced as a result of ZDV
in the serum activities of the liver function enzymes administration. Hence the changes in AST, ALT and ALP
investigated when compared to the normal control may suggest that ZDV induces hepatic damage and/or
(Group1) but asignificant reduction (p≤0.05) when disorders which relate to/or are associated with
compared with the negative control (group 2). Extracts of osteotoxicity or myelotoxicity. The significant reductions in
AML and FZR (Groups 4 and 5) resulted in significant the activities of liver enzymes on administration with
reductions (p≤0.05) in the activities of the liver function extracts as seen in groups 4-5 when compared with group
enzymes at week 2 when compared with the negative 2 may also suggest the ability of these plants to confer
control (group 2). Prolonged simultaneous administration protection to the liver against ZDV induced toxicity;
(weeks 4 and 6) resulted in a reduction in the serum confirming the beneficial effects of these plants in alcoholic
activities of AST and ALT but an increase in the ALP hepatitis conditions as proposed by folkloric medicine
activity when compared with both negative and positive dispensers (Adebayo et al., 2010). The decreases in the
control groups. ALP activity may also suggest its use in conditions which
results from bone marrow related toxicity.
160 week 2 week 4 week 6
140 The result of the administration of ZDV (group 2) on
120 selected liver biochemical indices shown in Figure 7-10
AST (IU/L)

100 revealed significant reductions (p≤0.05) in the


80 concentrations of total protein, albumin and globulin when
60 compared with the group 1. The treatment with AML and
40 FZR resulted in a significant increase in the concentration
20 of these liver biochemical indices when compared to the
0 negative control (Group 2) while the values observed in the
Group 1 Group 2 Group 3 Group 4 Group 5
positive control (group 3) were observed to be significantly
160 week 2 week 4 week 6 equivalent to the values in the AML and FZR treatment
140
groups.
120
ALT (IU/L)

100
80
60
40
20
0
Group 1 Group 2 Group 3 Group 4 Group 5
250
week 2 week 4 week 6
200
ALP (IU/L)

150
Figure 7. Total protein concentration in zidovudine
100
induced rats treated with extracts of Annona muricata
leaves and Fagara zanthoxyloide roots
50

0
Group 1 Group 2 Group 3 Group 4 Group 5

Figure 4-6: Liver enzyme activity (IU/L) in zidovudine


induced rats treated with extracts of Annona muricata
leaves and Fagara zanthoxyloide roots.

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts of Annona Muricata Leaves and Fagara Zanthoxyloide Roots on Zidovudine-Induced Wistar Rats
Int. J. Toxicol. Environ. Health 049

Figure 8. Albumin concentration in zidovudine induced


rats treated with extracts of Annona muricata leaves and
Fagara zanthoxyloide roots Figure 10. Bilirubin concentration in zidovudine induced
rats treated with extracts of Annona muricata leaves and
Fagara zanthoxyloide roots
The decrease in the concentration of total protein, albumin
and globulin in the negative control (Group 2) when The bilirubin concentration (Figure 10) was observed to
compared to the control suggest that ZDV may induce increase on the administration of ZDV (Group 2) when
hepatotoxicity (George, 2009) resulting in increase compared to the normal control while simultaneous
amounts of p-proteins or decreased antibody production, administration with AML and FZR extracts (Groups 4 and
causing nephrosis and acute hemolytic anaemia (Ekam 5) resulted in significant reduction (p≤0.05) in the bilirubin
and Udosen, 2012). The increase in the concentrations of concentration at week 2 when compared with the negative
these liver biochemicals in AML and FZR treatment groups control and further reduction as time progressed. The
may buttress publications that these extracts possess increase in the level of bilirubin may be possibly caused by
hepatoprotective potentials mediated by antioxidants in an increase in haem metabolism (Amadiet al., 2018) as
Wistar rats (Ekere et al., 2019). bilirubin has been observed to accumulate from the
10 breakdown of haemoglobin, a key component of red blood
9 Group 1 Group 2 Group 3 Group 4 Group 5 cells (Imafidon and Okunrubo, 2012). It may also be a sign
of hepatotoxicity displayed as impairment in the excretory
8
function of the liver or a compromise in its overall
7 functioning as the liver is responsible for the removal of
Globulin (g/L)

6 bilirubin from the blood and excreting it through the bile


5 (Senou, et al., 2017).
4
The serum concentrations of urea and creatinine in the
3
negative control group (Table 1) were observed to
2
significantly reduce (p≤0.05) on administration of ZDV in
1 group 2 when compared with the normal control. However,
0 the simultaneous administration with extracts of AML and
week 2 week 4 week 6 FZR resulted in a significant increase (p≤0.05) in the
serum concentrations of urea and creatinine at week 2, 4
Figure 9. Globulin concentration in zidovudine induced and 6.
rats treated with extracts of Annona muricata leaves and
Fagara zanthoxyloide roots

Table 1: Kidney indices in zidovudine-induced rats treated with extracts of Annona muricata leaves and Fagara
zanthoxyloide roots.
GRP Urea (mmol/L) Creatinine (µmol/L)
Week 2 Week 4 Week 6 Week 2 Week 4 Week 6
Group 1 5.69±0.20a 5.69±0.20a,b 5.69±0.20c 39.70±0.16a 39.70±0.16a,c 39.70±0.16c
Group 2 4.57±0.18b,c 4.15±0.02a,b 4.08±0.20a,c 30.35±0.01a 28.15±0.03a,d 24.34±0.04a,c
Group 3 5.24±0.28e 5.15±0.04a,d 4.94±0.03c,d 48.61±0.17a,c 46.13±0.03e 44.91±0.23a,e
a,d c a,e a b,c
Group 4 5.34±0.02 5.47±0.05 5.56±0.30 46.42±0.02 50.14±0.03 53.39±0.01a,b
c,e b,c c b.e b
Group 5 5.31±0.03 5.37±0.02 5.44±0.03 49.01±0.04 50.07±0.08 52.14±0.04a,e
Values expressed as Mean ± SEM of triplicate determination. Values with same superscript are statistically significant
(p≤0.05).

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts of Annona Muricata Leaves and Fagara Zanthoxyloide Roots on Zidovudine-Induced Wistar Rats
Ekere et al. 050

The urea and creatinine concentrations have been transversing the liver and alterations in the architecture of
reported to serve as reliable markers of the functionality of the hepatocytes which progressed towards necrosis and
the kidney (Belonwu et al., 2013), as such the decrease in sinusoidal infiltrations at week 6 (Plates 2-4).
the concentrations would signify that ZDV results in a
decrease in the optimal functionality of the kidney possibly
resulting in nephrotoxicity as reported by Amadi et al.,
(2018). The increase in the serum urea and creatinine
concentrations on administration with extracts may
suggest that the extracts of AML and FZR prevent
nephrotoxicity induced by ZDV by a mechanism not
explored in this study (Ogunnka-Nnoka et al., 2012).

Histological examination

An examination of the liver of group 1 showed the


hepatocytes in normal architecture radiating from the Plate 1. Liver of normal control group showing
portal triad (Plate 1). Administration of 100mg ZDV/Kg B.W hepatocytes arranged in rolls radiating from the portal triad
resulted in severe dilation, congestion of blood vessel along with a few dilated hepatic veins

Plate 2. Liver of Negative control group at Plate 3. Liver of Negative control group at Plate 4. Liver of Negative control group at
week 2 showing severe dilation and week 4 showing dilation and portal vein week 6 showing marked sinusoidal congestion
congestion of blood vessels with altered congestion and necrosis
architecture

Treatment with AML showed hepatocytes with preserved suggest that ZDV may induce hepatic damage at the
architecture when compared with the negative control. dosage administered .According to Akinnawo et al.,
Slight dilation in the hepatic cords and single cell necrosis (2005), the architecture for the group administered with
was also observed on prolonged administration with AML AML may signify that the extract confers hepatoprotective
(Plates 8-10). Prolonged FZR administration resulted in abilities through the presence of several antioxidants
hepatic regeneration at week 4 with a decrease in hepatic (alkaloids, phenols, tannins), anti-inflammatory agents
infiltration and congestions observed at week 6 (Plates 12 (norchelerythine, α-humlene, β-pinene, zinc, fiber),
and 16). myleoregenerative and tissue regenerative agents (amino
acids, zinc, calcium, folate, vitamin B12) as seen in Plate 8-
Sinusoidal congestion and dilations have been reported by 9 (Ekere et al., 2019, Adisa et al., 2014.The observations
Adisa et al., (2014) as an important marker of early onset in the group administered with FZR may also signify a
hepatotoxicity. The necrosis observed in the negative regression in the observed deleterious effects of ZDV on
control group serves as a sign of hepatic degeneration, administration indicating a protective effect conferred on
which in combination with the aforementioned signs may the hepatocytes by the extracts.

Plate 5. Liver of group 3 at week 2 Plate 6. Liver of group 3 at week 4 Plate 7. Liver of group 3 at week 6
showing congestion and dilatation in showing hepatocytic dropout and showing hyalinization and
blood vessels. formation of rosette. progressive lymphocytic infiltration.

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts of Annona Muricata Leaves and Fagara Zanthoxyloide Roots on Zidovudine-Induced Wistar Rats
Int. J. Toxicol. Environ. Health 051

Plate 9. Liver of group 4 at week 4 Plate 10. Liver of group 4 at week 6


Plate 8. Liver of group 4 at week 2 showing distorted hepatic cord. showing single cell necrosis and
showing preserved architecture and esinophilic infiltration.
slight blood sinusoid dialation.

Plate 11. Liver of group 5 at week 2 Plate 12. Liver of group 5 at week 4 Plate 13. Liver of group 5 at week 6
showing normal architecture with showing hepatic regeneration showing decrease in hepatic
focal vocalization infiltration and congestion

The kidney of the normal control group showed normal observed at the epithelium of the renal tubules. The co-
architecture especially with the renal corpusles, tubules administration with extracts of AML and FZR resulted in
and connecting ducts (Plate 14). The administration with the kidneys displaying normal architecture but with slight
ZDV resulted in hypoplasia of the cells with swellings dilations observed in the glomeruli.

Plates 14. Kidney of group 1 showing kidney cortex with normal structure of renal corpuscles, renal tubules and collecting ducts

Plates 15, 16, 17. Kidney of group 2 at week 2, 4 and 6 showing glomerulus was observed to be hyperplastic with renal
tubules epithelium showing signs of swellings

Plates 18, 19, 20. Kidney of group 3 at week 2, 4 and 6 showing collecting tubules lined with the relatively low simple
cubic epithelium.

Hepatotoxicity and Nephrotoxicity Studies of Ethanol Extracts of Annona Muricata Leaves and Fagara Zanthoxyloide Roots on Zidovudine-Induced Wistar Rats
Ekere et al. 052

Plates 21, 22, 23. Kidney of group 3 at week 2, 4 and 6 showing normal architecture except in few spots of slight
dilation of glomeruli with medullary hyperaemia

Plates 24, 25,26. Kidney of group 3 at week 2, 4 and 6 showing Henle’s loop showed thick descending with small
amount of interstitial cells as well as collecting coils of small calibre

Hyperplasia observed in the negative control group has cariogenic and enteric bacterial isolates. Journal of
been linked to a regression in the development of the Intercultural Ethnopharmacology 1(1):1-6
kidney cells and reported by Adewole et al., (2006) as an Adewole S.O., Caxton-Martins E. A. (2006). Morphological
early sign of renal adaptations to toxins and possibly changes and hypoglycemic effects of Annona muricata
nephrotoxicity. The normal architecture observed on co- leaf aqueous extract on pancreatic β-cells of
administration with AML may further buttress the findings streptozotocin-treated diabetic rats. African Journal of
of Ekere et al., 2019 which suggested that the extracts Biomedical Research 9:173–187.
contained anti-oxidative agents (alkaloids, tannins, Adisa, O.I., Belonwu, D.C. ,Oghenekaro, U.E ., Odeghe,
phenols) and anti-inflammatory agents (norchelerythine, O.B. (2014). Effect of selected Yoruba medicinal
α-humlene, β-pinene, zinc, fiber) which confer some formulations on hepatic architecture and functionality in
degree of protection to developing kidney cells hence wistar albino rats. Global Journal of Research on
imitating nephroprotectivity. Medicinal Plants & Indigenous Medicine 3(9):331–338
Akinnawo, O.O., Taiwo, V.O., Ketiku, A.O. and Ogunbiyi,
J.O. (2005). Weight changes and organ pathology in
CONCLUSION rats given edible larvae of Cirina forda (westwood).
African Journal of Biomedical Research, 8:35 – 39
The administration of zidovudine resulted in hepatotoxicity Al-Hasawi and Al-Harbi (2014). Effect of Rhazya stricta
and nephrotoxicity which were observed to be reduced to dense leaf extract on the liver and kidney tissue
some degree when extracts of AML and FZR were structure of albino mice. Global Advanced Research
administered as seen with the results of histological Journal of Environmental Science and Toxicology.
investigations and liver and kidney indices investigated. 3(4):057-064.
The impact of the extracts on these liver and kidney indices Amadi, P.U., Agomuo, E.N., Bob-Chile Agada, A.I., Njoku,
and body and organ weight may suggest that these plants A.I. et al., (2018). Toxicities of selected medicinal plants
may be hepatoprotective and nephroprotective to some and floras of lower phyla. Alexandria Journal of
degree and may also be used in anorexigenic conditions Medicine 54:587–596
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