ABSTRACT
Arsenite
is an environmental toxicant known to elicit adverse effects on liver and
kidney organs. This study was designed to investigate the protective effects of
Garcinia kola Heckel stem bark
ethanolic extract (EEGK) and triterpenoid fraction (TFGK) against sodium
arsenite-induced hepatotoxicity and nephrotoxicity in rats.
Sodium
arsenite was used to induce hepatotoxicity and nephrotoxicity in Wistar strain
albino rats for 14 days.EEGK and TFGK were used as test samples while silymarin served as a standard drug for comparison. Biomarkers measured were plasma
alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
phosphatase (ALP), urea, and creatinine. Ferric reducing antioxidant potential
(FRAP), 1-1- diphenyl 2-picryl hydrazyl (DPPH), hydroxyl radical scavenging
activity (HRSA), and total antioxidant capacity (TAC) assays were used to
determine the antioxidant activity in
vitro and In vivo antioxidant assays on the liver,
kidney, and plasma superoxide dismutase
(SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) were carried
out. In vitro mitochondrial membrane
permeability transition (MMPT) was carried out. Histopathological examination
of liver and kidney sections were performed and GC-MS analytical method was
used to identify the bioactive compounds present in TFGK and EEGK.
Data
showed that TFGK reduced ALT, AST, ALP activity and total bilirubin while EEGK
reduced plasma creatinine and urea. Furthermore, EEGK elevated DPPH and
hydroxyl radical scavenging activity, FRAP, and TAC when compared with TFGKin vitro. In addition, EEGK elevated
plasma, liver and kidney SOD, GPx, GSH while TFGK modulated hematological markers. Further study showed
thatTFGK inhibited the formation of liver and kidney MMPT.Histopathological
examination showed that TFGK and EEGK reversed sodium arsenite-induced
hepatotoxicity and nephrotoxicity respectively. GC/MS analysis detected 14
bioactive compounds in EEGK and 15 bioactive compounds in TFGK.
The
study concluded that TFGK substantially protected against sodium
arsenite-induced hepatotoxicity than EEGK while EEGKsubstantially protected
against sodium arsenite-induced nephrotoxicity than TFGK. In addition, this
study provided scientific insight to account for the traditional use of G. kola stem bark extract in
ethnomedical practice.
CHAPTER
ONE
INTRODUCTION
1.1 Background to the
Study
Medicinal
plants are a major source of phyto-compounds of beneficial values and are
gaining countless significance in the essential wellbeing of individuals and
social clubs in many nations. They are believed
to be nontoxic
and utilized in the
treatment of numerous diseases, nonetheless, concerns are
drawn to lots of these plants due to their effectiveness, low noxiousness and
absence / minimal adverse effects (Fawole et al., 2010). World Health
Organization (WHO) has defined medicinal plants as plants that contain numerous
properties that could be utilized for restorative purposes or those that
manufacture metabolites to produce suitable drugs (WHO, 2008) .
Contemporary
research has been driven to investigate the effects of numerous medicinal
plants that are believed to possess therapeutic properties for various body
tissues, organs and systems. One of such plants that have gained much attention
is Garcinia kola commonly called
“bitter kola”. G. kola is normally
consumed and used as remedy traditionally for different diseases (Ogunmoloye et
al., 2012). It is vastly cherished for its therapeutic benefits due
to its seed, stem and root serve as raw materials for pharmaceutical usage. The
seed is ordinarily chewed as a masticatory in Nigeria to treat chest colds,
cough, and liver disorders (Yakubu & Quadri, 2012) , also as an emblem
of amity and approval of guests (Otor et al., 2001). The stem bark is
used in traditional medicine for the treatment of dysmenorrhea, inflammation
and scorches (Iwu et al., 1990). The seed of G. kola possess anti-hepatotoxic, hypoglycemic, antioxidant,
hypoglycemic and aphrodisiac properties (Akpanta
et al., 2005) while the stem
bark and root are soaked in local beers and taken orally for fever, cough,
irritation and respiratory tract infections (Gil & Akinwunmi, 1986) .
Sodium
arsenic (NaAsO2) is a toxic metallic pollutant of public health concern that is
present in contaminated drinking water and ground water due to agricultural
spill and mining process (Flora, 2004; Kapaj et al., 2006). In the
environment, inorganic arsenic exist as arsenate (pentavalent, As5+)
and arsenite (trivalent, As3+) and are readily interconvertible in
aquatic environment through redox and methylation reactions. Chandranayagam et
al. (2013) reported that sodium arsenite is sixty times stronger
than sodium arsenate. Molecularly, arsenic is known to induce toxicity and
carcinogenicity through the generation of
oxidative stress and cell reactions as a result of the binding of arsenic to
thiol (SH) groups of macromolecules (Tapio
& Grosche, 2006) . This binding results inalteration of several enzyme activities and
proliferation of harmful reactive oxygen species (ROS) which prompts a wide
array of heavy metal toxicities in human health
(Shi et al., 2004). More so,
the main targets of sodium arsenite induced toxicities are primarily the liver
and kidneys. The most applied therapy for arsenite toxicity treatment has been
metal chelation therapy which forms metal complexes with the consequent removal
of excess arsenite from the body system (Chandranayagam
et al., 2013). This type of therapy
has not been without its adverse effects, however, the utilization of plant extracts as a therapy against metal toxicity with minimal or
no adverse effect could also be considered and scientifically validated.
1.2 Statement of the
Problem
Arsenic
poisoning has been treated with modern-day drugs including silymarin, meso
2,3-dimercaptosuccinic acid (DMSA) and
British Anti-Lewisite (BAL; 2,3-dimercaprol)
which are known to bring about antagonistic impacts to patients.
Numerous conventional healers are known to utilize therapeutic plant extracts
including garlic, curcumin and Moringa oleifera for the treatment of arsenic poisoning. However, there are
little or no scientific information on the hepatoprotective and
nephroprotective effects of G. kola stem bark against sodium
arsenite-induced toxicity. Hence, there is a need to ascertain the therapeutic
potency of G. kola stem bark extract utilized in the management of
sodium arsenite-induced tissue toxicity.
1.3 Objective of the Study
The
main objective is to investigate the hepatoprotective and nephroprotective
effects of G. kola stem bark ethanolic extract and triterpenoid fraction
against sodium arsenite-induced toxicity in rats. The specific objectives are to:
1. determine
the phytochemical constituents in ethanolic extract and triterpenoid fraction
of G. kola stem bark;
2. determine
the antioxidant activity of ethanolic extract and triterpenoid fraction of G. kola stem bark in vitro;
3. investigate
the effects of ethanolic extract and triterpenoid fraction of G. kola stem bark on liver function
markers in rats exposed to sodium arsenite toxicity;
4. investigate
the effects of ethanolic extract and
triterpenoid fraction of G. kola stem
bark on kidney function markers in rats exposed to sodium arsenite toxicity;
5. investigate
the effects of ethanolic extract and triterpenoid fraction of G. kola stem bark on oxidative stress
markers in rats exposed to sodium arsenite toxicity;
6. investigate
the effect of ethanolic extract and triterpenoid fraction of G. kola stem bark on sodium
arsenite-induced mitochondrial membrane permeability transition in liver and
kidney of rats in vitro and;
7. examine
the effects of ethanolic extract and triterpenoid fraction of G. kola stem bark on the histopathology
of liver and kidney of rats exposed to sodium arsenite toxicity.
1.4 Significance of the Study
This investigation
could contribute to the scientific basis on the ethnomedical utilization of G.
kola stem bark in administration of sodium arsenite-induced liver and
kidney toxicities. It could open up opportunities for further research into the
improvement of G. kola stem bark bioactive compounds with a possibility
of developing a new pharmaceutical drug.================================================================
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