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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