Thesis submitted in fulfillment of the requirements for the
Doctor of Technology: Biomedical Technology
In the Faculty of Health and Wellness
At the
CAPE PENINSULA UNIVERSITY OF TECHNOLOGY
2014 / Diabetes mellitus (DM) results in severe metabolic imbalances and pathological changes in many
tissues. Chronic inflammation and oxidative stress have been implicated in the pathophysiology
of diabetes mellitus. Garcinia kola (Family: Guttiferae) is a plant well known for its ample
medicinal values. The seed of the plant also known as ‘bitter kola’ due to its bitter taste is used as
a masticatory agent in traditional hospitality, cultural and social ceremonies in Africa. Kolaviron
(KV) is a defatted ethanol extract from the seeds of Garcinia kola (GK). Kolaviron has been
shown in experimental models of diseases to have numerous beneficial effects due to the
presence of flavonoids (mainly Garcinia biflavonoid (GB)-1, GB-2 and kolaflavanone).
However, there is paucity of information regarding the possible effect of kolaviron on
inflammatory mediators and oxidative stress in diabetes mellitus. Therefore, this study was
carried out to investigate the potential beneficial effects of kolaviron on antioxidant status,
inflammatory mediators and apoptosis. Other biochemical and histological alterations in the
blood, liver and kidney of streptozotocin-induced diabetic rats were also evaluated.
A single intraperitoneal injection of freshly prepared solution of streptozotocin (50 mg/kg.b.wt.)
in citrate buffer (0.1M, pH 4.5) was administered to overnight fasted rats for diabetes induction.
Diabetes was confirmed by stable hyperglycemia (>18 mmol/l) in the tail blood glucose after 5
days of streptozotocin injection. Kolaviron (100 mg/kg b.wt.) was administered to diabetic rats
(by gastric gavage) on the 6th day after the induction of diabetes and treatment continued for 6
weeks (5 times weekly). The effects on blood glucose, body weight, organ (liver and kidney)
weight, serum biochemical parameters, oxidative status, inflammatory mediators and histology
of the liver, kidney and pancreas were assessed.
Kolaviron (KV) treatment lowered blood glucose in diabetic and normoglycemic rats and
reduced glycated haemoglobin [HbA1C (%)]. Plasma insulin level was raised in diabetic rats
treated with KV. Histomorphometric analysis of the pancreas revealed increased β-cell area of
pancreatic islets of kolaviron-treated diabetic group. The indices of organ (liver and kidney)
damage were increased in diabetic rats. However, KV treatment protected against liver and
kidney damage. The characteristic features of diabetic dyslipidemia such as elevated serum
triglyceride and cholesterol concentration which are major risk factors for cardiovascular disease
were also significantly reduced in KV-treated diabetic rats.
Alteration in antioxidant enzymes status was observed in the liver, kidney and blood
(erythrocyte, plasma and serum) of diabetic rats. Lowered catalase (CAT) activity was observed
in the liver and kidney of diabetic rats while KV treatment significantly (p < 0.05) elevated
catalase activity in the liver and kidney. There was no significant change (p > 0.05) in
erythrocyte catalase activity among all treatment groups. Erythrocyte of diabetic rats showed a
marked reduction in the activity of superoxide dismutase (SOD) with no significant changes in
liver and kidney SOD activity of diabetic rats compared to control whereas KV administration to
rats markedly increased SOD activity. Glutathione peroxidase (GPX) activity was elevated in the
erythrocyte and kidney of STZ-induced diabetic rats with no significant effect on liver GPX
activity. KV treatment reversed the alteration in GPX activity in the kidney and erythrocyte.
Level of reduced glutathione (GSH), a non-enzymatic antioxidant was decreased in the both liver
and kidney of diabetic rats and treatment of diabetic rats with KV elevated GSH concentration in
both tissues. Also, malondialdehyde (MDA), a marker of lipid peroxidation was elevated in the
liver, kidney and plasma of diabetic rats and significantly (p < 0.05) lowered following KV
treatment. Diabetes induction reduced the capacity of liver and kidney to absorb oxygen radicals
as demonstrated by lowered oxygen radical absorbance capacity (ORAC) values. KV
administration to normal and diabetic rats significantly increased ORAC values.
Increased rate of apoptosis, a major cellular response to high glucose induced stress was
observed in the renal and hepatic tissues of diabetic control rats. Kolaviron treatment of diabetic
rats protected the liver and kidney against hyperglycemia-induced apoptosis and decreased the
number of TUNEL positive cells
A significant (p < 0.05) elevation of pro-inflammatory cytokines; monocyte chemoattractant
protein (MCP-1), Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor (TNF)-𝛂 was observed
in the liver of diabetes rats. KV treatment lowered these inflammatory biomarkers. On the other
hand, the kidney of diabetic rats showed elevated concentration of pro-inflammatory IL-1β with
no significant effect on kidney TNF-𝛂. An increase in the serum concentration of MCP-1 and
IL-1β was observed in the untreated diabetic rats while kolaviron treatment normalized the
alteration in serum concentration of MCP-1, IL-1β and vascular endothelial growth factor
(VEGF).
In conclusion, persistent and chronic hyperglycemia promotes the generation of free radicals and
inflammatory molecules which contributes to progressive development of micro- and macro
vascular complications and multi-organ damage. Kolaviron demonstrated beneficial effects on
markers of oxidative stress and inflammation in the diabetic rats and also promoted the survival
and functional integrity of the liver and kidney.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:cput/oai:localhost:20.500.11838/1512 |
| Date | January 2014 |
| Creators | Ayepola, Omolola Rebecca |
| Publisher | Cape Peninsula University of Technology |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | http://creativecommons.org/licenses/by-nc-sa/3.0/za/ |
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