ABSTRACT
Increased oxidative stress arising from the maternal hyperglycemic-induced disturbances in fetal metabolism has been suggested to play a role in the pathogenesis of disturbed embryogenesis in diabetic pregnancies. Maternal diabetes in pregnancy and the associated hyperglycemia is also believed to expose the fetus to disturbed metabolic conditions in-utero creating a ‘metabolic memory’ that programs the fetus for glucose intolerance, diabetes mellitus and obesity later in life. Bitter kola (Garcinia kola) is a medicinal plant with a wide range of pharmacological effects including ant diabetic and antioxidant effects. In this study, the effects of aqueous extracts of Garcinia kola seed on the pregnancy outcome and early postnatal development of the offspring of pregnant alloxan diabetiPc and non-diabetic Wister rats was studied. Forty (40) nulliparous female Wister rats were used. Pregnancy was induced in all the rats, and diabetes induced in twenty (20) making two groups; pregnant diabetic and pregnant non-diabetic. These two groups were further subdivided into four groups of five rats each receiving different concentrations of the extract as follows; control, 100mg, 200mg, and 300mg/kg of body weight. The extract was administered orally as a single dose daily throughout gestation. The extract caused a reversal of the significant reduction of weight gain and significantly increased weight gain among the pregnant diabetic rats. It also significantly reduced the fasting blood glucose concentration in the hyperglycemic diabetic rats in a dose-dependent manner to values close to normal. These may be due to the insulinogenic effect of kolaviron an active principle of Bitter kola The extract significantly increased the litter size among the diabetic pregnant rats in a dose-dependent manner when compared with their control that showed a statistically significant reduction in litter size. This observed effect of the extract may be because of the anti-oxidative stress effects of kolaviron and ascorbic acid (constituents ofBitter kola) observed in previous studies. The extract also reduced the birth weight, excessive early post natal growth, and the high fasting blood glucose concentration on the weaning (21st) day, among the offspring of diabetic rat in a dose-dependent manner when compared with those of the diabetic pregnant control group. These may be due to the blood glucose lowering effect of the aqueous extract of Bitter kola seed among their mothers which leaves little or no excess glucose for the fetus to absorb and as such avert the major complications of diabetic pregnancy. The result of this study suggests that Bitter kolamay have a protective effect against the adverse effects of diabetes in pregnancy on both the mother and the offspring.
CHAPTER ONE
INTRODUCTION
1.1 INTRODUCTION
Compelling evidence
suggests that exposure to an adverse fetal environment may enhance
susceptibility to a number of chronic diseases in the future life of the
offspring(Buzinaro et al, 2008; Simeoni and Barker, 2009).
Diabetes mellitus is a condition that
occur during pregnancy that can substantially influence the development of the
offspring in utero and postnatally. Diabetes mellitus
is now a pandemic, affecting about 10million Nigerians (Ogbera et al, 2005) and about 350 million
people worldwide (Ezzati et al, 2011)
among who are pregnant women. It is well documented that the combined stress of
diabetes mellitus and pregnancy creates a metabolic environment that is often
life threatening to both the mother and the fetus (Freinkel, 1980; Metzger,
1991).
Hence, pregnancy among
women that have pre-existing diabetes or gestational diabetes is associated
with increased rate of adverse outcome for both mother and fetus (Kingsley,
2007; Shefali et al., 2006).
This is primarily due to
altered maternal intrauterine environment, creating a situation in which the
fetus is exposed to abnormal metabolic substrate (glucose) levels (Van Assche et al, 1991). There is an increased
placental transfer of glucose from mother to fetus because of increased
availability at the maternal site (Thomas et
al, 1990). The compromised metabolic state of the fetus subsequently
precipitates a variety of complications associated with ‘‘fuel-mediated
teratogenesis’’ (e.g., hyperglycemia, hyperinsulinemia and macrosomia)
(Freinkel, 1980; Metzger, 1991). One particularly devastating effect of
diabetic pregnancy is that these conditions affect the fetus not only in utero,
but also extend throughout the life of the offspring (Padilha et al, 2007; George et al, 2010). Additionally, maternal hyperglycemia stimulates
abnormal fetal growth (Aberg et al,
2001) due to the greater availability of glucose in the blood flow
(Maayan-Metzger et al, 2009), and
this high weight fetus carries a high risk for 17
developing insulin resistance,
glucose intolerance, obesity, and type 2 diabetes mellitus in childhood,
adolescence and adulthood (Buzinaro et al,
2008; Simeoni and Barker, 2009)
The chances of reducing
this poor outcome of pregnancy among diabetics are intricately related with the
level of glycemic control (Shefali et al.,
2006).
The fact that the
economic cost of managing diabetes mellitus is high confers a very important
role to medicinal plants in the management of diabetes mellitus especially in
developing countries where resources are meager.
Consequently, a number
of plants indigenous to Nigeria have been studied, and found to have
hypoglycemic effects. These effects were traced to phytochemicals like
alkanoids called active principles that can be extracted from plants(Ojewale,
2006; Osadebe et al., 2004). One of
such anti-diabetic plants is Garcinia
kola, commonly known as Bitter kola. It is an evergreen tree, indigenous to
sub-Saharan Africa and belongs to a family of tropical plants called Guttifera
(Ofusori et al., 2008). The seed is a
masticatory, used for traditional hospitality in cultural and social
ceremonies. Every part of the plant has shown to be of medicinal importance and
has a wide range of medicinal effects, hence the name ‘wonder plant’ as it is
commonly called.
Among the litany of its
medicinal effects are; antidiabetic effects (Iwu et al, 1990), weight reducing effets (Koshy et al., 2001), leptin like action (Hayamizu et al., 2003), antihepatotoxic effects (Akintonwa and Essien,
1990), antioxidative stress and anti DNA 18
damage (Farombi, et al., 2004), detoxification of the
toxic effects of other chemicals (Esimone et
al., 2002; Nwokocha et al, 2011),
etc.
1.2
JUSTIFICATION FOR THE STUDY
Diabetes mellitus is
fast becoming the most common type of disease in school children (Pontiroli,
2004). This may be as a result of the reported more than doubling in therate of
diabetes among expectant mothers between 2002 and 2008 (Lawrence et al., 2008).
The economic cost of
managing diabetes is high. As a result, in the developing countries where
resources are meager, there is a shift from contemporary to orthodox medicine
since medicinal plants are relatively easier to find and less expensive
alternative.
Coincidentally, some of
the commonly consumed plant materials in Nigeria have been found to poses
anti-diabetic properties. One of such anti-diabetic plantmaterials Bitter kola
seed is used as a stimulant. It is also taken by pregnant women to stop nausea.
Although Bitter kolaseed is a known anti-diabetic, there is
paucity of data on;
(1) Its effects on
pregnancies complicated by diabetes mellitus
(2) Early postnatal
development of the offspring’s of such pregnancies.
Hence, the present study
was therefore designed to investigate these.
1.3 AIM
The aim of this study is
to determine the effect of consumption of Garcinia
kola extract by diabetic pregnant rats on the pregnancy outcome and early
postnatal development of their offspring.
1.4 OBJECTIVES
To determine the effect
of consumption of Bitter kolaextract
by diabetic pregnant rats on;
i. The litter size.
ii. The early postnatal growth of the offsprings
(from birth to weaning).
iii. The glucose profile of the offsprings at
weanin
1.5 OPERATIONAL DEFINITION OF TERMS
Alloxan diabetes: A
type of diabetes induced in rodens by the injection of alloxan hydrate. 20 Pregnancy weight gain: The weight gain
during pregnancy.
Programming: The process whereby a stimulus or stress at a
critical period of development of the rats results in a lasting or lifelong
effect.
Teratogenic: Capable of causing developmental abnormalities
in the fetus
Diabetic pregnancy: Pregnancy complicated
by diabetes mellitus irrespective of the type.
Early Postnatal development: This is the
developmental processes that occur in the offsprings from the time of birth to
the weaning day.
Gestation period: The period (in days)
between the time when spermatozoa were first seen in vaginal smear and the time
of delivery.
Glucose drain: The transfer of glucose
from the maternal to fetal blood.
In-utero: Events occurring inside the uterus.
Litter Size: The
number of offspring delivered by a pregnant rat.
Litter weight: The weight of the
offsprings at birth (g).
Perinatal: Events that occur around the time of birth.
Pregestational (Pre-existing) diabetes: Diabetes
existing before pregnancy, irrespective of the type.
Pregnancy weight gain: The weight gain during
pregnancy.
Programming: The process whereby a stimulus or stress at a
critical period of development of the rats results in a lasting or lifelong
effect.
Teratogenic: Capable of causing developmental abnormalities in the fetus..
EFFECTS OF AQUEOUS EXTRACT OF BITTER KOLA (GARCINIA KOLA) ON THE PREGNANCY OUTCOME AND EARLY POSTNATAL DEVELOPMENT OF THE OFFSPRINGS OF DIABETIC
