Journal of Pharmacognosy and Phytotherapy Vol. 3(1), pp.

6-12, February 2011

Available online at http://www.academicjournals.org/jpp
ISSN 2141-2502 ©2011 Academic Journals

Full Length Research Paper

Exposure to smoke extract of Datura stramonium leaf:

Some of its effects on the heart, liver, lungs, kidneys
and testes of male Sprague Dawley rats
Adekomi D. A.1*, Tijani A. A.2, Adeniyi T. D.2, Musa A. A.1 and Usman B.3
1
Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria.
2
Department of Anatomy, College of Health Sciences, Osun State University, Osogbo, Nigeria.
3
Center for Anatomy and Human Identification, College of Life Sciences, University of Dundee, Dundee, Scotland,
United Kingdom.
Accepted 6 May, 2011

Smoking has been recognized as a significant contributor to mortality. The aim of this study was to
evaluate some of the toxic effects of smoke extract of Datura stramonium leaf on the heart, liver,
kidneys and testes of male Sprague Dawley rats. A total of ten male Sprague Dawley rats weighing
between 100 and 120 g were used for this study. The animals were randomly assigned into two (2)
groups; A and B. Animals in group B (treatment group) were exposed to smoke from a completely burnt
0.74 g leaf extract of D. stramonium, wrapped in 0.5 g of sterilized cotton wool for 5 min, three times
daily. The animals in group A (control group) were exposed to smoke from completely burnt 1.24 g of
sterilized cotton wool with the same parameters as observed with the treatment groups. The duration of
exposure was for five days. 3 h after the last exposure, all the animals were sacrificed by cervical
dislocation. The heart, liver, lungs, kidneys and testes were carefully excised, blotted dry, and fixed in
formol saline for histological analysis using Hematoxylin and Eosin (H and E) stain. Using the light
microscope, it was observed that, the cytoarchitectural profiles of the studied organs were well
preserved in the animals in the control group. However, several histological deviations were seen in the
sections of the heart, liver, lungs, kidneys and testes of the animals in the treatment group. These
deviations range from distortion and degeneration of the hepatocytes, reduction in the population of
the germ cells and enlargement of the alveoli. These histological deviations indicated that the smoke
extract of D. stramonium leaf has deleterious effects on the heart, liver, lungs, kidneys and testes of
male Sprague Dawley rats and may be associated with structural damage to these vital organs.

Key words: Cotton wool, Datura stramonium, histological deviations, kidneys, liver, testes.

INTRODUCTION

The medicinal plant Datura stramonium is often used as have reported that D. stramonium extract is especially
an analgesic plant in folklore medicine in the “Old world” rich in alkaloids (Hasan and Kushwaha, 1987; Piva and
(Zargari, 1989). The plant has also been used as a Piva 1995).
narcotic and local anesthetic drug in many societies The alkaloid content of D. stramonium has been
(Schulman and Bolton, 1998; Abena et al., 2003; Arouko emphasized by the phytochemical investigators dealing
et al., 2003). In some nations, young people in quest for with the biochemical composition of various parts of the
cheap hallucinate, uses its leaves by smoking for plant. Atropine, hyoscyamine and scopolamine
hallucination purpose in order to make them “high” (hyoscine) are the tropane alkaloids of all species of the
(Schulman and Bolton, 1998). Some scientific investigations genus Datura and their concentrations showed variations
depending on species and on the part of the plant
(Checke and Shull, 1985; Duez et al., 1985; Ren- sheng
et al., 1985). Duke (1992a) presented data on concentra-
*Corresponding author. E-mail: [email protected] Tel: tion of total alkaloids in leaves and flowers of D. metel
+23480-3844-1671, +23480-7656-3746. (Hindu datura) , D. stramonium (Jimson weed) a nd
D. innoxia (Thorn apple). The emphasis on tropane synthesis and release (Ganong, 1999; Junqueira et al.,
alkaloids is due to their importance in pharmaceutical 1998).
industry. Proteins, fats, fatty acids, reducing sugars, The testis, which is the major male reproductive organ,
oxalates, nitrates and tannin are among the chemical is responsible for sperm production. It is suspended in
entities that have been described in the plant (Duke, the bilateral compartments of the scrotal sac. Production
1985; Hussein, 1985). Chlorogenic acid, an anti- of spermatozoa from stem cells of the testis is a complex
histaminic, an allantoin, an immunostimulant (Duke, process that requires about 64 days in human (Heller
1992b), Lectin agglutinin, a glycoprotein (Russel et al., and Clermont, 1964) and about 48 to 53 days in rat
1997; Pla, 2003), gamma amino-butyric acid, a (Clermont, 1972; Hilscher, 1964). The sertoli cells play a
hypotensive and neuro-inhibitor (Friedman and Levin, vital role in spermatogenesis (Sapori, 1986; Sharpe,
1989), are within the list of the active ingredients present 1993), whereas, leydig cells are the main source of
in D. stramonium. Measurable amounts of 27 metal ions androgen production (Al-Hazmi, 2005). Both types of
have also been detected (Williams and Rayson, 2003). cells can be adversely affected by toxins and chemical
The heart is a muscular organ present in all drugs (Spielman, 1998; Papadakis, 1999). Also, an
vertebrates. It functions in the pumping of blood through alteration in the functional integrity of these cells may
the blood vessels in a repeated contracting rhythm lead to a deleterious compromise in the hormonal
(Heath, 1999). The heart of a vertebrate is made up of balance, or may disturb the process of spermatozoa
cardiac muscle known as the myocardium, an involuntary development and may ultimately cause impaired male
muscle tissue which is found only within this organ. The fertility (Monsees, 2000, 2001).
myocardium is the heart's muscular wall (Heath, 1999). It These vital organs have the capability of carrying out
contracts to pump blood out of the heart and then relaxes several essential functions in the body and which if
as the heart refills with returning blood. Its outer surface compromised in any form and/or way, may be absolutely
is called the epicardium. Its inner lining is the deleterious to the body.
endocardium (Heath, 1999). This study was done on animal models because it is
The liver is the second-largest largest organ in the not ethical and practical to perform such an investigation
mammalian body. It has a peculiar macro- and micro- with human subjects. The most suitable model to use is
morphology. The micro-morphology consists of lobules one which is closely related to humans. Keeping these
and sinusoids that are lined with active phagocytes points in view, the study was performed on male Sprague
known as the Kupffer cells; central portal veins and Dawley rats, as they are easy to breed and rear and they
hepatocytes plates that are closely associated with the can as well be handled with ease. According to the U.S.
terminal lymphatics and bile canaliculi (Webster and Department of Health and Human Services (2004), the
Webster, 1974; Lesson et al., 1988; Berne and Levy, body produces antioxidants that helps repair damaged
1998; Costanzo, 1998). These distinguishing morpholo- cells. Smokers have lower levels of antioxidants in their
gical features enable the liver to carry out a wide range of blood than do nonsmokers. Smoking is associated with
essential functions such as filtration, secretory and higher levels of chronic inflammation, another damaging
excretory functions and processes. The hepatocytes process that may result in oxidative stress.
have metabolic functions that deal with very crucial The components of smoke are complex and vary
processes such as detoxification, deamination, transa- considerably in relation to conditions of incomplete
mination, removal of ammonia in the form of urea, combustion, the combustion materials, temperature,
biosynthesis and release of the non-essential amino circumstances and timing (Xie et al., 1998), and since
acids and plasma proteins. Approximately 15% of the smoking has been recognized as a major contributor to
adult life erythropoietin is synthesized by the hepatic mortality in man, previous studies have confirmed the
Kupffer cells and hepatocytes (Binkley, 1995; Griffin and effects of tobacco and/or marijuana exposure on the
Ojeda, 1996; Ganong, 1999). brain, nervous system and the general body system
The functional and structural unit of the kidneys is the (Dagher et al., 2001; DiChiara et al., 1992; Pfaus et al.,
nephron. Kidneys of the mammalian species show 1990), but search for available literature on the effects of
variations in the ratios of the cortical and juxtamedullary the smoke of D. stramonium on the heart, liver, lungs,
nephrons but have in common, a unique structural kidneys and testes in laboratory animals is not available.
characteristic that is the presence of two capillary Hence, the present study is aimed at investigating some
networks: the glomerular and the peritubular structures. of the effects of the smoke extract of D. stramonium leaf
The endothelial cells of the peritubular capillaries have as a marker of toxicity on the histology of the heart, liver,
endocrine activity, which is represented by synthesis and lungs, kidneys and testes of male Sprague Dawley rats.
release of the erythropoietin hormone. The granular
juxtaglomerular cells of the afferent glomerular arterioles MATERIALS AND METHODS
as well as the agranular lacis cells in the junction
between the afferent and efferent glomerular arterioles Collection of plant and preparation of plant extracts
are the specific cells that are responsible for renin The sample of D. stramonium used was obtained from the botanical
 0.1 m3 volume (38 × 88 × 30 cm) (Onarlioglu et al., 1999) was also
used. In the upper surface of the chambers, an opening of 1 cm
was made (Onarlioglu et al., 1999). The chambers were designated
as A and B respectively. The animals in group B were placed in
chamber B and were exposed to smoke extract of D. stramonium
leaf by inhalation (0.74 g leaf of D. stramonium wrapped with 0.5 g
of refined and sterilized cotton wool for 5 min three times daily;
7am, 10am, and 1pm) for 5 days. The animals in group A were
placed in chamber A and were exposed to the same amount of
refined sterilized cotton wool three times daily (7am, 10am, and
1pm) for 5 days.

Animal sacrifice

Three hours after the termination of investigation, the animals were

sacrificed by cervical dislocation (Adekomi, 2010), but the heart,
liver, kidneys and testes were carefully excised from the animals,
rinsed in cold sucrose solution and blotted dry with filter paper. The
liver, lungs and heart were fixed in separate specimen bottles
containing 10% formol-saline while the kidneys and testes were
quickly transferred into a specimen bottle containing Bouin’s fluid.
Thereafter, the fixed specimens were removed from the fixatives in
order to process for further histological analysis.

Histological parameters

Figure 1. Photomicrograph of the heart of the animals in the Histological studies on the heart, liver, lungs, kidneys and testes
treatment group showing mild edema and destruction of were done according to the procedures described by Disbrey and
myocardial fibers (H&E × 480). Rack (1970) and Drury and Wellington (1967). The sections were
subjected to Hematoxylin and Eosin (H and E) staining procedures
and the histological examination was done with the aid of the
Olympus binocular light research microscope (XSZ-107BN, No.
garden of the University of Ilorin, Ilorin, Kwara State, Nigeria. 071771). The permanent photomicrographs of each slide were
Botanical identification was done at the Department of Plant recorded with a Kodak digital camera (Kodak Easyshare C183) for
Science, University of Ilorin, Nigeria. The leaves of the plant were subsequent histological analysis.
air-dried under shade without sunshine. The dried plant material
were weighed using Gallenkamp (FA2104A, England) electronic
weighing balance and 0.74 g of the plant sample was later wrapped RESULTS
with 0.5 g of refined and sterilized cotton wool.
No morphological alterations were observed in the
Animal care morphology of the heart, liver, lungs kidneys and testes
of the animals in both groups (A and B) sacrificed (3 h)
This experimental investigation was done in accordance with the after the termination of experimental procedure. The
standard humane animal care as outlined in the “Guide for the care excised heart, liver, lungs, kidneys and testes of the
and use of Animals in research and teaching”, as approved by the animals in both groups appeared morphologically normal.
Institute of Laboratory Animal Resource, National Research
Histological assessment of the heart of the animals in the
Council, DHHS, Pub. No NIH 86 – 23 (NIH, 1985). The study was
carried out using 10 presumably healthy male Sprague Dawley rats treatment group showed significant abnormal alteration in
weighing between 100 and 120 g. All the animals were housed in the histological profile when compared with that of the
clean cages of dimensions 33.0 × 20.5 × 19.0 cm placed in well animals in the control group. Some of the histological
ventilated standard housing conditions (12 h light and 12 h deviations include; marked edema and destruction of
darkness; temperature: 28 to 31°C; humidity: 50 to 55%) (Yakubu, myocardial fibers (Figures 1 and 2).
2008) and their cages were cleaned everyday. All animals were
observed for illness, abnormal behavior and physical anomalies.
The histological profile of the kidneys section of the
The rats were fed with standard rat chow at a recommended dose animals in the treated group exposed to the smoke
of 100 g/kg as advised by the International Centre of Diarrhoea extract of D. stramonium leaf showed significant
Disease Research, Bangladesh (ICDDR, B) daily. Drinking water degenerative changes. In the renal cortex, there was
was supplied ad libitum. shrinkage of the glomerulus and progressive death of the
cells in the epithelial lining of the tubular system of the
kidneys (Figures 3 and 4).
Experimental design
The histological outline of the lungs of the animals in
In this study, 20 male Sprague Dawley rats weighing between 100 the treatment group revealed significant cytoarchitectural
and 120g were used. Two closed glass chambers of approximately alteration and/or disruption. Though the smooth muscle
 Figure 3. Photomicrograph of the Kidneys of the
animals in the treatment group showing
progressive death of the epithelial cells lining the
convoluted tubules (H & E × 480).
Figure 2. Photomicrograph of the heart of the animals in
the control group (H&E × 480).

In this investigation, we examined some of the effects

of the smoke extract of D. stramonium leaf on the heart,
layer of the bronchi was preserved, there is still an liver, lungs, kidneys and testes of male Sprague Dawley
enlargement of the alveoli and the alveoli sacs (Figure 5 rats. Evidence from this investigation through the use of
and 6). the Olympus binocular light microscope (XSZ-107BN, Nọ.
The histological outline of the liver section in treatment 071771), showed that the smoke extract of D.
group does not conform to normal histological profile. stramonium leaf has adverse and severe effects on the
Some of the histological alterations observed include histology of the heart, liver, lungs, kidneys and testes of
degeneration, and progressive death of the hepatocytes, male Sprague Dawley rats when compared with the
and occlusion of the central portal vein. Using a control animals.
stereological grid (Caroline et al., 2003), it was also The massive enlargement of the alveoli and bronchiolar
observed that the populations of the sinusoidal lining cells occlusion could have been a result of direct toxicity or
are few and scanty (Figure 7 and 8). could have resulted from transportation of toxic
Sections of the testes of the animals in the treatment substances from other organs like the liver and kidneys to
group revealed histological disruption and cellular the lungs. The section of the liver, kidneys and testes
derangement such as degeneration of the germ cells in obtained from the treatment group has disrupted
the seminiferous tubules and also the degeneration of the histological organization compared with the control group.
leydig cells. Other effects such as cytoarchitectural Some of the deleterious effects seen in the section of the
distortions and vacuolations are evident in the section of liver obtained from the treatment group include degene-
the testes of the animals in the treatment group (Figure ration and disruption of the hepatocytes, degeneration of
9). the cells lining the bile ducts and occlusion of the central
portal vein. With these histological abnormalities, the
anatomical, physiological and biochemical functions of
DISCUSSION the liver could be compromised. It is known that the
hepatocytes play a vital role in the proper functioning of
Several scientific literatures have discussed some of the the liver as the hepatocytes are the main functional cells
effects of aqueous and ethanolic leaf extracts of D. of the liver. The hepatocytes frequently contain glycogen
stramonium on the laboratory animals (Gidado et al., and the hepatocytes maintain a steady level of blood
2001; Guharov and Barajas, 1991; Anozie, 1986). glucose. This is one of the main sources of energy for
However, there is dearth of scientific literature on the use by the body (Stevens and Lowe, 2005; Junqueira
effects of D. stramonium on the histology of the heart, and Carneiro, 2003). A compromise in the integrity of the
liver, lungs, Kidneys and testes of male Sprague Dawley hepatocytes could lead to improper functioning of the
rats as a marker of toxicity. liver.
 Figure 4. Photomicrograph of the Kidneys of the Figure 6. Photomicrograph of the lungs of the
animals in the control group (H&E × 480). animals in the control group (H&E × 480).

Figure 5. Photomicrograph of the lungs of the

animals in the treatment group showing enlarged Figure 7. Photomicrograph of the liver of the
alveoli and alveoli sacs (H&E × 480). animals in the treatment group showing
distortion, degeneration and progressive death
of the hepatocytes and also the occlusion of the
portal vein. (H&E × 480).

The tubular structure of the renal cortex of the animals

in the treatment group exposed to the smoke extract of D.
stramonium leaf showed disruption in the histological unavoidable side effects of so many drugs (Haschek and
make up of the organ. Varying degrees of vacuolation Rousseaux, 1998; Baylor and Williams, 1999; Fored,
were also seen in the proximal convoluted tubules which 2001; Mackinnon et al., 2003; Holland and Degruy,
may compromise the functional integrity of the brush 1997). Renal damage has been reported as a side effect
border. These characteristics may lead to the retention of to the administration of many medications (Chang et al.,
waste products of metabolism. Persistence of such 2001; Ono et al., 1998; Lord et al., 1999; McIntyre, 1998;
abnormalities results into loss of the sensitive Reginster et al., 1997). Such damage should reach a
homeostatic functions of the kidneys (Stevens and Lowe, minimal accepted extent, as a side effect, at the end of
2005). Kidneys are also the targets involved in experimentations aimed at determining the extent of
 Figure 8. Photomicrograph of the liver of the
animals in the control group (H&E × 480).

Figure 9. Photomicrograph of the testes of the

animals in the treatment group showing distortion
and gradual reduction in the population of the germ
toxicity under specified conditions of frequency and cells in the seminiferous tubules and also the
duration of treatment. degeneration of the leydig cells (H&E).
Several abnormal histological alterations seen in the
testes of the animals in the treatment group, ranges from
degeneration and disruption of the germ cells lining the
seminiferous tubules, and also the degeneration of the spermatozoa, thus maintaining the nursing capacity of
leydig cells. Reduction in the population of the germ cells the sertoli cells (Sinha and Swerdloff, 1999). However,
was also seen in the histological profile of the testes high levels of ROS disrupt the inner and outer
obtained from the treatment group compared with the mitochondrial membranes, inducing the release of the
control group. The implication of this is that there is a cytochrome-C protein and activating the caspase
reduction of viable sperms which may lead to infertility. cascade which ultimately results in the fragmentation of a
Degenerative changes have been scientifically reported cell's DNA (Wyllie, 1980; Green, 1998; Makker, 2009).
to result in cell death. There are two types of cell death, Cellular necrosis is not induced by stimuli intrinsic to the
namely, apoptosis and necrosis (Cohen, 1993; Vaux et cells as in programmed cell death, but by an abrupt
al., 1994). These two types differs biochemically and environmental perturbation and departure from the
morphologically (Bose and Sinha, 1994). Apoptosis is a normal physiological conditions (Martins, 1978).
non-inflammatory response to tissue damage charac- Smoking may also promote to a greater extent, the risk
terized by a series of morphological and biochemical of dementia via its effect on other medical conditions
alterations (Sakkas et al., 1999; Sinha and Swerdloff, such as coronary disorders (Nilsson et al., 2006), and it
1999; Shen et al., 2002; Grunewald et al., 2005). may interact with other cardiovascular risk factors in a
Apoptosis can be triggered in two principal ways: by toxic synergistic or additive manner (Luchsinger et al., 2005). It
chemicals or injury leading to damage of important cells, may also interact with genetic factors such as
tissues and organs (Schulte-Hermann et al., 1995). apolipoprotein E genotype (APOE) to increase the risk of
Initiation of apoptosis can occur as a result of insults from dementia (Beeri et al., 2006). Smoking cessation is
multiple stimuli, including heat, toxins (drugs), reactive associated with reduced risk of lung cancer (Godtfredsen,
oxygen species (ROS), growth factor withdrawal, 2005), cardiovascular risk (Serrano et al., 2003), and
cytokines such as transforming growth factor- beta, loss cancer (Castellsague et al., 2000).
of matrix attachment, glucocorticoid, nitric oxide, and In this study, smoke extract of D. stramonium leaf may
exposure to huge amount of radiation (Thompson, 1995; have acted indirectly through generation of high levels of
Pollman et al., 1996). These insults functions in ROS or directly as toxin to the cells of the liver and
conjunction with other intrinsic factors that determine the testes, affecting their cellular integrity and causing defect
cell's potential to undergo apoptosis (McConkey and in membrane permeability. In cellular necrosis, the rate of
Orrenius, 1991). progression depends on the severity of the insults. The
The process of apoptosis in the testes in context of greater the severity of the insults, the more rapid the
male reproduction helps in elimination of abnormal progression of the injury. The principle holds true for
 ACKNOWLEDGEMENTS

Authors are deeply grateful to Professor E. A. Caxton-

Martins (FASN) of the Department of Anatomy
(Postgraduate Unit), University of Ilorin, Ilorin, Kwara
State, Nigeria for research guidance and inspiration. We
are thankful to Mr. Mohammed Abdulrasheed Ola of the
Histopathology Department of the University of Ilorin
Teaching Hospital, Ilorin, Kwara State, Nigeria for tissue
processing and to Mr. Adekilekun A.M of the School of
Basic Midwifery, University of Ilorin Teaching Hospital,
Ilorin for providing the Kodak Digital Camera (Kodak
Easyshare C183) used for taking the photomicrographs.

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