Download Assignment on Literature review Submitted by, Ms. Bini

Assignment on Literature review
Submitted by,
Ms. Bini Balakrishnan
079/ July 2012
Department of Physiology,
Yenepoya Medical College.
Topic: Effect of Nigella sativa in Endosulfan induced toxicity in Wistar albino rats
Review of literature:
I. Endosulfan
Pesticides are economically important chemicals and their use in agriculture has increased
crop yields leading to a decrease in food costs. Endosulfan is a widely used insecticide
belonging to the cyclodiene group of organochlorine pesticides1.This chemical is sometimes
found to affect non-target organisms including human, in the course of its application. 2
Reports are available on the physical and chemical as well as toxicological effects of
endosulfan in animals3.Population that are usually susceptible to endosulfan include the
unborn and neonates, the elderly and people with liver, kidney, immunological
haematological or neurological disease 2. Endosulfan is highly toxic, regardless of route of its
exposure 1.causing in-coordination, imbalance, difficulty in breathing, gagging, vomiting,
diarrhoea, agitation, convulsions, loss of consciousness, and central nervous system disorders
2. Chronic exposure results in liver enlargement, seizures, reduced growth and survival,
changes in kidney structure and blood parameters. Endosulfan is known to get excreted from
the mammary gland via the human breast milk in a comparatively higher rate than other
pesticides 1. This is a highly toxic pesticide and a potential endocrine disruptor. Its half-life
ranges from few months to years in soil and 1-6 months in water depending on pH and other
climatic conditions. The Environmental Protection Agency (EPA) has classified endosulfan
as a toxicity class Ib chemical and is a major environmental concern because of its persistent
nature 4. Endosulfan persists in the environment and bio accumulates in animals and plants,
leading to instances of food contamination and eventually dietary exposure in humans 5
II. Endosulfan induced toxicity in experimental animals
In a short term toxicity test of endosulfan on amphibian animal models revealed that low
concentrations can be very highly toxic to amphibians and have suggested that this mortality
may exhibit important lag effects 6. In a recent study they found that sub lethal dose (0.32
ppm/kg-1 bw) of endosulfan after15, 30 and 45 days of exposure to five week of albino rats
resulted in histopathological changes in renal tissue and endosulfan induced severe renal
damages. They concluded that endosulfan is a nephrotoxic chemical and that exposure
produces significant renal toxicity, in rats4. According to a recent study endosulfan decreases
reproductive parameters such as sperm count, motility and testicular weight. The
concentration of hormones such as LH and FSH were significantly more while testosterone
underwent a meaningful decrease. Hence this study found that the above may lead to
infertility due to the changes in sex hormones concentration and sperm count and motility 7.
Following intravenous administration of endosulfan in Sprague–Dawley adult rats under
urethane anesthesia at doses from 0.5 to 4 mg/kg resulted in increase in electro
encephalogram (EEG) power and the evoked potentials (EP) and large increase of cortical
evoked potentials at low doses of endosulfan8. Consumption of endosulfan at low dose for
longer duration can ultimately lead to differential alterations of Monoamines (an important
class of neurotransmitters) in various regions of the rat central nervous system. An acute
neurotoxicity study in rats (gavages) showed a greater sensitivity of females compared to
males9. In a study following single oral administration of 14C-Endosulfan to male Sprague –
Dawley rats and multiple oral dosages resulted in cell death in rat and human glial and
neuronal cell cultures, α - endosulfan manifested selective neurotoxicity 10. A recent study of
investigation of the activities of Tissue plasminogen activator (t-PA) and plasminogen
activator inhibitor-1 (PAI-1) in the adult rat brain, after subchronic endosulfan treatment
resulted in systemic toxicity in mammals and induces reactive oxygen species (ROS) and
lipid peroxidation (LPO). Oxidative stress was manifested by induction of LPO as
determined by higher malondialdehyde levels. This was accompanied by elevation of Tissue
plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities. They
also found the protective measures of Vitamins E and C, well-known antioxidants, protected
the brain from these effects11. In a study it is found that endosulfan reduced ovarian size in
mice associated decrease in healthy ovarian follicles, corpora lutea and increase in atretic
follicle 12.
III. Protective measures from endosulfan toxicity:
In a recent literature, they had studied the hazardous impacts of endosulfan on olfactory
system, which play a major role in analyzing and perceiving the sense of smell, choice of
mate, and food localization in Swiss mice. The deleterious effects caused by endosulfan have
been linked to its ability in alterations of ATPase levels. Hence, there is an urgent need to
establish a counter policy by means of food regime which can check oxidative stress caused
as a result of environmental stressors. Antioxidants like resveratrol, alpha lipoic acid and
vitamin E as potential therapeutic agents in counterbalancing negative health hazards of
endosulfan on the normal functioning of brain. The result had found the inherent potential of
antioxidants against endosulfan induced neurotoxicity in the olfactory lobe of mice13.
In a study of possible protective effects of vitamin E and C against endosulfan induced
toxicity in rats showed that Vitamin C and E ameliorated the endosulfan induced oxidative
stress oxidative stress and sperm toxicity in rats.14
In an in vitro study effect of antioxidant vitamin E on rat erythrocytes against endosulfan
toxicity showed the effectiveness of Vitamin E15.
Recent studies are showing the protective effects of phytochemicals in pesticide induced
toxicity. In endosulfan induced toxicity, some studies proved that protection is possible. A
recent study revealed the protective effect of Ocimum sanctum against endosulfan induced
immunotoxicity in male Wistar rats. It is found that Ocimum sanctum has immunomodulatory
effect.16
IV. Nigella sativa
Nigella sativa is one among the indigenous medicinal plants with lot of health benefits.
Nigella sativa is an annual flowering plant, native to South West Asia .It grows to 20-30 cm
in tall , finely divided linear leaves .The flowers are delicate ,and usually coloured pale blue
and white, with 5-10 petals, the fruit is a large and inflated capsule composed of 3-7 united
follicles, each containing numerous seeds .This seed is used as spice.
Kingdom
:
Planate
Division
:
Magnoliophyta
Class
:
Magnoliopsida
Order
:
Ranunculales
Family
:
Ranunculaceae
Genus
:
Nigella
Species
:
Sativa
Seed vessels contain seeds, usually three cornered, with two sides flat and are convex, strong
agreeable aromatic odour like that of nutmegs and a spicy pungent taste. Nigella sativa has
been used for medicinal purposes for centuries both as a herb and pressed into oil in Asia,
Middle East and Africa. It has been traditionally used for a variety of conditions and
treatment related to respiratory health, stomach and intestinal health, kidney and liver
function, circulatory and immune function support, and for general wellbeing. In Islam, it is
regarded as one of the greatest forms of healing medicine available. The Islamic prophet
Muhammed once stated that the black seed can heal every disease except death. In the Unani
Subsystem of medicine, Nigella sativa is regarded as a valuable remedy for a number of
diseases. The seeds have been traditionally used in the Middle East and South East Asian
countries to treat ailments including, asthma, bronchitis, rheumatism, and related
inflammatory diseases, to increase milk production in nursing mothers, to promote digestion
and to fight parasitic infections. Its oil has been used to treat skin condition such as eczema
and boils and to treat cold symptoms. Nigella sativa Seeds are used as a carminative,
stimulant, diuretic, anthelmintic, galactogogue. It is useful in indigestion, loss of appetite,
diarrhea, amenorrhea and dysmenorrhea. To arrest vomiting, seeds are roasted and given
internally. Seeds contain, numerous ester of structurally unusual unsaturated fatty acids with
terpene alcohols (7%), trace of alkaloids are found which belong to two different types,
isochinoline alkaloids are represented by nigellimin and nigellimin -n-oxide and nigellicin. In
the essential oil, thymoquinone was identified as the main component (up to 50%). 17
In a study it is found that confirmed the gastric antisecretory and antiulcer activity of Black
seed in a well-conceived, nicely designed and perfectly executed experimental study. It
provides the most recent and intricate details of the pathogenesis of gastric ulcers and the
target of effective antiulcer drugs. They administered black seeds aqueous suspension to
experimental animals. The biochemical parameters determined the etiopathology of ulcer
disease and the mechanism of drug induced gastroprotection further strengthen the finding of
the study. 18
In another study it is found that Nigella relieves the deleterious effect of ischemia reperfusion
injury on liver. Intraperitoneally infused NS is administered before ischemia and before
reperfusion. Blood samples and liver tissues were harvested, enzymes were measured. They
concluded that, NS treatment protects the rat liver against to hepatic ischemia-reperfusion
injury. 19
According to a recent study found the role of NS and a number of its antioxidant constituents
towards azoxymethane-induced genotoxic effects and colon cancer in rats. Result showed
that, NS revealed inhibitory effects on DNA damage in the azoxymethane -treated rat.
Thymoquinone the constituent of NS inhibited maloandialdehyde (MDA) content in the liver.
They concluded that the inhibitory effects might depend on the combined competitive
inhibition of various antioxidant constituents of this plant. 20
One recent study had done the role of nigella in diabetes. It showed the multiple molecular
targets underlie the antidiabetic effect of NS seed extracts in skeletal muscle, adipocyte and
liver cell. They found that Nigella sativa seed Ethanol extract(NSE)induces an important
insulin like stimulation of glucose uptake in C2C12skeletal muscle cell and 3T3-L1
adipocytes following 18 hrs treatment. They concluded that, NS seed oil can be used as a
treatment for diabetes, for obesity and metabolic syndrome. 21
It is found that Non opioid drug Nigella sativa is effective in long term treatment of opioid
dependence. It not merely cures the opioid dependence but also cures the infections and
weakness from which majority of addicts suffer.22
References:
1. Manjula S D, Benjamin S and Laxminarayana K. Modulatory Effect of Vitamin C on
Genotoxic Effect of Endosulfan in Developing Albino Rats Iranian journal of
pharmacology and therapeutics. 2006; 5:113-116
2. Khan S and Kumari D. Analytical study of histopathological changes induced by of
endosulfan in kidney of Albino rats Asian journal of pharmaceutical and clinical
research 2012; 5(1):113-114
3. Khan S and Kumari D. Biochemical effects of Endosulfan in liver of albino rats.
International journal of pharmacy and pharmaceutical sciences. 2011; 3(4):290-291
4. Vimala Vemireddi. Immunotoxic and Oxidative Effects of Endosulfan and Permethrin
on Murine Splenocytes, in vitro. Toxicology. 2006; 5(3): 129-140
5. Victer Briz et.al, Differential estrogenic effects of the persistent organochlorine
pesticides dieldrin, endosulfan and lindane in primaryneuronal cultures. Toxicological
sciences. 2011; 4: 119-122
6. Jones D K, Hammond J I and Relyea R A. Very highly toxic effects of endosulfan
across nine species of tadpoles: lag effects and family-level sensitivity. Environmental
Toxicology and Chemistry. 2009; 28(9): 1939–1945
7. Modaresi M, Seif MR. Effects of Endosulfan on the Reproductive Parameters of Male
Rats. Journal of Reproductive Infertility. 2011; 12(2):117-122
8. Scremin O U, Chialvo D R, Lavarello S, Berra H H and Lucero M A. The
environmental pollutant endosulfan disrupts cerebral cortical function at low doses.
NeuroToxicology. 2011; 32: 31–37
9. Li D, Liu J, Li J. 2010. Genotoxic evaluation of the insecticide endosulfan based on
the induced GADD153-GFP reporter gene expression. Environ Monit Assess. 2010;
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to the exposure to endosulfan in the environment. AATEX. 2007; 5(2): 543-548
11. Zervos IA et. al, . Endosulfan-induced lipid peroxidation in rat brain and its effect on
t-PA and PAI-1: ameliorating effect of vitamins C and E. J Toxicol Sci. 2011;
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12. Azarnia L et. al, Histological examination of endosulfan effects On follicular
development of balb/c mice. Bulgarian Journal of Veterinary Medicine. 2008; 12(1):
33−41
13. Preeti Singh and Habiba Bano. A Study Showing the Ameliorative Potential of TransResveratrol, α- Lipoic Acid and Vitamin E on Endosulfan Induced Alterations in the
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stress induced due to pesticides in rat erythrocyte. Toxicology international. 2011;
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16. Bharath B.K et, al. Imuuno-modulatory effect of Ocimum sanctum against endosulfan
induced immunotoxicity. Veterinary World 2011;4 (1):25-27
17. Gargari P M, Attary V E, Gorbani M R A. Effect of dietary supplementation with
Nigella sativa Lin. on serum lipid profile, lipid peroxidation, and antioxidant defence
system in hyperlipidemic rabbits. Journal of Medicinal plants Research. 2009;
3(10):815-821
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Rafatullah S. Gastroprotective effect of an aqueous suspension of black cumin Nigella
sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi J
Gastroenterol. 2008;14(3):128–34.
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sativa relieves the deleterious effects of ischemia reperfusion injury on liver. World J
Gastroenterol. 2008; 14(33):5204-9.
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Billedo G, El-Doush I, Al-Saleh I. Role of Nigella sativa and a number of its
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