Download Title of the Topic

Title of the Topic:
INTERACTION OF CARROT (DAUCUS CAROTA) WITH PANTOPRAZOLE
AND RANITIDINE FOR ANTIULCER ACTIVITY IN ANIMALS
A) BRIEF RESUME OF THE INT ENDED WORK:
Need of study:
Peptic ulcer diseases (PUD) are the disorder of the gastrointestinal system and millions of
people suffer from this disease globally. The main causes of peptic ulcers are
hyperacidity, excessive intake of alcohol, overeating, high intake of spicy foods, food
poisoning, high intake of coffee, smoking, NSAIDs, stress, presence of helicobacter
pylori or secondary due to pathological conditions such as Zollinger-Ellison syndrome1.
Several gastric antisecretory and cytoprotective drugs are available in the market for the
treatment of PUD and none of them are free from side effects.
It is well established that diet rich in vegetables and fruits can reduce disturbances in
gastrointestinal system. Moreover, large number of populations today uses herbal
therapies and home remedies along with conventional medications. However, concurrent
use of these remedies with modern medications may cause either potentially dangerous
side effects or enhanced therapeutic efficacy2. Currently, there is very little information
available on possible interaction between herb and drug whilst the use of combined
management is progressively escalating across the world. Hence it is widely accepted that
in-depth and appropriate studies should be carried out to confirm the possible role of
combined herb- drug treatments.
The carrot (Daucus carota) belongs to the family Apiaceae. The edible part of a carrot is
a taproot. The carrot gets its characteristic and bright orange colour from β-carotene,
which is metabolised into vitamin A in humans when bile salts are present in the
intestines. Carrots are credited with many medicinal properties; they are said to cleanse
the intestines and to be diuretic. They nourish the entire system and help in the
maintenance of acid-alkaline balance in the body3. The carrot also has a reputation as a
vegetable that helps to maintain good eyesight. The carrot and its constituent, β-carotene,
has a particularly beneficial effect on the liver4. Further, carrot is known to provide relief
from diarrhea, constipation, intestinal inflammation, weakness, illness and in treating
rickets. Their protective actions are attributed to active constituents mainly A-retinol,
beta carotene, A-carotenoid, thiamin, riboflavin, niacin, pantothenic acid, folate, vitamins
A, B6, B12, C, E, K.
Eventhough, carrot is employed in traditional Indian system of medicine for variety of
ailments in gastrointestinal system, so far there is no scientific report available
confirming its ethnopharmacological claim. We also felt necessary to determine the
biological role of carrot in presence of conventional antiulcer drugs such as proton pump
inhibitor and H2 antagonist as most patients uses traditional healer ‘carrot’ with these
drugs.
Thus the present study will be undertaken to substantiate the traditional belief by
evaluating the carrot and to determine its interaction with pantoprazole (PZL) and
ranitidine (RTN) for antiulcer activity using different experimental models.
Review of Literature:
The carrot (Daucus carota subsp. Sativus) is a root vegetable, usually orange or purple,
red, white, and yellow in colour, with a crisp texture when fresh. The edible part of a
carrot is a taproot. It is a domesticated form of the wild carrot Daucus carota, native to
Europe and southwestern Asia. It has been bred for its greatly enlarged and more
palatable, less woody-textured edible taproot, but is still the same species3. It is a
biennial plant which grows a rosette of leaves in the spring and summer, while building
up the stout taproot, which stores large amounts of sugars for the plant to flower in the
second year. The flowering stem grows to about 1 metre (3 ft) tall, with an umbel of
white flowers that produce a fruit called a mericarp by botanists, which is a type of
schizocarp 5.
Carrots can be eaten in a variety of ways. The simplest way is raw as carrots are perfectly
digestible without requiring cooking. Alternatively they may be chopped and boiled, fried
or steamed, and cooked in soups and stews, as well as baby and pet foods. A well-known
dish is carrots julienne. Grated carrots are used in carrot cakes, as well as carrot
puddings, an old English dish thought to have originated in the early 1800s. The greens
are edible as a leaf vegetable, but are rarely eaten by humans, as they are mildly toxic6.
Together with onion and celery, carrots are one of the primary vegetables used in a
mirepoix to make various broths. Ethnomedically, the roots are used to treat digestive
problems, intestinal parasites, and tonsillitis or constipation. Massive overconsumption of
carrots can cause hypercarotenemia, a condition in which the skin turns orange (although
hypercarotenemia is not itself dangerous unlike overdose of vitamin A, which can cause
liver damage). Carrots are also rich in dietary fibre, antioxidants, and minerals.
B) MATERIALS AND METHODS:
Source of Data:
Data will be obtained from laboratory based studies by using albino rats of either sex
weighing between 150-200 gms, maintained at room temperature, having free access to
food (std pellet diet), tap water ad libitum. These studies will be carried out using
different experimental models such as pylorus ligation, NSAIDs, ethanol and stress
induced gastric ulcer, cysteamine inducesd duodenal ulcer as well acetic acid induced
chronic gastric ulcer.
Method of Collection of Data:
The data collected will be based on animal experimentation using rats as per the
parameters studied under each animal model, which are mentioned under the objectives
of the study.
Methods:
The rats will be grouped as follows
Group I: Control
Group II: Low dose of carrot extract (LCE)
Group III: High dose of carrot extract (HCE)
Group IV : Ranitidine (50 mg/kg p.o)7 (RTN)
Group V : Pantoprazole (20 mg/kg p.o) (PZL) 8
Group VI: Low dose of carrot extract (LCE) plus RTN
Group VII: High dose of carrot extract (HCE) plus RTN
Group VIII: Low dose of carrot extract (LCE) plus PZL
Group IX: High dose of carrot extract (HCE) plus PZL
The doses of carrot extract will be selected based on acute toxicity study carried out as
per OPPTS limit test procedure9.
Preparation of extract and preliminary phytochemical investigation: The extract will
be prepared by suitable method. Qualitative tests for chemical constituents present in the
extract will be carried out. Antiulcer evaluations will be done by following models in
experimental animals:
1. Acetic acid induced chronic gastric ulcers
The method described by Asad et al7 will be followed. Briefly, the rats will be
anaesthetized using ether followed by laporatomy, glacial acetic acid 0.05 ml will be
added onto the serosal surface of the stomach through a cylindrical mould of 6.0 mm
diameter. The acid solution will be removed after 1 min and the mould will be rinsed
with normal saline to avoid damage to surrounding tissues. The abdomen will be closed
and the animals will be treated with the drug for 10 days. On the 11th day, the animals
will be sacrificed and ulcer index and ulcer score will be determined. The tissues will also
be subjected to histopathological studies
2. Pylorus ligated rats
The Shay rat10 model with modification described by Kulkarni11 will be followed. The
pyloric end of the stomach will be ligated under light ether anaesthesia. Drug will be
administered by intraduodenal route. After 6 hr, animals will be sacrificed. The contents
of the stomach will be used for free acidity and total acidity estimations. The ulcer index
and gastric mucus content will be determined12.
3. Healing of indomethacin induced gastric ulcers, a model to study free radical
scavenging activity12
The gastric ulcers will be induced by administering indomethacin (5mg/kg. p.o.) for 5
days to the normally fed rats. The animals were then treated with the drug for 5 days
after induction of ulcer while the control group will receive only vehicle. The last dose of
indomethacin will be considered as 0th day. Rats will be sacrificed on the 0th day and 5th
day. The stomach will be removed; ulcer score and ulcer index will be determined. The
glandular portion of the stomach will be used for estimation of mucin content13, total
proteins14, antioxidant factors like super oxide dismutase activity15, total tissue sulfhydryl
groups16 and catalase activity17.
4. Ethanol induced gastric ulcers18
Albino rats will be fasted for 36 hr before administration of 90 % ethanol (1 ml/200gm).
The drug will be administered 1 hr before ethanol administration. One hour after ethanol
administration, the animals will be sacrificed, stomach will be isolated and ulcer index
will be determined.
5. Stress induced gastric ulcers19
The rats will be placed in a restraint cage and the cage will be placed at a temperature of
2° C for 3 hr. The drug will be administered 30 min prior to subjection of stress. The
animals will be sacrificed, stomach will be isolated and ulcer index was determined.
6. Cysteamine induced duodenal ulcers20
Duodenal ulcers will be induced by administering cysteamine hydrochloride (400 mg/kg
p.o) twice at an interval of 4 hr. Drug will be administered 30 min prior to each dose of
cysteamine hydrochloride. After 24 hr of the first dose of cysteamine, animals will be
sacrificed and the duodenum will be excised carefully and cut open along the
antimesentric side. The duodenal ulcer area, ulcer score and ulcer index will be
determined.
C) List of References:
1. Crawford JW. The gastrointestinal tract. In: Robbins pathologic Basis of Disease.
Cotran RS, Kumar V, Collins T (Eds), 6th Edn, Saunders, Noida India, 2000, pp
793-796.
2. Fugh-Berman A. Herb-drug interaction. The Lancet. 2000; 355:134-138.
3. http://en.wikipedia.org/wiki/Carrot.Retrieved on 29/05/09 at 9.50 am.
4. Joram Wardi, Ram Reifen, Hussein Aeed, Liliana Zadel, Yona Avni and Rafael
Bruck. Beta-Carotene Attenuates Experimentally Induced Liver Cirrhosis in Rats.
IMAJ 2001; 3:151-154.
5. http://www.northernontarioflora.ca/fruits_term_types.cfm
6. http://www.ohsu.edu/poison/documents/mildlyToxicPlants.pdf
7. Asad M, Shewade DG, Koumaravelou K, Abraham BK, Vasu S, Ramaswamy S.
Gastric anti-secretary and ant-ulcer activity of oxytocin in rats and guinea pigs.
Life Sci 2001; 70:17-24.
8. Shah PJ, Gandhi MS, Shah MB, Goswami SS, Santani D. Study of Mimusops
elengi bark in experimental gastric ulcers. : J Ethnopharmacol. 2003 ;89(2-3):30511
9. Health Effect Test Guidelines. Acute Oral Toxicity (Computer programme
OPPTS 870.1100 United State Office of Prevention. Pesticides and Toxic
Substances Environmental Protection Agency (7101). Available from URL:
http://www.epa.gov/oppts/home/guideline.htm.
10. Shay H, Komarov SA, Fele SS, Meranze D, Gruenstein H, Siplet H. A simple
method for uniform production of gastric ulceration in rat. Gastroenterology
1945; 5: 43-61.
11. Kulkarni SK. Handbook of experimental pharmacology. 3rd ed. Vallabh
Prakashan, New Delhi, India: 1999, pp148-50.
12. PrabhaT, Babu MD, Priyambada S, Agrawal VK, Goel RK. Evaluation of
Pongamia pinnata root extract on gastric ulcers and mucosal offensive and
defensive factors in rats. Indian J Exp.Biol 2003; 41(4):304 -310.
13. Majumdar B, Chaudhri SGR, Ray A, Bandyopadhyay SK. Effect of ethanol
extract of piper betle linn leaf on healing of NSAID-induced experimental ulcer–
A novel role of free radical scavenging action. Indian J Exp Biol 2003; 41(4):311315.
14. Lowry CH, Roseborough NI, Farr AL, Randall RJ. Protein measurement with
folin phenol reagent J Biol Chem 1951; 193:265-75.
15. Erich F, Elastner. Inhibition of nitrite formation from hydroxyl ammonium
chloride. A simple assay for super oxide dismutase. Anal Chem 1976; 70:616-20.
16. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophyi 1959;82:70-77.
17. Eva ML. Mechanism of pH dependent hydrogen per oxide cytotoxicity invitro.
Arch Biochem Biophy 1988; 365(2):362-72.
18. Brzozowski T, Konturek P Ch, Konturek SJ, Kwiecien S, Pajdo R, Brzozowski I,
Hahn EG.
Involvement of endogenous cholecystokinin and somatostatin in
gastroprotection induced by intra duodenal fat. J Clin Gastroenterol 1998; 27:125137.
19. Parmar NS, Jagruthi KD, A review of the current methodology for the evaluation
of gastric and duodenal anti ulcer agents. Indian J Pharmacol 1993; 25:120-135.
20. Szabo S. Animal model for human disease: Duodenal ulcer disease. Am J Pathol
1978; 73:273- 276.