Evaluation of protective effects of ipomoea batatas on doxorubicin and carbon tetra chloride induced cardiac and hepatic toxicity in rats




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EVALUATION OF PROTECTIVE EFFECTS OF IPOMOEA BATATAS ON DOXORUBICIN AND CARBON TETRA CHLORIDE INDUCED CARDIAC AND HEPATIC TOXICITY IN RATS



SYNOPOSIS FOR:

M.PHARM DISSERTATION

SUBMITTED TO

RAJIVI GANDHI UNIVERSITY OF HEALTH SCIENCES

BENGALURU, KARNATAKA

BY

Mr. BALAKRISHNA S

UNDER THE GUIDANCE OF

Mr. R. SRINATH

ASST. PROFESSOR

DEPARTMENT OF PHARMACOLOGY


PES COLLEGE OF PHARMACY,

HANUMANTHNAGAR ,

BENGALURU-560050

KARNATAKA.

2012-2014
RAJIVI GANDHI UNIVERSITY OF HEALTH SCIENCES

BENGALURU-KARNATAKA

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR

DISSERTATION

1



NAME OF THE CANDIDATE

AND ADDRESS




BALAKRISHNA S

RESIDENTIAL:NO 101, KESAREGERE (V), SUGGONDAHALLI (P), MALUR (TQ), KOLAR (DIST); KARNATAKA. PIN:563136.

PERMANENT:NO 101,KESAREGERE (V,) SUGGONDAHALLI (P), MALUR (TQ), KOLAR (DIST); KARNATAKA, PIN:563136.


2


NAME OF THE INSTITUTION

PES COLLEGE OF PHARMACY, 50 FEET ROAD, HNUMANTHANAGAR,

BENGALURU -560050



3


COURSE OF STUDY AND SUBJECT

M-PHARMA - PART-1,

PHARMACOLOGY

4



DATE OF ADMISSION

16th August 2112




5


TITLE OF THE TOPIC

EVALUATION OF THE PROTECTIVE EFFECTS OF IPOMOEA BATATUS ON DOXORUBICIN AND CARBON TETRA CHLORIDE INDUCED CARDIAC AND HEPATIC TOXICITY IN RATS.




6.0


BRIEF RESUME OF THE INTENDED WORK:

6.1 NEED FOR THE STUDY

The problem with the use of modern medicine is due to their vast and potent adverse reactions and due to their insignificant therpeutic activity and their contraindications (pregnancy, pediatrics, persistant use).



Cardio toxicity: is a condition when there is damage to the heart muscles. As a result of this, the heart may not be able to pump blood throughout the body. This may be due to the use of chemotherapy drugs, alcohol use, high cholesterol, obesity, hypertension, tobacco use, heavy metals and other medications. And use of conventional drugs like abciximab causes arrhythmia and haemorrhage, dipyidaamole causes stroke in transient ischemia attacks, Streptokinase causes hypotension, hypertensive reaction, and arrhythmia. If severe, it may lead to cardiomyopathy. Cardiomyopathy is often a result of treatments such as chemotherapeutic medications or may be caused by group of diseases or disorders that lead to damaging heart muscle(1). Cardiomyopathy may be result of viruses like HIV, amyloidosis, infection, long standing high blood pressure, chronic or long term alcohol use, diabetes, thyroid disease, thiamine and vitamin B deficiency, anthracyclins used in chemotherapy ex- doxorubicin, genetic defects etc(2).Certain other classes of drugs which may cause cardio toxicity by prolongation of QRS and QT- intervals and finally lead to conduction block like tricyclic-anti-depressants,

Anti-psychotics, anti-histamines, anti-convulsions, aextropropoxyphene, anti malarial drugs, calcium channel blockers, beta- blockers, anti arrhythmic drugs etc(3).

Doxorubicin is one of the effectively used anti-neoplastic agents commonly used for the treatment of a variety of tumours including solid and haemopoietic malignancies. Its practical therapeutic use is limited by late-onset, acute and chronic cardio toxicities, it is believed to be mediated through different mechanisms like inducing semiquinone free radical formation, ion dependent oxidative damage to biological macromolecules as well as induces the per- oxidation of unsaturated lipids within the membranes(4).

According to the current scenario cardiovascular disease (CVD) growth is

enormous in India and China. By the year 2120 India will be the largest CVD burden in the world. Currently available management for CVD disorders like arrhythmia, hypertension, angina-pectoris, congestive cardiac failure and myocardial infarction are problematic. It is therefore imperative to search alternative drugs for the treatment of cardiovascular disorders with known efficiencies and safety. A number of medicinal plants have been evaluated for CVD in India and various parts of world using toxic and safety models(5).

Hepatotoxicity: Liver, the key organ of metabolism and excretion has an immense task of detoxification of xenobiotics, environmental pollutants and chemotherapeutic agents. Hence, this organ is subjected to variety of diseases and disorders. The liver plays a vital role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Hepatotoxicity implies chemical-driven liver damage. Certain medicinal agents when taken in overdoses and sometimes even when introduced within therapeutic ranges may injure the organ. Other chemical agents used in laboratories and industries, natural chemicals can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins.

The key to predicting and preventing drug induced liver injury (DILI) is under-standing the underlying mechanisms. DILI is initiated by direct hepatotoxic effects of a drug, or a reactive metabolite (free radicals) of a drug. Parenchymal cell injury induces activation of innate and/or adaptive immune cells, which, in turn, produce proinflammatory and tissue hepatotoxic mediators, and/or mount immune reactions against drug-associated antigens. Understanding the molecular and cellular elements associ-ated with these pathways can help identify risk factors and may ultimately facilitate the development of strategies to predict and prevent DILI.

More than 900 drugs have been implicated in causing liver injury and it is the most common reason for a drug to be withdrawn from the market.

Drug-induced liver injury (DILI) is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. According to the United States Acute Liver Failure Study Group, DILI accounts for more than 50% of acute liver failure, including hepatotoxicity caused by overdose of acetaminophen (APAP, 39%) and idiosyncratic liver injury triggered by other drugs (13%). Because of the significant patient morbidity and mortality associated with DILI, the U.S. Food and Drug Administration (FDA) has removed sev-eral drugs from the market, including bromfenac, ebrotidine, and troglitazone. Other hepatotoxic drugs, such as risperi-done, trovafloxacin, and nefazodone, have been assigned “ black box ” warnings. DILI is the most common cause for the withdrawal of drugs from the pharmaceutical market(6).

The Curative properties of medicinal plants are mainly due to the presence of various complex chemical substances of different composition which occur as secondary metabolites. They are grouped as alkaloids, glycosides, flavonoids, saponins, tannins, carbohydrates & essential oils. Plant based constituents can be derived from any part of the plant like bark, leaves, flowers, roots, fruits, seeds etc. these herbs help the liver to eliminate toxins, drug induced injury and from microbial infections(7).

Howerer,there are several plant derived preparations in the ancient text of a ayrveda and siddha for the treatment of such disorders. With continuation of new drug discovery,plants and their preparation scentifically proven their clinical applicability. In this view the present study has been selected for evaluation of Ipomoea batatas for its cardio and hepato protective activity.



6.2 REVIEW OF LITERATURE:

Ipomoea batatas (sweet potato) is a dicotyledonous plant that belongs to the family Convolvulaceae. The leaf extracts of Ipomoea batatas (sweet potato) have shown the presence of total Flavonoids, total phenolics, reducing activity and the ability to scavenge free radicals. Ipomoea batatus contained highest level of total phenolics and scavenging activity with the IC50 value of
372.4μg/ml and thus a potential source for antioxidants. Besides, all the different varieties of Ipomoea batatas leaves are found to be stronger scavenger compared to vitamin C. The reducing power of Ipomoea batatus leaf extracts increased with concentration with higher level of reducing power. Despite differences in their storage roots, all the Ipomoea batatas leaves varieties contained antioxidants that are beneficial to the human body(8).

The action of Flavonoids can be divided into two different mechanisms,

I.e., 1: Scavenging process.

2: Chelating process(8).

Plant profile(9)

Kingdom : plantae - plants

Subkingdom : Tracheobionta – vascular plants

Super division: Spermatophyte – seed plants

Division : Sagnoliophyta – flowering plants

Class : Magnoliopsida – Dicotyledons

Sub class : Asteridae

Order : Solanales

Family : Convolvulaceae

Genus : Ipomoea L. – morning glory family

Species : I. batatas (L.) LAM – sweet potato

Synonyms (10): Tamil : Sakkara valli Kilangu.

Kannada : Genasu.

Hindi : Shakarkand / Ratalu.

Telugu : Chilakada dumpa.

Marathi : Ratala.

Bengali : Mishti Alu.

Malayalam: Mathura Kizhangu.

Scientific names (11) batatas edulis Choisy (Kamote (all dialects )

Convolvulus batatas Linn (Lapin (if.)

Convolvulus edulis Choisy (Pangg-bagun (Sul.)

Ipomoea batatas (L.) (Sweet potato (Engl.),

( Yam (Engl.),

Geographical distribution: The plant is commonly seen growing in all parts of India, Asian and some other European and American countries(9).

Chemical constituents of leaf: Sweetpotato roots and tops possess a variety of chemical compounds relevant to human health. About 80 to 90 % of sweetpotato dry matter is made up of carbohydrates, consisting mainly of starch (60-70%) and sugars with lesser amounts of pectins, hemicelluloses and cellulose. Sweet-potato also contains protein (0.46%-2.93%), dietary fiber (0.49%-4.71%), lipid (0.06%-0.48%) and ash (0.31%-1.06%).

It contains essential mineral nutrients such as Ca(117mg), (0.56mg),vit E(0.56mg), Fe(1.8mg)/100mg, S, Cu, Zn, P, Mg, Na, K, Mn, Al and B.Sweetpotato is also an important source of vitamin A, thiamin, riboflavin, niacin, ascorbic acid,β-carotene and many other functional compounds.

Sweetpotato leaves are an excellent source flavonoids with antioxidative poly-phenols, with 6 polyphenolic compounds ,15 anthocyanins and phenolic acids such as caffeic, monocaffeoylquinic (chloro­genic), dicaffeoylquinic and tricaffeoylquinic acids, and are superior in this regard to other commercial vegetables(12).
The another major constituent flavonoids is proanthocyaniins and two or more flavan-3-ol such as catechin, epicatechin or gallocatechin. Catechin contains 2 benzene rings to be the powerful scavenger(8).

USES OF IPOMOEA BATATAS(12):

1 : The young leaves and shoots are sometimes eaten as greens.

2 : All parts of the plant are used for animal fodder.

3 : Industrial alcolol production.

4: Sweetpotato leaves used as a vegetable, a tea, in noodles, in breads, in confec­tioneries and as a nutritional supplement.

Reported activities of Ipomoea batatas:

1: Makoto yoshimoto and shoji yahara evaluated the anti-mutagenic activity of the caffeoylquinic acid derivatives in Ipomoea batatas leaf(13).

2: poly phenolics have attracted special attention due to their use in oxidative stress which may cause cancer, aging.

3: Mukesh Nandave, SK Ojha and DS Arya reported that flavonoids show anti-thrombotic, anti-ischemic, anti-arrythmic and cardioprotective activity by free radical scavenging mechanism(14).

4: The leaf extracts also shows anti-bacterial activity(8), ultraviolet protection effect, anti-inflammation and promotion in bowel movement.

Folkloric use:
-Crushed leaves applied to boils and acne. 
-Boiled roots used for diarrhea.

Other reported activities (12):
• Dengue: 
Like gatas-gatas (Euphorbia hirta), there have been anecdotal reports of the use of Ipomoea batatas in dengue, with improvement in platelet counts being attributed to decoctions of kamote tops.

Preparation: leaves are boiled in water for 5 minutes to extract the juice.


• Diabetes : 
(A) Despite its "sweet" name, it may be beneficial for diabetes as some studies suggest it may stabilize blood sugars & lower insulin resistance.

(B) Study showed the flavone extracted from IB leaf could control blood sugar and modulate the metabolism of glucose and blood lipid, and decrease outputs of lipid peroxidation and scavenge the free radicals in NIDDM.


• Hematologic: 
Hemostatic mixture of ipomoea balatas leaves, methods of preparation and use thereof — a Jinshuye styptic plant preparation, an invention made from the extracts of leaf and stems of Ipomoea batatas has qi and spleen invigorating effects, cooling the blood and stopping bleeding. Such a composition has the potential of use for ITP (idiopathic thrombocytopenic purpura), radiotherapy- and chemotherapy-induced thrombocytopenia. 
• Antioxidant: 
(A) Study results suggest the total phenolic content was positively correlated with radical scavenging activities of the sweet potato leaves.

(B) Purple Sweet Potato anthocyanins have antioxidative activity in in-vivo andin-vitro.


• Diabetes:

(A) Antidiabetic activity of white skinned sweet potato (Ipomoea batatas L.) in obese Zucker fatty rats: Results suggest the white skinned sweet potato has antidiabetic activity and and improves glucose and lipid metabolism by reducing insulin resistance. 

(B) Study to isolate the antidiabetic component of white-skinned sweet potato suggested the active component to be an acidic glycoprotein because it contained a protein and sugar and adsorbed onto the QA column at pH 7.0.s


• Caiapo: Study confirmed the beneficial effects of Caiapo (a neutraceutical) on plasma glucose with a decrease in Hb A1c, as well as cholesterol in type 2diabetes.

• Flavonoids: Leaf extract study isolated five news compounds: tiliroside, astragalin, rhamnocitrin, rhamnetin and kaempferol.


• Chitinases: 
Study identified new chitinolytic enzymes in sweet potato leaves. Chitinases catalyze the hydrolysis of chitin, the main structural component of fungal walls and arthropod integuments. Studies suggest it has other functions and has been proposed to play a role in the defense against pathogens. Chitinases are also useful in the production of biomedical and biotech products; used in the production of chitooligosaccharides, glucosamines and GlcNAc. Other applications are found in mosquito control and patho-genic plant fungi control.
• Antiproliferative: Study demonstrated that the phytochemicals in sweet potato may have significant antioxidant and anticancer activities. The antioxidant activity was directly related to the total amount of phenolics and flavonoids in the extracts. The additive roles of phytochemicals may contribute to its ability in inhibiting tumor cell proliferation in-vitro.
• Antidiabetic / Adiponectin / Natural Insulin Sensitizer: Study confirms the beneficial effects of Caiapo on glucose and HbA1c in T2DM. The improvement in insulin sensitivity was accompanied by increased levels of adiponectin and a decrease in fibronogen.

• Effects on Glucose and LDL in Type2 Diabetes /Antiproliferative: Pilot study showed a beneficial effect of high-dose caiapo on plasma glucose and LDL cholesterol levels in patients with type 2 diabetes The effect was attributed. 


• Antiulcer: Study in cold stress and aspirin-induced gastric ulcers in Wistar rats showed Ipomoea batatas tubers possess gastroprotective activity as shown by inhibition of mean ulcer score and ulcer index and a marked increase in GSH, SOD, CAT, GPx, and GR levels and reduction in lipid peroxidation.

• Antiproliferative / Antioxidant: Study examined the antioxidant and antiproliferative activities of different extracts of sweet potato. In the DPPH staining, the ethanol extract of vein had the highest radical-scavenging


activity. Among the extracts the ethanol extract showed the highest amount of total phenolic and flavonoid compounds. Water extract of the vein showed the highest antiproliferative activity with an EC50 of 449.6 ± 27.73 ug/mL(8).
• Comparative Antioxidant Properties / Natural Yellow Dye: Study showed the carotenoids extraction process retained most of the antioxidant capacity from the leaves. It is also a potential source of natural yellow dye with antioxidant property that can be beneficial to human health, as an alternative to the artificial colouring dye currently used in the market.
• Anthocyanins / Antitumor Effect: Study showed Ipomoea batatas Poir Cv anthocyanins could have an inhibitory effect on transplantation tumor of mice with no toxicity and no mutation(8).

• Wound Healing: In an incision wound model, high tensile strength of the wounded skin was noted in animals treated with peel extract gels and the peel bandage when compared to controls. There was also significant wound closure by the 4th day, a significant increase in hydroxyproline and ascorbic acid and decrease in malondialdehyde content. The wound healing activity was attributed to possible underlying antioxidant mechanism.


• Hypoglycemic Effect: Study in STZ-induced hyperglycemic rats fed oral doses of extracts showed significant dose-related reductions in FBG. Phytochemical analysis of the extract showed alkaloids, flavonoids, tannins, saponins, anthraquinones and reducing sugars and some vitamins.

• Thyroid-Gonadal Axis Effect: Study investigated the effect of a leaf extract on the thyroid gonadal axis of male rats. Results showed follicles hypertrophy and hyperplasia and reduction of colloid in the follicular lumen. Testes morphology showed oligospermia, asthenospermia and abnormal sperm morphology. Results suggest a male contraceptive property of the plant extract, the mechanism possibly as both a direct effect on the gonals of indirectly via the hypothalamo-hypophyseal axis.




6.3: OBJECTIVE OF THE STUDY:

1.To study the cardio protective effects of Ipomoea batatus (sweet potato) in doxorubicin induced cardio toxicity in rats.

2.To study the cardio protective effects of Ipomoea batatus (sweet potato) in carbon tetra chloride induced hepatotoxcity in rats.

Steps involved

A.Collection and authentification of Ipomoea batatus.

B.extraction of plant material by ethanol using soxhlet apparatus.

C.To establish the pharmacological profile of prepared extracts for its cardio protective effects induced by doxorubicin, followed by carbon tetra chloride induced hepatotoxcity.



7: MATERIALS AND METHODS:

7.1 Source of data: Whole work is planned to generate data from laboratory i.e., experiments on animals are performed as described in references. The rats will be used for this purpose. Experimental studies in journals and in text books available with college and various institutions. It is also planned to use the available literature for interpreting the data.

PESCP library, Bengaluru.

RGUHS digital library (Helinet), Bengaluru.

Web site: www.sciencedirect.com

www.pubmed.com

www.google.com

www.ijp-online.com

www.bjp-online.com



7.2 Materials.

Plant : Ipomoea batatas

Parts used : leaves

  • Chemicals and drugs: Doxorubicin, Carbon tetra chloride, silymarin and ethanolic extract of Ipomoea batatus,

  • Animals : Albino wiatar rats.

Male wistar rats weighing 150-200 grams will be used .The animals will be maintained under controlled condition of temperature (23 ± 2oC), humidity (50 ±5%) and 12 hour light and dark cycles. The animals are randomized into experimental and control group and housed in sanitized polypropylene cage containing sterile paddy husk as bedding. They will also have free access to standard pellet as diet and water.

  • Instruments : Microscope, centrifuge, bar.

7.3. METHODS OF COLLECTION OF DATA (including sampling procedure if any): The whole study is divided into following phases;

7.3.(a) COLLECTION OF DATA:

The plant material will be procured from the registered suppliers and authentification of plant will be done in the regional research institute.



7.3.(b) PREPARATION OF THE EXTRACT:

Naturally occurring Ipomoea batatas herbs will be collected and extracted with ethanol and these extracts will be used for this study(15).

Acute oral toxicity studies of Ipomoea batatas plant leaves will be done according to The Organization of Economic Co-operation and Development (OECD) guidelines No:423 and low and high dose will be selected for treatment(16).

7.4. For the determination of cardio-protective and hepato-protective activity the following animal model experiments are to be performed.

7.4.A. Model-1: Doxorubicin induced cardiotoxicity(17).

The animals will be randomly divided into 5 groups with 6 animals each.



  • Group I- Control receives only vehicle orally for 10 consecutive days.

  • Group II- Receives extracts p.o. at maximum dose for 10 consecutive days.

  • Group III- Receives doxorubicin 15mg/kg i.p. once on 7th day. Before 7th day it receives only vehicle orally.

  • Group IV- Receives extract low dose, p.o. for 10 days and once on 7th day receives doxorubicin 15mg/kg i.p.

  • Group V- Receives extract high dose p.o. for 10 days and doxorubicin once on 7th day in the dose of 15mg/kg i.p.




Groups

Treatment

Dose & route of adminitration

Treatment shedule

No.of animals

Group 1

Vehicle


p.o

1ST to 10TH DAY

6

Group 2

EEIB*

High dose , p.o

1ST to 10TH DAY

6

Group 3

Doxorubicin (single dose)

15 mg/kg

I.p.


ON 7TH DAY


6

Group 4

Doxorubicin + EEIB

15 mg/kg +

low dose ,p.o



ON 7TH DAY +

1ST to 10TH



6

Group 5

Doxorubicin + EEIB

15 mg/kg +

high dose , p.o



ON 7TH DAY +

1ST to 10TH



6

*EEIB: Ethanolic extract of Ipomoea botatas.

The dose of the extract will be selected after performing acute toxicity studies.


PARAMETERS TO BE EVALUATED


  1. ECG

  2. Cardiac tissue analysis(17).

    1. Protein content.

    2. Lipid pero-xidation.

    3. Superoxide dismutase (SOD).

3) Serum biochemical analysis(18).

a) Creatinine phosphokinase (CPK).

b) Lactate dehydrogenase (LDH) activity.

c) Creatinine kinase-MB.

4) Histopathology.



Biochemical analysis:-

At the end of the study, 24 h after the last treatment i.e. on 11th day, rats will be anaesthetized with thiopentone (35mg/kg) i.p. and ECG will be recorded. Blood samples will be collected by retro orbital puncture in serum separating tubes. The blood will be centrifuged to separate serum. The sera will be stored in ice-cold conditions. This will be utilized for biochemical analysis. Estimation of serum Creatinine phosphokinase and lactate dehydrogenase (LDH) activities will be determined according to standard methods using diagnostic kits.



Histopathological examination:-
The abdomen of each rat will be opened and heart will be dissected out and washed in ice- cold isotonic saline solution and will be bloated between two filter papers. The hearts will be fixed in 10% formalin for Histopathological examination. Two hearts from each group are taken. The remaining hearts from each group will be homogenized in ice-cold 0.1M potassium phosphate buffer (pH- 7.4) and it will be analyzed for subsequent analysis.

Cardiac tissue analysis.

parameters:

1. Determination of protein content :

The protein content of cardiac tissue homogenates will be determined by the Lowry protein assay using bovine serum albumin as standard.

2. Lipid per-oxidation, catalase activity, superoxide dismutase (SOD) activity.


7.4. B. Model 2: carbon tetra chloride induced Hepatotoxicity(19).

Rats were divided into five groups, each group consisting of six animals.

•Group I: Controls received the vehicle of normal saline (2 ml/kg, p.o.).

•Group II: Received CCl4 (2 ml/kg, s.c.) at every 72 h for 10 days [5].

•Group III: Received Silymarin 50 mg/kg p.o. for 10 days and simultaneously administered CCl4 (2 ml/kg, s.c.) at every 72 h.

•Group IV: Received ethanolic extract (low dose) of Ipomoea batatas p.o. for 10 days and simultaneously administered CCl4 (2 ml/kg, s.c.) at every 72 h.

•Group V: Received ethanolic extract (high dose) of Ipomoea batatas p.o. for 10 days and simultaneously administered CCl4 (2 ml/kg, s.c.) at every 72 h.

Groups


Treatment

Dose and route of administration

Treatment for 10 days

No: of animals

Group 1

Control:

normal saline


2ml/kg p.o




10 days

6

Group 2

Treatment:CCL4

2ml/kg s.c

CCL4 at every 72h

6

Group 3

Silymarin

50mg/kg p.o,

CCL4 s.c



10days and CCL4 at every 72h

6

Group 4

*EEIB (LOW DOSE) +

CCL4



p.o

10days and CCL4 at every 72h

6

Group 5

EEIB (HIGH DOSE) +

CCL4



p.o

10days and CCL4 at every 72h

6

*EEIB: ETHANOLIC EXTRACT OF IPOMOEA BATATAS



PARAMETERS TO BE EVALUATED
1.ASSESSEMENT OF LIVER FUNCTIONS

A.BIO-CHEMICAL PARAMETERS (20, 21).



  • Aspartate amino transferase (AST).

  • Alanine amino transferase (ALT).

  • Total bilirubin and total protein.

2. TISSUE ANALYSIS.



  • PROTEIN CONTENT

  • LIPID PER-OXIDATION

  • SUPEROXIDE DISMUTASE

3. HISTOPATHOLOGICAL STUDIES (22).

STATISTICAL ANALYSIS: - All the values will be expressed as mean± SEM. The data will be analyzed by using one way ANOVA followed by suitable post-hoc test. Statistical significance will be set at p< 0.05.13
DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS /ANIMALS? IF SO PLEASE DESCRIBED BRIEFLY.

Yes, the above study requires investigation to be done on the Albino Wistar rats for the determination of Cardio protective and hepatoprotective activity.


7.5. HAS ANIMAL ETHICAL COMMITTEE CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE?

Yes, ethical clearance has been obtained [copy of IAEC clearance has been attached.



BIBILOGRAPHY


  1. Goodman & Gilman's. The Pharmacological Basis of Therapeutics. 10th Edition ed. Hardman JG, Limbird LE, AG. G, editors. New York: McGraw-Hill2001.




  1. Sabina EP, M. R. Cardiotoxicity and cardiomyopathy. 2011 dec 10; Availablefrom: http://www.chemocare.com/managing/cardiotoxicity_and_cardiomyopathy.asp.



  1. Chemocardiac 2011 dec 10 ; Available from: http://www.uic.edu/classes/pmpr/pmpr652/Final/bressler/chemocardiac.html.




  1. Nivethetha M, Jayasri J, Brindha P. Effects of Muntingia calabura L. on isoproterenol-induced myocardial infarction. Singapore medical journal. 2009;50(3):300.




  1. Cardiovascular health . 2011 dec 02 ; Available from: http://en.wikipedia.org/wiki/Cardiotoxicity.




  1. Michael P. Holt, Ju. C. Mechanisms of Drug-Induced Liver Injury. The AAPS Journal 2006;8(1).




  1. Arshed ID, Vikas S, Saxena RC, SK. B. HEPATOPROTECTIVE ACTIVITY OF CITRULLUS COLOCYNTHIS LINN. Inventi:ep. 2011;2(2):331.




  1. Seow-Mun Hue, Amru Nasrulhaq Boyce, Somasundram. C. Antioxidant activity, phenolic and flavonoid contents in the leaves of different varieties sweet potato. AJCS. 2012;6(3):375-80.




  1. base pd. natural resources conservation service. usda.

10. Available from: http://google.com.


11. PHILIPPINE MEDICINAL PLANTS [database on the Internet]. Available from: http://www.stuartxchange.org/Kamote.html




  1. Islam. S. Medicinal and Nutritional Qualities of Sweetpotato Tops and Leaves. University of Arkansas at Pine Bluf. [Plant Science].

13. Makoto Yoshimoto, Shoji Yahara, Shigenori Okno, Md. Shahidul Islam, Koji Ishiguro, Yamakawa. O. Antimutagenicity of Mono-, Di-, and

Tricaffeoylquinic Acid Derivatives isolated from sweet potato.Biosci Biotechnoi Biochem. 2002;66(11):2336-41.
14. Mukesh Nandave, S K Ojha, Arya. Protective role of flavonoids in cardiovascular diseases. [review article].
15. Fenglin LI, Qingwang Li, Dawei Gao, Peng. Y. The Optimal Extraction Parameters and Anti-Diabetic Activity of Flavonoids from Ipomoea Batatas Leaf. AJTCAM. 2009;6(2):195-202.
16. toxicity. AO. 423 Acute Oral toxicity. Acute Toxic Class Method. 2001 17th December 2001.
17. Elberry AA, Abdel-Naim AB, Abdel-Sattar EA, Nagy AA, Mosli HA, Mohamadin AM ea. Cranberry (Vaccinium macrocarpon) protects against doxorubicin-induced cardiotoxicity in rats. Food Chem Toxicol. 2010;48:1178–84.

18. Momin FN, Kalai BR, Shikalgar TS, Naikwade NS. Cardioprotective effect of methanolic extract of Ixora coccinea Linn. leaves on doxorubicin-induced cardiac toxicity in rats. Indian J Pharmacol. 2012 Mar;44(2):178-83.


19. Muthu Gounder PALANIVEL, Balasubramanian RAJKAPOOR*, Raju SENTHIL KUMAR, John Wilking EINSTEIN, Ekambaram Prem KUMAR, Mani RUPESHKUMAR ea. Hepatoprotective and Antioxidant Effect of Pisonia aculeataL. against CCl4- Induced Hepatic Damage in Rats. Sci Pharm. 2008;76:203-15.
20. Yang J, Xu MQ, Yan LN, Chen XB, Liu J. Zinc finger protein A20 protects rats against chronic liver allograft dysfunction. World J Gastroenterol. [Research Support, Non-U.S. Gov't]. 2012 Jul 21;18(27):3537-50.
21. Gregorczyk J, Kosmider K, Wieckowski B, Wesoowska T. [Investigations on the extent of liver lesions in rats by experimental inhalation poisoning with carbon disulfide. I. Analysis of biochemical changes in the blood serum (author's transl)]. Int Arch Arbeitsmed. 1975;34(1):65-80.
22. Jadhav VB, Thakare VN, Suralkar AA, Deshpande AD, Naik SR. Hepatoprotective activity of Luffa acutangula against CCl4 and rifampicin induced liver toxicity in rats: a biochemical and histopathological evaluation. Indian J Exp Biol. 2010 Aug;48(8):822-9.


08.

NAME OF THE CANDIDATE

BALA KRISHNA S


09.

SIGNATURE OF THE CANDIDATE

(BALA KRISHNA S)



10.

REMARKS OF THE GUIDE

FORWARDED FOR APPROVAL






10.1


NAME AND DESIGNATION OF THE GUIDE



Mr. R.SRINATH,

ASSISTANT PROFESSOR,

DEPARTMENT OF PHARMACOLOGY

PES COLLEGE OF PHARMACY,

BENGALURU-50.



10.2


SIGNATURE






10.3


CO-GUIDE (IF ANY)



Not Applicable


10.4


SIGNATURE

.

Not Applicable

11.



HEAD OF THE DEPARTMENT


Mr. SHIVALINGE GOWDA.K.P,

HOD & ASST.PROFESSOR,

DEPT.OF PHARMACOLOGY

P.E.S. COLLEGE OF PHARMACY





11.1


SIGNATURE




12


REMARKS OF THE PRINCIPAL






12.1


SIGNATURE


Prof. Dr. S.MOHAN,

PRINICIPAL AND DIRECTOR

P.E.S. COLLEGE OF PHARMACY

BENGALURU-560050









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