“EVALUATION OF ANTIDIABETIC ACTIVITY OF HELICTERES
“EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF ACE- INHIBITORS / ANGIOTENSIN II TYPE I RECEPTOR BLOCKERS AGAINST PARACETAMOL INDUCED LIVER DAMAGE IN RATS”
Synopsis for registration of M.Pharm Dissertation
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
[pic]
In partial fulfillment
Of the requirement for the Degree of
MASTER OF PHARMACY IN PHARMACOLOGY
Under the Guidance of
Dr.D.SHESHADRI SHEKAR
M.Pharm., Ph.D.
BY
P.Madhavi Latha
I M. PHARM.
DEPARTMENT OF PHARMACOLOGY
SRI K.V.COLLEGE OF PHARMACY, CHICBALLAPUR-562101
(2013-14)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
| | | |
|1. |Name of the candidate and address |P.Madhavi Latha |
| | |D/O late P.C.Dasari |
| | |C/o M. Vengal Reddy |
| | |26/349-B, M.S Nagar, Nandyal, |
| | |Kurnool (Dist), Andhra pradesh. |
| | | |
|2. |Name of the Institution |SRI K.V.COLLEGE OF PHARMACY, |
| | |M.G.ROAD, CHICKBALLAPUR, |
| | |KARNATAKA-562101 |
| |Course of study and subject | |
|3. | |MASTER OF PHARMACY IN PHARMACOLOGY |
| |Date of the admission | |
|4. | |13/08/2012 |
| |Title of the topic: |
|5. |“EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF ACE- INHIBITORS / ANGIOTENSIN II TYPE I RECEPTOR BLOCKERS AGAINST PARACETAMOL |
| |INDUCED LIVER DAMAGE IN RATS” |
| | |
|6. |6.1. NEED FOR THE STUDY: |
| | |
| |Liver disease has become one of the major causes of morbidity and mortality all over the world. About 20,000 deaths found every|
| |year due to liver disorders. The liver transforms and excretes many drugs and toxins. These substances are frequently converted|
| |to inactive form by reactions that occur in the hepatocytes1, 2. The liver damage may involve mainly the hepatic parenchymal |
| |cells, cells of the excretory tree or both. In the case of some hepatotoxic agents, vascular structures are the primary focus |
| |of injury, acute hepatic injury may be translated into chronic liver diseases, expressed as cirrhosis or even as carcinoma . |
| |Liver damage is associated with cellular necrosis, increase in tissue lipid peroxidation and depletion in the tissue |
| |glutathione (GSH) levels. In addition serum levels of many biochemical markers like Aspartate Transaminase (AST), Alanine |
| |Transaminase (ALT), triglycerides, cholesterol, bilirubin & alkaline phosphatase (ALP) are elevated3. The liver may be |
| |considered as the most important organ in drug toxicity for two reasons: on the one hand it is functionally interposed between |
| |the site of absorption and the systemic circulation and is a major site of metabolism and elimination of foreign substances; |
| |but on the other hand these features also render it a preferred target for drug toxicity4. Many times liver is damaged due to |
| |chemicals, alcohol consumption and because of few drugs which are normally used for therapy5. |
| |Drug-induced liver injury (DILI) therefore poses a major clinical problem. Overdosage of paracetamol (PCM) leads to the |
| |saturation of conjugation pathway leading to GSH depletion and increase in the formation of toxic reactive metabolites6, 7 |
| |which increase the level of hepatotoxicity. Intrinsic hepatotoxicity following acetaminophen and alcohol overdose accounts for |
| |the majority of cases of drug-induced acute liver failure. In contrast, hepatotoxicity associated with most other drugs is |
| |idiosyncratic, which implies by definition that DILI develops in only a small proportion of subjects exposed to a drug in |
| |therapeutic doses, and the risk of acute liver failure associated with idiosyncratic hepatotoxins is usually less than 1 per |
| |10,000 exposed patients. DILI also represents a major challenge for industry and regulatory authorities, it is a leading cause |
| |for termination of further substance development in preclinical and clinical phases, and it is also the most common single |
| |adverse drug reaction leading to refusal of market approval4. |
| |Hepatoprotective agents are those compounds, which mitigate the liver injury caused by hepatotoxic agents. The compounds which |
| |have been reported to possess the hepatoprotective activity are Glycine8, Tocopherol9, Rimonabant10, Methionine11, |
| |N-acetylcysteine12 , Cystathionine13, ACE-Inhibitors14 and Angiotensin II type I receptor blockers15. As such no information is|
| |available regarding the hepatoprotective activity of ACE- Inhibitors and Angiotensin II type I receptor blockers against |
| |Paracetamol induced liver damage in rats. Hence present study has been undertaken to find out the hepatoprotective activity of|
| |Ace- inhibitors and Angiotensin II type I receptor blockers against Paracetamol induced liver damage in rats. |
| | |
| |6.2. REVIEW OF LITERATURE: |
| |ACE Inhibitor drugs inhibit competitively the activity of ACE (also termed kininase II) to prevent formation of the active |
| |octapeptide, angiotensin II, from the inactive decapeptide, angiotensin I. This occurs in blood and tissues including kidney, |
| |heart, blood vessels, adrenal gland and brain. Angiotensin II is a potent vasoconstrictor, promotes aldosterone release, |
| |facilities sympathetic activity and has other potentially harmful effects on the cardiovascular system. Reduction in blood |
| |pressure secondary to vasodilatation following ACE inhibition is greatest when the renin-angiotensin system is stimulated (e.g.|
| |following diuretic therapy or in renal artery stenosis) but ACE inhibitors also lower blood pressure when there is normal or |
| |low activity of the renin-angiotensin system. Recent evidences showed that ACE Inhibitors like Captopril and Enalapril showing |
| |hepatoprotective activity against paraquat toxicity.14 |
| |Angiotensin II type I receptor blockers, act competitively antagonise angiotensin II receptor type1 (AT1) receptor, reducing |
| |the end organ responses to angiotensin II. Administration of this results in a decrease in total peripheral resistance |
| |(afterload) and cardiac venous return (preload) All of the physiological effects of angiotensin II, including stimulation of |
| |release of aldosterone, are antagonized in the presence of Angiotensin II type I receptor blockers. Reduction in blood pressure|
| |occurs independently of the status of the renin-angiotensin system. A growing number of studies have suggested that rennin |
| |angiotensin system (RAS), an important factor in regulating blood pressure and body fluid homeostasis, is also involved in |
| |hepatic fibriogenesis. Patient with chronic liver disease, showed an increase in plasma activity.Experimental studies have |
| |revealed that blockade of RAS with ACE inhibitors or the AT1 receptor blockers can significantly slow down the progression of |
| |fibrotic disease.15 |
| |6.3. OBJECTIVE OF STUDY: |
| |The objective of the proposed study is to evaluate hepatoprotective activity of Ace- inhibitors and Angiotensin II type I |
| |receptor blockers against Paracetamol induced liver damage in rats. |
| |MATERIALS AND METHODS : |
| |7.1. SOURCE OF DATA: |
| |Whole work is planned to generate data from laboratory studies i.e. experiments are performed as described in references. |
| |Experimental studies in journals and in text books available with college and other libraries. Literature is searched from |
| |various web sites in the internet. |
| | |
| |7.2. METHOD OF COLLECTION OF DATA: |
| |The data collected will be based on animal experimentation as per the parameters studied, which are mentioned in objective of |
| |the study. |
| | |
| |EXPERIMENTAL DESIGN: |
| |REQURIEMENTS: |
| |Animal : Rat [Albino Wistar strain] |
| |Sex : Male and Female. |
| |Body weight : 150-220 g |
| |Chemicals : Ace- inhibitors , Angiotensin II type I receptor blockers, PCM, & Biomarkers kits (MERCK). |
| | |
| |METHODOLOGY : |
| |The rats were divided into the following groups each containing 6 rats and the study was being carrying out with three models |
| |as follows |
| |PARACETAMOL INDUCED 16 |
| |Group 1: Vehicle control |
| |Group 2: Curative studies will be performed by administration of PCM (2g PCM/kg BW p.o) for first three days followed by |
| |therapeutic dose (TD) of ACE Inhibitor alone for next 6days. |
| |Group 3: Curative studies will be performed by administration of PCM (2g PCM/kg BW p.o) for first three days followed by the |
| |(TD) Angiotensin II type I receptor blockers of alone for next 6days. |
| |Group 4: Prophylactic studies will be carried out by the simultaneous administration of TD of ACE Inhibitor followed by PCM (2g|
| |PCM/kg BW p.o) for 10days. |
| |Group 5: Prophylactic studies will be carried out by the simultaneous administration of TD Angiotensin II type I receptor |
| |blockersof followed by PCM (2g PCM/kg BW p.o) for 10days. |
| |Finally, treated rats receive Thiopentone sodium (40mg/kg b.w.) on next day of the last dose treated in all groups and the |
| |study was terminating after 24hr post administration. All the animals were sacrifice, for blood analysis and histopathological |
| |studies. |
| |PARAMETERS TO BE EVALUATED: |
| |1. Liver will be isolated and weighed. |
| |2. Blood samples will be collected and estimated ALT, AST, ALP, Albumin, total serum bilirubin and total proteins etc. |
| |3. Liver will be isolated and processed for the estimation of anti-oxidant enzymes like catalase (CAT), Glutathione (GSH), |
| |superoxide dismutase (SOD), Glutathione peroxidase (GPX) and lipid peroxidation (LPO) etc. |
| |4. Liver will be subjected for histopathological studies. |
| | |
| |7.3 STATISTICAL ANALYSIS: |
| | |
| |The statistical significance of the results will be analyzed by multiple analysis of variance (ANOVA). p ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related searches
- sample of evaluation of employees
- importance of physical activity pdf
- benefits of physical activity pdf
- benefits of physical activity worksheet
- benefits of physical activity handout
- point of view activity pdf
- stages of change activity pdf
- real life examples of routine activity theory
- types of physical activity list
- importance of physical activity for children
- bill of rights activity worksheet
- principal activity of your business