HEPATOPROTECTIVE ACTIVITY OF GLIMEPIRIDE BY INDUCING CCL4 HEPATOTOXICITY

 

{ DOWNLOAD AS PDF }

ABOUT AUTHORS
C.V.H.Hemavathy*, B. Raj kumar, R. Kiran kumar, G. Hema latha

Department of Pharmacy,
Kottam Institute of Pharmacy,
Erravally X Roads, Mahaboob Nagar
*hemarayudu19@gmail.com

ABSTRACT
Hepatoprotective activity of  by inducing ccl4 hepatotoxicity. To study the hepatoprotective activity of against CCL4 induced hepatotoxcity. To evaluate the mechanism of hepatoprotection in terms of Liver antioxidant mechanism, Histopathological study. The animals were divided into Four groups of  three animals each. Except the normal group all the other groups received ccl4 in at a dose of 0.1 ml/kg by intraperitoneally for 14 days. Normal groups received plain tween 80 orally.  On the 14th day all the rats from all the groups were sacrificed, blood was collected from each animal for serum analysis  and their livers were stored  under freezing conditions for the estimation of endogenous anti oxidants and one sample from each group was stored in 10% formalin for histopathological studies.  In bio-chemical studies- Serum analytical methods (AST), (ALT), (Alk.P), (Bil), (TP), (TC). The present findings observed in this study revealed that,glimepirideis natural antioxidant lignin possess significant antioxidant activity against ccl4 induced hepatotoxicity via antioxidant mechanism. However, further research is required to find out the other possible mechanism of hepatoprotection to conform that  as glimepiridehepatoprotective molecule.

REFERENCE ID: PHARMATUTOR-ART-2424

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 4, Issue 8

Received On: 18/02/2016; Accepted On: 13/03/2016; Published On: 01/08/2016

How to cite this article: Hemavathy CVH, Kumar BR, Kumar RK, latha GH; Hepatoprotective activity of glimepiride by inducing CCl4 hepatotoxicity; PharmaTutor; 2016; 4(8); 42-48

INTRODUCTION
The liver is an important and largest organ. Hepato or hepatic is a medical term from the greek word hepar, which means liver. It has a wide range of functions, which are detoxification, protein synthesis, and production of biochemical necessary for digestion. The liver is necessary for survival; a human can only last up to 24 hours without liver function. Liver plays a major role in detoxification and excretion of many endogenous and exogenous compounds, any injury to it or impairment to its function may leads to complications on one’s health. Drug-induced liver injury (DILI) is a major health problem that challenges not only health care professionals but also the pharmaceutical industries and drug regulatory agencies. According to the United States, 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%) (Ostapowicz et al., 2002). Other hepatotoxic drugs, such as risperidone, trovafloxacin, and nefazodone, have been assigned “black box” warnings (Lasser et al., 2002). Liver damage occurs by either due to direct damage to the liver cells or due to a secondary damage resulting from obstruction of the bile flow. Rarely, it can be due to obstruction to the blood flow either in the portal vein or in the hepatic vein.

AIM & OBJECTIVE
The main objective of the study was to evaluate the hepato protective activity of glimepirideagainst CCl4 induced hepatotoxicity. Evaluate the mechanism of hepatoprotection in terms of  Liver antioxidant mechanism; Histopathological study.

REVIEW OF LITERATURE
Takashi ideet. Al.
Effect of Sesamin, a sesame lignin, on the hepatic fatty acid metabolism was examined in the rat. Increase of the dietary level of Sesamin progressively increased the mitochondrial and peroxisome fatty acid oxidation rate. Mitochondrial activity almost doubled in rats fed a 0.5% Sesamin diet. Peroxisomal activity became more than 10 times higher in rats fed a 0.5% Sesamin diet, compared to those fed a Sesamin-free diet. Dietary Sesamin also markedly increased the hepatic activity and mRNA levels of various fatty acid oxidation enzymes. In contrast, dietary Sesamin decreased the hepatic activity and mRNA abundance of lipogenic enzymes. This was associated with the down-regulation of sterol regulatory element-binding protein-1, a transcriptional factor that regulates the lipogenic enzyme gene expression. Dietary Sesamin significantly decreased the triacylglycerol secretion accompanying the increase in ketone body production by the perfused rat liver. It is apparent that Sesamin affects the fatty acid metabolism and lipoprotein production in the liver, and hence lowers the serum lipid levels.

Mehrdad Roghani et al In this study, the effect of chronic treatment with Sesamin on vascular permeability in rats with streptozotocin (STZ)-induced diabetes was investigated. Male diabetic rats received Sesamin at a dose of either 10 or 20 mg/kg for 7 weeks, beginning 1 week after diabetes induction. Vascular permeability was estimated by measuring Evans blue dye extravasation. Oxidative stress markers, including malondialdehyde (MDA) and superoxide dismutase (SOD) activity, were also measured in aortic tissue.

R. Kim et al Lignin’s constitute a group of phytochemicals, which are produced by oxidative dimerization of two phenylpropanoid units. Furfuran type lignin’s such as secoisolariciresinol, matairesinol, lariciresinol or pinoresinol are widely distributed in edible plants, and most of those dietary lignans are metabolized by the gut microflora to enterolactone and enterodiol, also known as enterolignans, traditionally classified as phytoestrogens. The rich sources of lignans are flaxseed, sesame seeds, cereal products, and Brassica vegetables. There is a growing interest in biological functions of lignans from edible plants, since a higher intake of edible plants containing lignans is known to reduce the incidence of certain chronic diseases. This review deals with the isolation and preparation of furfuran type lignans from edible plants, and their bioactivities such as anticancer, antioxidant, cardio vasculoprotective, neuro protective, and anti-inflammatory activities, so that recent informations about bioactive lignans from edible plants may be available for the development of potential functional food agents.

DRUG PROFILE
AMARYL is effective as initial drug therapy. In patients where monotherapy with AMARYL or metformin has not produced adequate glycemic control, the combination of AMARYL and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different primary mechanisms of action. This complementary effect has been observed with metformin and other sulfonylureas, in multiple studies.

The primary mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. In addition, extrapancreatic effects may also play a role in the activity of sulfonylureas such as glimepiride. This is supported by both preclinical and clinical studies demonstrating that glimepiride administration can lead to increased sensitivity of peripheral tissues to insulin. These findings are consistent with the results of a long-term, randomized, placebo-controlled trial in which AMARYL therapy improved postprandial insulin/C-peptide responses and overall glycemic control without producing clinically meaningful increases in fasting insulin/C-peptide levels. However, as with other sulfonylureas, the mechanism by which glimepiride lowers blood glucose during long-term administration has not been clearly established. In considering the use of AMARYL in asymptomatic patients, it should be recognized that blood glucose control in Type 2 diabetes has not definitely been established to be effective in preventing the long-term cardiovascular and neural complications of diabetes. However, the Diabetes Control and Complications Trial (DCCT) demonstrated that control of HbA1c and glucose was associated with a decrease in retinopathy, neuropathy, and nephropathy for insulin-dependent diabetic (IDDM)patients.

MATERIALS AND METHODS
wistar albino rats were used for the study. The animals were housed in groups of six and maintained under standard conditions (27±2ºC, relative humidity 44 - 56% and light and dark cycles of 10 and 14 hours respectively) and fed with standard rat diet and purified drinking water ad libitum for 1 week before and during the experiments.

All the experiments were performed in the morning according to current guidelines for the care of laboratory animals and the ethical guidelines for the investigation of experimental pain in conscious    animals.All the studies conducted were approved by the Institutional Animal Ethical (IAEC)(ANCP/IAEC/1026 under the OCED guidelines of 465.

EXPERIMENTAL DESIGN
The animals were divided into four groups of three animals in each group.

Group I was given with vehicle (10 ml/kg).

Group II was given with CCL4 50% v/v in tween 80 at a dose of 0.1 ml/kg on the 13th day only starting from 1st day of treatment.

Group III was given with glimepiride(10mg/kg) for 12 days starting from the first day of treatment, and on 13th day it was treated with CCl4 50% v/v in  at a dose of 0.1 ml/kg.

Group IV was given with glimepiride(20 mg/kg) for 12 days starting from the first day of treatment, and on 13th day it was treated with CCl4 50% v/v in at a dose of 0.1 ml/kg.

On the 14th day all the rats from all the groups were sacrificed, blood was collected from each animal for serum analysis  and their livers were stored under freezing conditions for the estimation of endogenous anti oxidants and one sample from each group was stored in 10% formalin for histopathological studies.

ESTIMATION OF ASPARTATE AMINO TRANSFERASE (AST) or SGOT

Method: Reitman and Frankel method.

Principle: SGOT catalyses the following reaction i.e. the transfer of an amino group from L-aspartate to α-ketoglutarate.α- Ketoglutarate + L- Aspartate ↔ L- Glutamate + Oxaloacetate. Oxaloacetate so formed is coupled with 2,4-Dinitrophenyl hydrazine (2,4-DNPH) to give the corresponding hydrazone which gives brown color in alkaline medium and this can be measured colorimetrically.

ESTIMATION OF ALANINE AMINO TRANSFERASE (ALT) or SGPT

Method: Reitman and Frankel method.

Principle: SGPT catalyses the following reaction i.e. the transfer of an amino group from L-alanine to α-ketoglutarate.

α- Ketoglutarate + L- Alanine   ↔  L- Glutamate + Pyruvate

Pyruvate so formed is coupled with 2,4-Dinitrophenyl hydrazine(2,4-DNPH) to give the corresponding hydrazone which gives brown color in alkaline medium and this can be measured colorimetrically.

ESTIMATION OF ALKALINE PHOSPHATASE (Alk.P)

Method: Kind and King’s method.

Principle: Alkaline phosphatase from serum converts phenyl phosphate to inorganic phosphate and phenol at pH 10. Phenol so formed reacts with 4-Aminoantipyrine in alkaline medium in presence of oxidizing agent potassium ferricyanide and forms an orange-red complex, which can be measured colorimetrically. The color intensity is proportional to the enzyme activity.

Phenol + 4-Aminoantipyrine → orange-red complex

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT editor-in-chief@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


Pages

FIND MORE ARTICLES