GARCINIA CAMBOGIA AND ETHANOL INDUCED PEROXIDATION

Indian Journal of Pharmacology 2001; 33: 87-91 SHORT COMMUNICATION

Correspondence: C.S. Shyamala Devi

THE MODULATING EFFECT OF GARCINIA CAMBOGIA EXTRACT ON ETHANOLINDUCED PEROXIDATIVE DAMAGE IN RATS

P. MAHENDRAN, C.S. SHYAMALA DEVI

Department of Biochemistry & Molecular Biology, University of Madras, Guindy Campus,Chennai - 600 025.

Manuscript Received: 25.5.2000 Revised: 14.6.2000 Accepted: 13.7.2000

Objective: To determine the modulating effect of Garcinia cambogia fruit extract on ethanol inducedperoxidative damage in rats.Method: Male albino rats weighing 125 to 150g were administered ethanol (7.11g per kg body weight /day) for 45 days. Ethanol administered rats were treated concomitantly with Garcinia cambogia fruitextract (1g/kg body weight / day) orally for 45 days. After the experimental period the antioxidant enzymes,LPO, conjugated diene in the liver tissue, serum AST, ALT and alkaline phosphatase and lipid levels inboth serum and liver tissue were estimated.Results: Co-treatment of the rats with Garcinia cambogia significantly inhibited the rise in lipid levelsand also the peroxidative damage caused by ethanol, which is evident from the improved antioxidantstatus. The levels of serum AST, ALT and alkaline phosphatase were maintained at near normalcy inGarcinia cambogia treated rats.Conclusion: The imbalance in lipid metabolism could be the reason for increase in lipid peroxidation. Inour present study the treatment with Garcinia cambogia fruit extract resulted in reduction of both serumand liver lipid to near normalcy. This hypolipidemic property of Garcinia cambogia in turn reduces theperoxidative damage, enhanced by ethanol.

Ethanol Garcinia cambogia lipid peroxidation hyperlipidemia antioxidant enzymes

SUMMARY

KEY WORDS

INTRODUCTION

Liver being the major site for detoxification is the pri-mary target for environmental or occupational toxicexposure1. The alcoholic liver injury appears to begenerated by the effects of ethanol metabolism andthe toxic effects of acetaldehyde which may be me-diated by acetaldehyde altered proteins2. Chronicalcohol intake is known to produce hypercholestero-lemia, hyperlipidemia, hypertriglyceridemia3,4. Inchronic lipid accumulation the liver cells become fi-brotic and leads to impaired liver function. Enhancedlipid peroxidation has been reported in hyper-lipidemia5, which is also induced by ethanol3,4. Etha-nol increases triglycerides and cholesterol levels thusinducing imbalance in lipid metabolism in liver, heart,kidney and other organs and this could explain thereason for the increase in lipid peroxidation in theseorgans. Recently free radical induced lipid peroxida-tion has gained much importance because of its in-

volvement in several pathologies6,7. Protection of cellmembrane from lipid peroxidation becomes a neces-sity to prevent, cure or delay the aforesaid patho-logies.

Rind of the fruits of Garcinia cambogia (Gaertn.)Desr. (Clusiaceae) is an astringent and is useful inthe treatment of ulcers, haemorrhoids, diarrhoea anddysentry8,9. Garcinia cambogia fruit extract, contain-ing the principle organic acid, (-)-erythro-Ls-hydroxycitric acid is a powerful anti-lipogenic agent10.The present study is an attempt to elucidate theantiperoxidative property of Garcinia cambogia onethanol induced peroxidative damage and its efficacyto inhibit lipid peroxidation.

MATERIALS AND METHODS

Animals: Male albino rats weighing 125 to 150 gwere purchased from FIPPAT, Padappai, Chennai.The animals were housed in plastic bottom cages

P. MAHENDRAN AND C.S. SHYAMALA DEVI

Table 1. Serum and hepatic levels of total cholesterol, triglycerides, free fatty acids, phospholipids, alkaline phosphatase, aspartateamino transferase (AST), alanine amino transferase (ALT) in experimental groupsa.

I II III IV ANOVAParametersb Control Group 18% Ethanol treated Garcinia cambogia Garcinia cambogia F value*

(n = 6) group (n = 6) treated group + 18% ethanol treated(n = 6) group (n = 6)

Total cholesterol A 70.4 1.18 113.2 2.19*** 64.3 1.26*** 72.2 1.81*** 4.24B 4.36 0.37 6.82 0. 51*** 3.72 0.51* 4.76 0.40*** 2.88

Triglycerides A 107.8 2.08 156.0 2.14*** 98.5 2.09*** 112.9 2.11*** 3.97B 4.23 0.41 5.87 0.50*** 3.73 0.46* 4.54 0.40*** 2.94

FFA A 64.1 1.96 115.4 2.28*** 56.6 1.64*** 70.8 2.07*** 3.68B 11.5 0.93 21.6 1.67*** 9.9 0.81** 13.2 1.24*** 3.24

Phospholipids A 115.6 2.06 142.4 2.17*** 110.3 1.98** 126.7 2.23*** 3.07B 23.1 2.15 38.7 1.83*** 20.6 1.91* 30.4 1.47*** 2.90

Alkaline Phosphatase A 0.76 0.05 1.57 0.04*** 0.69 0.04NS 0.86 0.03*** 2.78B 1.41 0.04 0.88 0.03*** 1.34 0.05NS 1.19 0.04*** 2.91

AST A 0.48 0.04 0.83 0.03*** 0.41 0.04NS 0.52 0.04*** 2.83B 0.72 0.06 0.46 0.04*** 0.78 0.05NS 0.69 0.05*** 2.79

ALT A 0.63 0.04 0.92 0.04*** 0.61 0.04NS 0.58 0.03*** 2.96B 1.04 0.03 0.68 0.02*** 1.07 0.03NS 0.93 0.03*** 2.81

A : Serum B : Liver. aValues are expressed as mean SD for 6 animals in each group.Students t test: Group II vs Group I, Group III vs Group I, Group IV vs Group II. *p < 0.05; **p < 0.01; ***p < 0.001bThe values of lipids in serum are expressed as mg/dl. The values of AST, ALT and ALP in serum are expressed as kat/litre.The levels of AST and ALT in liver are expressed as moles of pyruvate liberated/sec/g protein. The level of ALP in liver is expressedas moles of phenol liberated/sec/g protein.

F - test, * Significant at level of 5% (2.77).

and allowed free access to standard laboratory chow(Hindustan Lever Foods, Bangalore, India) and water.Drug: Garcinia cambogia fruit extract was obtainedfrom Siris Herbex, Vijayawada, India. Absolute alco-hol (99%) was purchased from Anilax Chemicals,USA. All other chemicals used for the experimentwere of analytical grade.

Grouping

Group I - Normal Control (n = 6).Group II - Rats given 18% ethanol (7.11g/kg body

weight day) 5 ml/100 g body weight for45 days (n = 6).

Group III - Normal rats given Garcinia cambogia

1 g/kg body weight/day orally for 45 days(n = 6).

Group IV - Rats given 18% ethanol (7.11g/kg/bodyweight/day) + Garcinia cambogia, 1 g/kg body weight/day for 45 days (n = 6).

After the experimental period the overnight fastedrats were sacrificed by cervical dislocation. Blood andtissues were collected in ice-cold containers for vari-ous estimations.

AST, ALT11 and alkaline phosphatase11 were esti-mated in the serum. SOD12, CAT13, GSH14, GSH-Px15,GST16, LPO17 and conjugated dienes18 were esti-mated in the liver tissue. Total cholesterol19phospholipids20,21, triglycerides22 FFA23 and protein24were estimated both in serum and tissue.

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GARCINIA CAMBOGIA AND ETHANOL INDUCED PEROXIDATION

Table 2. The level of lipid peroxide, conjugated diene and activities of antioxidant enzymes in the liver of experimental groupsa.

I II III IV ANOVAParametersb Conrol group 18% Ethanol Garcinia cambogia Garcinia cambogia + F value*

(n = 6) treated group treated group 18% ethanol treated(n = 6) (n = 6) group (n = 6)

SOD 59.8 2.56 26.4 0.98*** 62.2 2.34NS 54.4 1.76*** 3.68

CAT 72.6 3.14 44.5 3.52*** 70.8 2.26NS 66.7 2.82*** 3.20

LPO 3.87 0.18 7.21 0.10*** 3.70 0.12NS 4.06 0.09*** 2.79

Conjugated diene 74.8 0.69 98.3 1.14*** 73.6 0.75NS 81.2 0.97*** 3.54

GST 152.6 3.46 81.8 2.85*** 155.4 3.71NS 151.3 2.97*** 4.12

GSH-px 175.2 6.82 102.7 5.84*** 182.3 7.06NS 171.8 5.44*** 3.96

GSH 5.11 0.05 2.16 0.08*** 4.89 0.09NS 4.32 0.04*** 2.84

aValues are expressed as mean SD for 6 animals in each groupStudents t test: Group II vs Group I, Group III vs Group I, Group IV vs Group II. ***p

P. MAHENDRAN AND C.S. SHYAMALA DEVI

the esterification of cholesterol in the plasma. In-crease in serum cholesterol, in the present study inalcohol treated rats may possibly be the result ofdecreased activity of this enzyme27.

Increase in serum triglycerides in alcohol treated ratsmay be due to decreased activity of lipoprotein li-pase which is involved in the uptake of triglyceriderich lipoprotein by extra hepatic tissue. Increasedsynthesis or decreased lipid deposition or both re-sulted in simultaneous accumulation of lipids in theblood and in the liver27.

Ethanol induces hyperlipidemia3,4 and hyperlipidemiaenhances lipid peroxidation5 causing hepatotoxicity byincreasing the free radical formation which in turn in-creases the level of lipid peroxides in hepatic tissue.

Garcinia cambogia containing the principal organicacid (-)-erythro-Ls-hydroxycitric acid is an effectiveinhibitor of ATP-citrate lyase which cleaves citrate toproduce acetyl CoA.10 (-)-hydroxycitrate suppressesbiosynthesis of both fatty acids and cholesterol in rathepatocytes28,29 and in rat liver,30 hence cholesteroland triglyceride levels are drastically reduced inGarcinia cambogia treated experimental rats (GroupIV). The reduction in lipids indirectly lowers the levelof peroxides due to hyperlipidemia.

The two antiperoxidative enzymes namely SOD andCAT decreased significantly in the hepatic tissues ofalcohol administered rats suggesting the increaseddamage to this tissue as a result of uncontrolled gen-eration of partially reduced oxygen species. The lev-els of AST, ALT and alkaline phosphatase in the se-rum have been elevated in ethanol treated rats sug-gesting hepatotoxicity as a result of high ethanol in-take31.

Garcinia cambogia, an effective antilipogenic agent32,prevents the hepatic cells to become fibrotic and thecellular damage due to hyperlipidemia. This is evi-dent from the near normal activities of transferasesand ALP in the liver of Garcinia cambogia treatedgroup (Table 1).Glutathione protects the hepatocytes by combiningwith the reactive metabolites and thereby preventingtheir covalent binding to liver protein31. Liver glutath-ione after alcohol administration was found to de-crease due to increased utilization by the hepato-cytes because GSH seems to act as scavengers for

toxic chemical agents. The non availability of glutath-ione decreases the activity of glutathione peroxidaseand glutathione transferase. Glutathione acts as thesubstrate for both GSH-Px and GST. Depletion ofglutathione will render the enzymes (GSH-Px & GST)inactive and/or less active.

It was established that the content of primary(acylhydroperoxide) and secondary (intermolecularseams in aminophospholipids) products of lipidperoxide oxidation in blood of patients with the back-ground of hyperlipidemia and hypercholesterolemiaincreased intensively33. Also in our present study thelevels of LPO and conjugated dienes increased sig-nificantly in the ethanol administered rats suggest-ing its pathogenic role. Treatment of rats with Garciniacambogia inhibited the deleterious process of lipidperoxidation and maintained the levels of glutathioneto near normalcy.

The observed abnormalities in the liver and serummay be in part due to hyperlipidemia leading tochanges in the activity of antiperoxidative enzymes,glutathione and increased lipid peroxidation. Garciniacambogia modulates its antiperoxidative role by in-hibiting hyperlipidemia and peroxidation ofbiomembranes which is sufficient to cause cell deathwhen uncontrolled.

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