oxidative stress and the role of cumin (cuminum cyminum linn.) in...

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Oxidative Stress and the Role of Cumin (Cuminumcyminum Linn.) in Alloxan-Induced Diabetic RatsDhandapani Surya a , Ramasamy Subramanian Vijayakumar a & Namasivayam Nalini aa Department of Biochemistry , Annamalai University , Annamalainagar, 608 002, IndiaPublished online: 22 Sep 2008.

To cite this article: Dhandapani Surya , Ramasamy Subramanian Vijayakumar & Namasivayam Nalini (2005) Oxidative Stressand the Role of Cumin (Cuminum cyminum Linn.) in Alloxan-Induced Diabetic Rats, Journal of Herbs, Spices & MedicinalPlants, 11:3, 127-139, DOI: 10.1300/J044v11n03_12

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Oxidative Stress and the Roleof Cumin (Cuminum cyminum Linn.)

in Alloxan-Induced Diabetic Rats

Dhandapani SuryaRamasamy Subramanian Vijayakumar

Namasivayam Nalini

ABSTRACT. The effect of cumin (Cuminum cyminum Linn.) on tissuelipid peroxidation and antioxidants in experimental diabetes mellituswas evaluated. Albino rats, non-diabetic and diabetic [those injectedwith alloxan monohydrate (150 mg kg�1 body weight) intraperitoneallyto induce diabetes mellitus, blood glucose in the range of 200-300 mgdl�1], were used in the study. Cumin (0.25 g kg�1 body weight in dis-tilled water) was given to non-diabetic and diabetic rats everyday byintragastric incubation for six weeks. Significantly elevated levels ofthiobarbituric acid reactive substances (TBARS) and conjugated dienesand significantly reduced levels of reduced glutathione (GSH), super-oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)and glutathione-S-transferase (GST) were observed in the pancreas,liver, kidney, intestine and aorta of diabetic rats as compared with thenon-diabetic rats. Administering cumin significantly decreased thelevels of TBARS and conjugated dienes and elevated the levels ofGSH, SOD, CAT, GPx and GST in the pancreas, liver, intestine andaorta of diabetic rats as compared with the non-diabetic rats. Our data

Dhandapani Surya, Ramasamy Subramanian Vijayakumar, and Namasivayam Naliniare affiliated with the Department of Biochemistry, Annamalai University, Annamal-ainagar-608 002, India.

Address correspondence to: Namasivayam Nalini, Reader, Department of Bio-chemistry, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India(E-mail: [email protected]).

Received February 11, 2003.

Journal of Herbs, Spices & Medicinal Plants, Vol. 11(3) 2005Available online at http://www.haworthpress.com/web/JHSMP

2005 by The Haworth Press, Inc. All rights reserved.doi:10.1300/J044v11n03_12 127

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indicate that supplementation with cumin can reduce free radical medi-ated oxidative stress to the cells in experimental diabetes mellitus. [Ar-ticle copies available for a fee from The Haworth Document Delivery Service:1-800-HAWORTH. E-mail address: <[email protected]> Web-site: <http://www.HaworthPress.com> 2005 by The Haworth Press, Inc. Allrights reserved.]

KEYWORDS. Antioxidants, diabetes, glibenclamide, hypoglycemia,lipid peroxidation, medicinal plant

INTRODUCTION

Free radical production and excessive oxidative stress have been im-plicated in the pathology and complications of diabetes mellitus (41).The peroxidation process involves oxidative conversion of polyunsatu-rated fatty acids to lipid hydroperoxides as the primary product togetherwith the formation of a variety of secondary metabolites (10). Oxidativestress, an imbalance of pro-oxidants over antioxidant defense potential(35), can be mediated by regular metabolites, such as superoxide an-ions, peroxyl and alkoxyl radicals and singlet oxygen. The susceptibil-ity of the body to oxidative stress is related to the balance between thepro-oxidant load and the adequacy of antioxidant defense (1).

Dietary antioxidants may be effective against oxidative stress in liv-ing systems (7,21) and many antioxidants have been found in spices andherbs. Among the spices, cumin seeds (Cuminum cyminum Linn.), be-longing to the family Apiaceae, are consumed in fairly large quantitiesby citizens of India. Cumin seeds contain resin, mucilage, gum, pro-teins, malates and an essential oil. The oil thymene, rich in carotene,contains cuminol or cumin aldehydes, a mixture of hydrocarbons, cy-mene or cymol, terpene and other chemicals (4). Several studies haveshown that cumin has anti-hyperglycemic (30), anticarcinogenic (2),and pro-estrogenic (19) activity and inhibits platelet aggregation (39).

In this study, the antioxidant potential of cumin on lipid peroxidationand on enzymic and non-enzymic antioxidants in experimental diabetesmellitus was investigated.

MATERIALS AND METHODS

Plant Material. Cumin (Cuminum cyminum Linn.) seeds were col-lected fresh in Chidambaram, Cuddalore District, Tamil Nadu, India.

128 JOURNAL OF HERBS, SPICES & MEDICINAL PLANTS

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After thoroughly drying in the sun, the collected seeds were ground inan electric mill (Mesh number 50), separately sealed in airtight contain-ers, and placed in a deep freeze (�20°C) until used. For experimentalpurposes, the cumin powder was mixed in double distilled water just be-fore use. An analysis of the cumin powder indicated 15 percent fat, 36.6percent carbohydrate, 12 percent fiber, and 18.7 percent protein (26).

Chemicals. Alloxan was purchased from Sulab’s Laboratory, Mumbai,India. Phenazine methosulphate, nitro blue tetrazolium and nicotina-mide adenine dinucleotide (NADH) were purchased from HimediaLaboratory Limited, Mumbai, India. Glutathione and 5, 5�-dithio 2-ni-tro bis benzoic acid were purchased from Sigma Chemical Company,MO, St. Louis, USA. Sodium azide, thiobarbituric acid and 1-chloro 2,4-dinitro benzene were purchased from Central Drug House (P) Ltd.,Mumbai, India.

Test Animals. Female albino Wistar rats (body weight 75-110 g) bredin the Central Animal House, Raja Muthiah Medical College, AnnamalaiUniversity, Annamalainagar were used in this study. The animals werehoused in plastic cages with filter tops under controlled conditions with12 h light/12 h dark cycle, 50 percent relative humidity, and at 28°C.The rats were maintained on a standard pellet diet (Hindustan LeverLimited, India) and water ad libitum. Care of all animals used in thepresent study were as per the principles and guidelines of the EthicalCommittee of Animal Care of Annamalai University and in accordancewith the Indian National Law on Animal Care and Use.

To induce diabetes, the rats were injected intraperitonealy with a sin-gle dose of 150 mg kg�1 body weight alloxan monohydrate dissolved insterile normal saline. Since alloxan is capable of producing fatal hypo-glycemia as a result of massive pancreatic insulin release induced byalloxan, the rats were given 20 percent glucose solution orally instead ofdrinking water after 6 h of alloxan injection. For the next 24 h, the ratswere then kept on five percent glucose solution to prevent hypoglycemia.

After a fortnight, rats with moderate diabetes having glycosuria (in-dicated by Benedict’s test of the urine) and hyperglycemia (indicated bya blood glucose range of 200-300 mg dl�1) were used in the experimen-tal procedure. Blood samples were collected from the tail vein.

Experimental. A total of 60 rats (36 surviving diabetic rats and 24non-diabetic rats) were used in the experiment. At two weeks after in-duction of diabetes, the rats were divided into five groups of 12 rats eachfor experimental treatments (Table 1). The low dose of cumin used wasdetermined by reference to the average human daily intake recorded in a

Surya, Vijayakumar, and Nalini 129

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survey conducted in India (38). Glibenclamide was used as a referencedrug.

The animals were closely monitored everyday, weighed every week,and tested for urine sugar and blood glucose. At the end of six weeks,the animals were subjected to an overnight fast and administered lightether anesthesia before sacrificing by cervical dislocation. Blood wascollected and processed for estimation of blood glucose. Tissues, suchas liver, kidney, pancreas, intestine, and aorta were cleared of adheringfat, weighed, homogenized with suitable buffer, and used for the variousestimations.

Biochemical Measurements. Fasting blood glucose was estimated bythe O-toluidene method (32). Lipid peroxidation was estimated by mea-surement of thiobarbituric acid reactive substances (TBARS) in plasmaby the method of Yagi (42) with the pink chromogen produced by thereaction of thiobarbituric acid with malondialdehyde, a secondary prod-uct of lipid peroxidation, estimated at 532 nm. Conjugated dienes wereestimated by the method of Rao and Recknagel (29) based on the ar-rangement of double bonds in polyunsaturated fatty acids (PUFA) toform conjugated dienes with an absorbance maximum at 233 nm.

Reduced glutathione (GSH) was determined by the method of Ellman(8) and based on the development of a yellow color when 5, 5�-dithio2-nitrobenzioc acid (DTNB) is added to compounds containing sulfhydrylgroups. Glutathione peroxidase (GPx, EC. 1.11.1.9) activity was as-sayed by the method of Rotruck et al. (31) with modifications: a knownamount of enzyme preparation was incubated with H2O2 in the presenceof GSH for a specified time period and the amount of H2O2 utilized wasdetermined by the method of Ellman (8). The activity of glutathione-S-transferase (GST, EC. 2.5.1.18) was estimated by the method of


TABLE 1. Experimental treatments.

Treatment Designation

Non-diabetic control rats Group 1 = non-diabetic

Non-diabetic control rats given cumin (0.25 g kg�1 body weight) dailyin 0.5 ml of distilled water using an intragastric tube for 6 weeks

Group 2 = non-diabetic + cumin

Diabetic rats Group 3 = diabetic

Diabetic rats given cumin (0.25 g kg�1 body weight) daily in 0.5 ml ofdistilled water using an intragastric tube for 6 weeks

Group 4 = diabetic + cumin

Diabetic rats given glibenclamide (0.6 mg kg�1 body weight) daily in0.5ml distilled water using an intragastric tube for 6 weeks

Group 5 = diabetic + glibenclamide

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Habig et al. (11) by following the increase in absorbance at 340 nm us-ing 1-chloro, 2, 4 dinitrobenzene (CDNB) as substrate.

Superoxide dismutase (SOD, EC. 1.15.1.1) was assayed by the methodof Kakkar et al. (15), based on the 50 percent inhibition of the formationof NADH-phenazine methosulphate-nitroblue tetrazolium at 520 nm.The activity of catalase (CAT, EC. 1.11.1.6) was assayed by the methodof Sinha (36) based on the utilization of hydrogen peroxide by the en-zyme. Proteins were estimated by the method of Lowry et al. (18).

Statistical Analysis. All the results are expressed as the mean ± SD of12 rats in each test group. Students t-test was used to determine significantdifferences among means. A one way analysis of variance (ANOVA)was done and the F-ratio was calculated (6). The results were consid-ered statistically significant at P < 0.05.

RESULTS

Significant weight loss was observed in diabetic rats as comparedwith non-diabetic control animals (Table 1). Treatment with cumin orglibenclamide significantly improved the weight gain as compared withdiabetic animals.

The blood glucose and urine sugar were significantly (P < 0.05) in-creased in alloxan diabetic rats as compared with the non-diabetic con-trol rats (Table 2). Administration of cumin or glibenclamide tended tobring the blood glucose and urine sugar values near to those of the


TABLE 2. Effect of cumin and glibenclamide on weight gain.

Test animals1Initial weight Final weight

(g)2 (g)2

Non-diabetic 156 ± 0.81 220 ± 1.82

Non-diabetic + cumin 153 ± 1.29 205 ± 1.82*

Diabetic 160 ± 1.29 132 ± 1.15*

Diabetic + cumin 158 ± 2.08 195 ± 0.81^

Diabetic + glibenclamide 150 ± 2.30 180 ± 0.81^

F-ratio3 215.46 91.15

1 Groups of diabetic and non-diabetic rats received treatments indicated in Table 1.2 Means ± SD, n = 6; *, ^ = significantly different as compared with relevant control, non-diabetic and diabetic, re-spectively. P < 0.05 (T-test, 10 d.f.).3 F-ratios were significant at the 5% level.

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non-diabetic control rats. The effect of cumin on blood glucose levels indiabetic rats was more pronounced than glibenclamide.

TBARS and conjugated dienes were elevated in the diabetic liver,kidney, pancreas, intestine, and aorta as compared with the non-diabeticrat tissues (Tables 3 and 4). Supplementing diabetic rats with cumin andglibenclamide significantly reduced the levels of TBARS and conju-gated dienes as compared with untreated diabetic rats.


TABLE 3. Effect of cumin on blood glucose and urine sugar.

Test animals1Blood glucose Urine sugar

(mg dl�1)2

Non-diabetic 67.31 ± 4.56 Nil

Non-diabetic + cumin 63.87 ± 6.55* Nil

Diabetic 236.57 ± 12.89* +++

Diabetic + cumin 82.00 ± 9.27^ +

Diabetic + glibenclamide 103.33 ± 15.48^ +

F- ratio3 280.57

1 Groups of diabetic and non-diabetic rats received treatments indicated in Table 1.2 Means ± SD, n = 6; *, ^ = significantly different as compared with relevant control, non-diabetic and diabetic, re-spectively. P < 0.05 (T-test, 10 d.f.).3 F-ratio was significant at the 5 % level.

TABLE 4. Effect of cumin on thiobarbituric acid reactive substances in tissues.

Test animals2

TBARS1

Liver Pancreas Kidney Intestine Aorta

(nM of MDA formed g�1 tissue)3

Non-diabetic 33.80 ± 4.09 39.43 ± 4.83 25.30 ± 2.89 23.94 ± 2.26 51.87 ± 5.41

Non-diabetic +cumin

30.57 ± 3.77 32.52 ± 4.29 23.64 ± 3.07 21.45 ± 2.69 48.83 ± 4.95

Diabetic 70.60 ± 7.50*** 64.44 ± 7.06*** 77.55 ± 8.18*** 71.75 ± 7.85*** 98.76 ± 9.27***

Diabetic + cumin 41.80 ± 5.11^^^ 41.73 ± 4.81^^^ 53.68 ± 5.97^^^ 32.71 ± 4.10^^^ 72.74 ± 7.24^^^

Diabetic +glibenclamide

36.55 ± 4.48^^^ 40.63 ± 4.81^^^ 56.90 ± 5.28^^^ 27.65 ± 3.32^^^ 70.00 ± 7.69^^^

F-ratio4 58.57 31.91 105.82 126.21 47.71

1 TBARS = thiobarbituric acid reactive substances.2 Groups of diabetic and non-diabetic rats received treatments indicated in Table 1.3 Means ± SD, n = 6; *, ^ = significantly different as compared with relevant control, non-diabetic and diabetic, re-spectively. ***, ^^^ = P < 0.001 (T-test, 10 d.f.).

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The concentration of GSH in the liver, kidney, pancreas, intestine,and aorta were decreased in diabetic rats as compared with the controlrat tissues (Table 5). Administering cumin and glibenclamide to dia-betic rats significantly elevated the concentration of glutathione as com-pared with the untreated diabetic rats.

The activity of superoxide dismutase, catalase, glutathione peroxi-dase and glutathione-S-transferase were significantly decreased in theliver, kidney, pancreas, intestine and aorta of diabetic rats as comparedwith non-diabetic control rats (Tables 6, 7, 8, 9 and 10). Administeringcumin and glibenclamide to the diabetic rats increased the activity of allthese enzymes significantly as compared with the untreated diabeticrats.

DISCUSSION

Alloxan, known to be a β-cytotoxin, produces a chemically induceddiabetes (alloxan diabetes) in a wide variety of animal species by dam-aging the insulin secreting cells of the pancreas. Alloxan diabetic ratsbecome hyperglycemic and under increased oxidative stress (25). Ourobservations in this study, correlates with previous research findings inthat the blood glucose levels were elevated significantly in alloxan dia-


TABLE 5. Effect of cumin on conjugated dienes in tissues.

Test animals1

Conjugated dienes


(µM g�1 tissue)2

Non-diabetic 196.79 ± 22.43 170.79 ± 19.83 180.68 ± 20.83 133.79 ± 14.79 456.78 ± 51.65

Non-diabetic +cumin

191.93 ± 20.64 164.59 ± 17.73 190.65 ± 19.90 132.10 ± 15.28 499.08 ± 50.25

Diabetic 301.70 ± 32.35*** 363.68 ± 39.95*** 379.57 ± 42.43*** 313.43 ± 38.48*** 700.51 ± 76.69***

Diabetic +cumin

210.46 ± 22.86^^^ 167.41 ± 18.10^^^ 152.17 ± 17.14^^^ 186.69 ± 20.26^^^ 467.24 ± 48.97^^^


196.48 ± 20.26^^^ 163.54 ± 16.85^^^ 139.29 ± 15.03^^^ 171.61 ± 20.31^^^ 486.60 ± 52.46^^^

F- ratio3 22.28 80.01 92.18 60.04 18.90

1 Groups of diabetic and non-diabetic rats received treatments indicated in Table 1.2 Means ± SD, n = 6; *, ^ = significantly different as compared with relevant control, non-diabetic and diabetic, re-spectively. ***, ^^^ = P < 0.001 (T-test, 10 d.f.).3 F-ratios were all significant at the 5 % level.

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betic rats. Moreover, administering cumin extract to the diabetic ratssignificantly reduced the blood glucose levels. Willatgamuwa et al. (40)have also observed a remarkable decrease in the blood sugar levels indiabetic rats administered cumin. The possible mechanism by whichcumin brings about hypoglycaemic action may be by potentiating theinsulin effect, either by increasing the pancreatic secretion of insulin


TABLE 6. Effect of cumin on reduced glutathione in tissues.

Test animals1

GSH


(mg g�1 tissue)2

Non-diabetic 21.56 ± 2.14 13.76 ± 1.99 21.70 ± 1.94 17.65 ± 2.00 13.50 ± 1.87

Non-diabetic +cumin

24.62 ± 2.01 13.76 ± 1.58 22.55 ± 1.86 15.63 ± 2.17 14.67 ± 1.84

Diabetic 12.47 ± 2.05*** 6.17 ± 0.34*** 15.69 ± 2.17*** 7.23 ± 1.42**^ 3.53 ± 0.32**^

Diabetic + cumin 18.57 ± 2.05^^^ 9.58 ± 1.42^^^ 20.40 ± 3.05^^ 16.67 ± 2.03^^^ 11.39 ± 1.50^^^


15.37 ± 2.11^ 12.52 ± 1.48^^^ 20.53 ± 2.16^^ 12.59 ± 2.06^^^ 11.41 ± 1.48^^^

F-ratio3 32.43 29.64 8.18 27.78 49.67

1 Groups of diabetic and non-diabetic rats received treatments indicated in Table 1.2 Means ± SD, n = 6; *, ^ = significantly different as compared with relevant control, non-diabetic and diabetic, re-spectively. ***, ^^^ = P < 0.001; **, ^^ = P < 0.01; *, ^ P < 0.01 (T-test, 10 d.f.).3 F-ratios were all significant at the 5 % level.

TABLE 7. Effect of cumin on superoxide dismutase in tissues.

Test animals1

SOD


(units min�1 mg protein�1)2

Non-diabetic 4.44 ± 0.83 4.64 ± 0.71 3.68 ± 0.33 2.76 ± 0.42 4.54 ± 0.30

Non-diabetic +cumin

4.21 ± 0.48 4.07 ± 0.38 3.63 ± 0.38 2.74 ± 0.35 4.81 ± 0.50

Diabetic 1.18 ± 0.25* 0.97 ± 0.17* 1.07 ± 0.19* 0.47 ± 0.10* 1.17 ± 0.16^

Diabetic + cumin 4.14 ± 0.41^ 3.32 ± 0.16^ 3.09 ± 0.38^ 2.84 ± 0.38^ 3.98 ± 0.49^


3.75 ± 0.34^ 3.12 ± 0.35^ 3.54 ± 0.37^ 2.60 ± 0.44^ 4.16 ± 0.38^

F-ratio3 42.69 69.23 61.81 47.05 84.56

1 Groups of diabetic and non-diabetic rats received treatments indicated in Table 1.2 Units = 50 % inhibition of NBT reduction; means ± SD, n = 6; *, ^ = significantly different as compared with relevantcontrol, non-diabetic and diabetic, respectively. ***, ^^^ = P < 0.001; **, ^^ = P < 0.01; *, ^ P < 0.01 (T-test, 10 d.f.).3 F-ratios were all significant at the 5 % level.

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from the cells of Islets of Langerhan’s or the release of insulin frombound insulin. In this context, a number of other plants and plantproducts have also been observed to have hypoglycemic effects (23,27,28,30).

Lipid peroxide mediated tissue damage has been observed both intype I and type II diabetes mellitus (9,12). Hyperglycemia generates


TABLE 8. Effect of cumin on catalase activity in tissues.

Test animals1

CAT


(µmoles H2O2 consumed min�1 mg protein�1)2

Non-diabetic 67.40 ± 6.81 74.36 ± 6.68 56.39 ± 5.18 44.55 ± 5.00 30.41 ± 3.65

Non-diabetic +cumin

60.68 ± 6.54 74.87 ± 6.83 54.36 ± 6.39 40.50 ± 5.21 28.78 ± 3.69

Diabetic 34.61 ± 4.24* 33.84 ± 3.31* 32.46 ± 3.90* 17.99 ± 2.22* 13.10 ± 1.99*

Diabetic + cumin 64.47 ± 6.59^ 74.43 ± 7.19^ 5.53 ± 6.28^ 41.68 ± 4.94^ 24.36 ± 3.04^


61.98 ± 6.44^ 60.32 ± 6.61^ 38.63 ± 4.40^ 44.43 ± 4.52^ 25 ± 3.16^

F-ratio3 27.28 47.61 25.31 37.07 27.37

1 Groups of diabetic and non-diabetic rats received treatments indicated in Table 1.2 Units = 50% inhibition of NBT reduction; means ± SD, n = 6; *, ^ = significantly different as compared with relevantcontrol, non-diabetic and diabetic, respectively. ***, ^^^ = P < 0.001; **, ^^ = P < 0.01; *, ^ P < 0.01 (T-test, 10 d.f.).3 F-ratios were all significant at the 5% level.

TABLE 9. Effect of cumin on glutathione peroxidase activity.

Test animals1

GPx


(µmoles GSH consumed min�1 mg protein�1)2

Non-diabetic 20.68 ± 1.88 31.59 ± 3.31 18.53 ± 2.20 23.45 ± 2.19 29.72 ± 2.58

Non-diabetic +cumin

22.50 ± 2.06 32.61 ± 3.31 20.60 ± 1.99 22.55 ± 2.13 47.16 ± 2.71

Diabetic 7.27 ± 1.27* 17.60 ± 1.81* 5.60 ± 0.75* 12.59 ± 1.96* 12.76 ± 1.89*

Diabetic + cumin 17.42 ± 2.06^ 32.34 ± 3.30^ 16.62 ± 1.10^ 22.23 ± 2.08^ 24.73 ± 2.67^


15.44 ± 1.62^ 32.56 ± 3.40^ 15.70 ± 1.85^ 22.52 ± 1.97^ 26.47 ± 2.52^

F-ratio3 64.37 27.14 71.77 28.74 47.16


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abnormally high levels of free radicals by a process that involvesautoxidation of glucose followed by oxidative degeneration and proteinglycation (13). In this context, increased levels of TBARS in the liverand kidney of alloxan diabetic rats can be expected (5). In the presentstudy, we have also observed significantly elevated levels of TBARSand conjugated dienes (an intermediate formed during lipid peroxi-dation) in the liver, kidney, pancreas, and aorta of alloxan induced dia-betic rats. Cumin is known to contain cuminol, a component that canlower lipid peroxidation by maintaining the activities of enzymic andnon-enzymic antioxidants. Thus, the presence of cuminol in cumincould account for the significantly reduced levels of TBARS and conju-gated dienes observed in the liver, kidney, pancreas, intestine, and aortaof diabetic rats treated with cumin in this study.

GSH, a cellular non-protein thiol in conjunction with GPx and GST,plays an important role in protecting cells against cytotoxic chemicalsby scavenging reactive oxygen species (34). Depletion of hepatic GSHand increased lipid peroxidation are characteristic of diabetes (22) andthe activities of glutathione dependent enzymes are altered in varioustissues of diabetic rats (16,20,33). We have also observed lowered lev-els of GSH, GPx and GST in the liver, kidney, pancreas, intestine, andaorta of alloxan diabetic rats. Supplementing the rat diet with cumin ele-vated the levels of GSH, GPx and GST in diabetic rats. The effect ofcumin on GSH and phase II enzymes, such as GPx and GST, may be


TABLE 10. Effect of cumin on glutathione-S-transferase activity.

Test animals1

GST


(µmoles CDNB-GSH conjugate formed min�1 mg protein�1)2

Non-diabetic 25.57 ± 2.92 33.62 ± 3.53 7.47 ± 0.91 10.35 ± 1.10 9.58 ± 0.95

Non-diabetic +cumin

24.57 ± 2.32 34.45 ± 3.47 7.46 ± 0.76 9.56 ± 0.79 9.49 ± 1.32

Diabetic 9.56 ± 0.99* 14.27 ± 1.55* 2.46 ± 0.31* 3.32 ± 0.23* 3.55 ± 2.70*

Diabetic + cumin 23.69 ± 2.49^ 32.16 ± 3.30^ 6.76 ± 0.39^ 7.55 ± 0.45^ 9.05 ± 0.96^


24.46 ± 2.15^ 30.77 ± 2.73^ 7.04 ± 0.52^ 8.03 ± 0.63^ 8.87 ± 0.67^

F-ratio3 52.81 46.48 69.32 88.30 47.00


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considered a generalized electrophilic counter attack response evokedby alloxan. We speculate that modulation of lipid peroxidation and en-hanced elevation of alloxan detoxification systems such as GST aremajor mechanisms by which cumin exerts a chemopreventive effect ontissues.

Superoxide and hydroxyl radicals, important mediators of oxidativestress, induce various injuries to the surrounding organs and play a vitalrole in some clinical disorders (37). Any compound, natural or syntheticwith antioxidant activities might contribute to the total or partial allevia-tion of this tissue damage. Therefore, removing superoxide and hydroxylradicals would be the most effective defense of a living body againstcertain diseases (14). SOD converts superoxide into hydrogen peroxideand subsequently CAT acts to convert the hydrogen peroxide to H2O.Reduced SOD and CAT activity in the liver, kidney, pancreas, intestine,and aorta were observed in the diabetic rats. Lowered activities of theseenzymes may result in a number of deleterious effects. The non-enzy-matic glycosylation of those enzymes that normally detoxify free radi-cal species may exacerbate oxidative stress in diabetes (3). In thiscontext other workers have also reported a decrease in the activities ofSOD and CAT in alloxan induced, diabetic rat tissue such as liver, kid-ney, pancreas, and brain (17). Administering cumin and glibenclamideincreased the activities of SOD and CAT in the liver, kidney, pancreas,intestine, and aorta of diabetic rats. These results show that cumin pos-sesses antioxidant activity that could exert a beneficial action againstpathological alterations caused by the presence of superoxide andhydroxyl radicals in alloxan-induced diabetes.

The present study suggests that cumin exerts a protective effect intype I diabetes mellitus by decreasing the oxidative stress, increasingGSH content, and maintaining normal levels of the antioxidant enzymesSOD, CAT, GPx, and GST. The effect of the cumin was more pro-nounced in lowering the oxidative stress to cells of the liver, pancreas,kidney and aorta than the reference drug glibenclamide. More researchis needed to ascertain the effects of long term administration of cumin.

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oxidative stress and the role of cumin (cuminum cyminum linn.) in...

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