World Applied Sciences Journal 33 (6): 854-865, 2015 ISSN 1818-4952 © IDOSI Publications, 2015 DOI: 10.5829/idosi.wasj.2015.33.06.14589

Effect of Some Levels of Cardamom,

Clove and on Hepatotoxicity in Rats Caused by CCL4

Shimaa M.H. Aboelnaga

Home Economic Department, Faculty of Education, Hail University, KSA

Abstract: The aim of this study was to investigate the effect of three levels of cardamom, and anise on rats suffering from hepatotoxicity. Fifty five male albino rats (Sprague Dawley Strain) used in this study, the rats divided into eleven groups. The first and second groups fed on basal diet as a control negative and positive groups. The third, fourth and fifth groups were fed on basal diet containing (2%, 4% and 6% cardamom, respectively), the sixth, seventh and eighth groups were fed on basal diet containing (2%, 4% and 6% clove, respectively), the ninth, tenth and eleventh groups were fed on basal diet containing (2%, 4% and 6% anise, respectively). On the 27 day of the experiment, all animals, except the negative control group was

administered subcutaneous injection 20% CCl4 in liquid paraffin oil at a dose 5 ml/kg body weight to induce hepatotoxicity in rats. During the experimental period (28 days), the diets consumed and body weights were recorded twice weekly, at the end of the experiment period, the rats were fasted overnight, then the rats were anaesthetized and sacrificed and the blood samples were collected from the aorta. The blood samples were centrifuged and serum was separated to determine some biochemical parameters. Results showed that,

feeding rats on basal diet and injected with CCl4 (control positive group) induced non-significant changes in fed intake and body weight gain %, while liver and kidney weights, liver enzymes, lipid profile, except HDL-c, glucose and kidney functions increased significantly increase p?0.5, as compared to the rats fed on basal diet in the first main group (control negative group). Treating rats which suffer from hepatotoxicity with the three levels from (cardamom, clove and anise) decreased body weight gain%, liver and kidney weights/body weight%, serum AST, ALT, ALP, cholesterol, triglycerides, LDL-c, VLDL-c, uric acid, urea nitrogen, creatinine, glucose, while HDL-c increased. The highest improvement in these parameters recorded for the group which treated with the high level of clove (6%). In conclusion, the results of this study demonstrate that clove, cardamom and anise increased antioxidant activity and improved hepatotoxicity of rats.

Key words: Rats CCl4 Hepatotoxicity Lipids Profile Liver Enzymes Glucose Kidney Functions

INTRODUCTION induced, as expected, pathological changes in the liver, markedly increased plasma aminotransferases and alkaline Liver play an essential role in the metabolism of phosphatase activities, (used for assessing liver function) foreign compounds entering the body. Human beings are [2, 3]. Recently, interest in the discovery of natural exposed to these compounds through environmental antioxidants has risen exponentially. Principal candidates exposure, consumption of contaminated food or during in this discovery process are medical [4]. There are exposure to chemical substances in the occupational many and seeds contain a high proportion of environment. All these compounds produce a variety of antioxidants are concentrated in the form of flavonoids, toxic manifestations [1]. Carbon tetrachloride (CCl4 ) which are derivatives of polyphenols may contribute to causes acute and chronic hepatic damage due to free counteract the oxidation pressures caused by toxic radical generation. Long-term intraperitoneal compounds in the human body and work to neutralize administration of CCl4 , 50 % solution in olive oil (1 ml/kg), them [5]. Spices and are an excellent source of to rats twice a week for 10 weeks to experimental animals phenolic compounds (flavonoids, phenolic acid and

Corresponding Author: Shimaa M.H. Aboelnaga, Home Economic Department, Faculty of Education, Hail University, KSA. E-mail: [email protected]. 854 World Appl. Sci. J., 33 (6): 854-865, 2015 alcohols, stilbenes, tocopherols, tocotrienols), ascorbic MATERIALS AND METHODS acid and carotenoids which have been reported to show good antioxidant activity [6]. The higher total phenolics Materials: Carbon tetrachloride (CCl4 ), casein, vitamins, content of plants extracts resulted in higher antioxidant minerals, cellulose and choline chloride were purchased activity [7]. from El-Gomhoreya Company, Cairo, Egypt. Fifty five male Clove (Eugenia caryophyllata) and cardamom albino rats (Sprague Dawley Strain) were obtained from ( subulatum) are among the widely used spices. Helwan farm. Clove (Eugenia caryophyllata), cardamom Clove is used to help digestion, prevent vomiting in ( cardmomum) and anise (Pimpinella anisum) pregnancy and has inhibitory effect on histamine were purchased from local market, Cairo Egypt. production [8]. Cardamom has antispasmodic action. Also clove was classified as a source for power Methods: The Biological Assay: Fifty five male albino rats antioxidant activity, whereas, cardamom had a medium (200-210g) were kept in individual stainless steel cages level antioxidant. In addition to its effectiveness in under hygienic conditions and fed one week on basal diet reducing LDL susceptibility to oxidation [9, 10, 11]. It is for adaptation in ad libitum. The basal diet in the evident that 61% of clove is carbohydrates, 20% fat and preliminary experiment consists of 14% casein (protein = the rest contributed by secondary metabolites, vitamins 80%), corn oil 4%, cellulose 5%, vitamin mixture 1%, and minerals. are an excellent source of mixture 3.5%, choline chloride 0.2% and the remainder is manganese, a very good source of dietary fibre, vitamin C, corn starch [22]. Vitamin composition of diets prepared vitamin K and ù-3 fatty acids and a good source of according to A.O.A.C. [23]. After a period of adaptation calcium and magnesium. The major component of the on basal diet (one week), the rats (n=55) were divided into volatile oil is a phenol, namely eugenol [12]. Clove has eleven groups, the first and second groups fed on basal diet as a control negative and positive groups. The third, been reported to possess a potent antioxidant activity in fourth and fifth groups were fed on basal diet containing vitro [13], which reduces the oxidative stress in (2%, 4% and 6% cardamom, respectively), the sixth, the body [14]. Many investigators demonstrated the seventh and eighth groups were fed on basal diet hepatoprotective properties of clove against chemical containing (2%, 4% and 6% clove, respectively), the stress [15]. Treatment with clove and cardamom ninth, tenth and eleventh groups were fed on basal diet effectively decreased liver enzyme levels in the serum. containing (2%, 4% and 6% anise, respectively). On the 27 This can be attributed to the presence of antioxidant in day of the experiment, all animal except the negative clove and cardamom which contain phenolic compounds control group was administered subcutaneous injection that can act by scavenging free radicals [16]. 20% CCl4 in liquid paraffin oil at a dose 5 ml/kg body Anise (Pimpinella anisum) is belongs to the weight to induce hepatotoxicity in rats [24]. During the Umbelliferae family and grows in the Southern and experimental period (28 days), the diets consumed and northwest and countries such as Egypt, Turkey and body weights were recorded twice weekly. Greece [17]. The seeds of P. anisum contain 1.5-6% At the end of the experiment period (28 day), the , 10-20% fixed oil and 18% protein. The main animals were fasted overnight, then the rats were constituents of the essential oil are 90% anethole, anaesthetized and sacrificed and blood samples were 2-4% gammahimachalene, <1% p-anisaldehyde, collected from the aorta. The blood samples were 0.9-1.5% methylchavicol, 3% cis-pseudoisoeugenyl centrifuged and serum was separated to estimate some 2- methylbutyrate and 1.3% trans-pseudoisoeugenyl biochemical parameters, i.e. Total lipid [25], cholesterol 2-methylbutyrate [18]. The essential oil of P. anisum was [26], triglycerides [27], high density lipoprotein- not found effective against carbon tetrachloride-induced cholesterol HDL-c [28], low and very low density acute hepatotoxicity in rats [19]. Hypoglycemic effect of lipoprotein-cholesterol LDL-c and VLDL-c [29], uric acid the essential oil of P. anisum has been reported by Ceylan [30], urea nitrogen [31], creatinine [32], glucose [33], et al. [20]. Diethyl ether extract of anise seed could aspartate amino transferase (AST) and alanine amino ameliorate carbon tetrachloride (CCl4 )-induced liver injury transferase (ALT) [34] and alkaline phosphatase (ALP) [21]. Therefore, the present work was conducted to study [35]. Liver and kidney were separated from each rat and the effect of some levels of clove, cardamom and anise on weighted to calculate organs to body weight %. The data the nutritional and biochemical evaluation of rats obtained was analyzed statistically for standard deviation suffering from hepatotoxicity. and one way ANOVA test [36].

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RESULTS AND DISCUSSION groups. The data in this table revealed that, gradually decrease in BWG% with increasing the levels of Effect of Some Levels of Cardamom, Clove and Anise cardamom, clove and anise. The highest decrease in on Feed Intake, Body Weight Gain% and Some Organs BWG% recorded for the groups treated with cardamom (4 Weight/Body Weight% of Rats Suffering from and 6g/100g diet). These groups showed significant Hepatotoxicity. decrease p<0.05 in BWG%, as compared to other treated The effect of different levels from cardamom, clove groups. The mean values of liver and kidney weights / and anise on feed intake, body weight gain% and (liver body weights% increased significantly (P=0.05) of and kidney) weights / body weight % of rats suffering the positive control group (CCl4 treated groups), as from hepatotoxicity presented in Table 1. The mean value compared to the negative control group (3.489 ± 0.099 and ± SD of feed intake in the negative control group recorded 0.848 ± 0.041 vs. 2.490 ± 0.141 and 0.603 ± 0.038), 17.00± 0.816 g/day for each rat, while the mean values of respectively. All treated groups with the three levels of feed intake in the positive control group which suffering cardamom, clove and anise showed significant decrease from hepatotoxicity recorded 16.250± 0.957g/day for each (p=0.05) in liver and kidney weights/body weights%, as rat. The results in Table 1 showed non-significant compared to the positive control group. Gradually changes in feed intake between the negative and positive decrease in the mean values of liver and kidney weights control groups. Feed intake of all treated groups was observed with increase the levels of cardamom, clove decreased gradually with increasing the levels of and anise in hepatotoxic groups. The best results in liver cardamom, clove and anise. and kidney weights / body weights % observed in The mean values of feed intake of rats groups hepatotoxic group treated with diet containing received diets containing (4% and 6% cardamom) and (6g clove/100g diet). (2% and 6% anise) decreased significantly p<0.05, The oral administration of a low dose of carbon while other treated groups showed non-significant tetrachloride to rats reduced the body weight and food difference, as compared to the positive control group. intake at 24 h with a minimal effect on plasma alanine The highest decrease in the mean value of feed intake aminotransferase activity [37]. Rats with or without food recorded for the group which treated with 6% cardamom. restriction, a low dose of carbon tetrachloride (1 ml/kg of The mean value of BWG% between the negative and a1:1 solution with olive oil) treatment induced hepatitis positive control group showed non-significant difference and reduced the body weight gain. In contrast, carbon at (P<0.05) (36.500± 2.645vs. 35.00± 3.162), respectively. tetrachloride treatment did not induce hepatitis in rats Treating groups with the three levels (2, 4 and 6%) without food restriction, but the body weight was cardamom, clove and anise led to significant decrease in decreased. In these rats, the loss of body weight was BWG%, as compared to the negative and positive control accompanied by a decrease in food intake [38].

Table 1: Effect of some levels of cardamom, clove and anise on nutritional parameters and some organs weight/body weight % of rats suffering from hepatotoxicity. Parameters Organs weight/body weight % ------Groups Feed intake (g/day) Body weight gain % (BWG %) Liver Kidney Control (-) 17.00 a ± 0.816 36.500 a ± 2.645 2.490 f ± 0.141 0.603 e ± 0.038 Control (+) 16.250 abc ± 0.957 35.00 a ± 3.162 3.489 a ± 0.099 0.848 a ± 0.041 Cardamom (2g/100g diet) 15.500 cde ± 0.707 18.500 c ± 1.732 3.016 b ± 0.117 0.715 b c ± 0.038 Cardamom (4g/100g diet) 14.500 ef ± 0.408 15.750 d ± 1.707 2.710 d ± 0.118 0.726 b ± 0.017 Cardamom (6g/100g diet) 13.875 f ± 0.478 14.500 d ± 1.00 2.790 cd ± 0.114 0.693 bcd ± 0.018 Clove (2g/100g diet) 16.250 abc ± 0.500 21.00 c ± 1.414 2.913 bc ± 0.107 0.679 cd ± 0.021 Clove (4g/100g diet) 16.750 ab ± 0.512 20.250 c ± 0.957 2.663 de ± 0.043 0.656 d ± 0.018 Clove (6g/100g diet) 15.500 cde ± 0.577 18.750 c ± 1.700 2.525 ef ± 0.071 0.606 e ± 0.017 Anise (2g/100g diet) 15.00 de ± 0.817 23.750 b ± 0.957 2.920 bc ± 0.114 0.721 bc ± 0.034 Anise (4g/100g diet) 15.750 bcd ± 0.948 20.500 c ± 1.291 2.743 d ± 0.079 0.696 bcd ± 0.015 Anise (6g/100g diet) 15.00 de ± 0.816 19.00 c ± 1.825 2.664 de ± 0.052 0.678 cd ± 0.016 All results are expressed as mean ± SD. Values in each column which have different letters are significant different (p<0.05).

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Table 2: Effect of some levels of cardamom, clove and anise on liver enzymes of rats suffering from hepatotoxicity. Parameters AST ALT ALP ------Groups u/l Control (-) 50.305 g ± 3.679 15.137 g ± 1.614 84.250 I ± 4.425 Control (+) 184.220a ± 4.451 88.517 a ± 3.072 202.00 a ± 9.092 Cardamom (2g/100g diet) 158.182 bc ± 4.728 74.260 b ± 2.721 175.750 b ± 4.349 Cardamom (4g/100g diet) 148.540 de ± 4.009 69.542 c ± 1.974 163.750 cd ± 4.787 Cardamom (6g/100g diet) 144.880 e ± 4.919 64.320 de ± 1.384 150.250 fg ± 4.113 Clove (2g/100g diet) 152.772 cd ± 5.350 67.935 cd ± 4.556 168.750 bc ± 6.291 Clove (4g/100g diet) 145.852 de ± 4.061 65.347 de ± 0.680 155.00 e f ± 4.082 Clove (6g/100g diet) 137.875 f ± 4.191 51.232 f ± 1.099 140.250 h ± 4.113 Anise (2g/100g diet) 160. 717 b ± 4.317 75.852 b ± 1.689 172.750 b ± 6.849 Anise (4g/100g diet) 151.297 de ± 4.686 66.515 cd ± 2.938 158.750 de ± 3.685 Anise (6g/100g diet) 145.122 e ± 4.477 62.042 e ± 2.148 143.00 gh ± 6.164 AST: Aspartate Amine Transaminase. ALT: Alanine Amine Transaminase ALP: Alkaline Phosphatase. All results are expressed as mean ± SD. Values in each column which have different letters are significant different (p<0.05).

Administration of CCl4 (0.5 ml/kg, s.c. in olive oil) conjugated bilirubin, ALP, gamma-GT and total iron levels significantly increased relative kidney weight (g per were significantly higher in CCl4 -treated rats than in the 100 g body weight) compared to control (p<0.01) [39]. controls, while urea, total protein and albumin levels were

The increase in relative weight of liver and heart in CCl4 significantly lower [43]. The activities of serum marker induced liver injury [40]. The reason of reducing body enzymes glutamate oxaloacetate transminase (GOT), weight with the higher level of anise seed glutamate pyruvate transaminase (GPT) and alkaline supplementation (1.5 g/kg diet) could be affected phosphatase (ALP) were elevated significantly in carbon negatively digestive system [41]. tetrachloride induced rats [44]. Effect of Some Levels of Cardamom, Clove and Anise Feeding rats on diets containing (2%, 4% and 6%) on Liver Enzymes of Rats Suffering from Hepatotoxicity. cardamom, clove and anise caused significant decrease The data presented in Table 2 showed the protective p<0.05 in AST, ALT and ALP, as compared to the positive effect of the three levels (2, 4 and 6%) from cardamom, control group. On the other hand the mean values of AST, clove and anise on Aspartate Amine Transferase (AST), ALT and ALP enzymes decreased gradually with Alanine Amine Transferase (ALT) and Alkaline increasing the levels of cardamom, clove and anise. phosphatase (ALP) U/L of rats suffering hepatotoxicity. The high level of clove is more effect in reducing the Liver enzymes including (AST, ALT and ALP) in the concentration of AST, ALT and ALP, than that of the positive control group fed on basal diet increased anise and cardamom, respectively. Treatments of significantly (p<0.05), as compared to the negative control hepatotoxicity groups with 6% clove, anise and cardamom group fed on basal diet. AST, ALT and ALP increased in decreased AST enzyme by about (25.157%, 21.223% and the positive control group by about (266.206%, 484.772% 21.354%), ALT by about (42.121%, 29.909% and 27.335%) and 139.762%), than that of the negative control group, and ALP by (30.569%, 29.207 and 25.618%), respectively, respectively. In this respect, Singh et al. [42] reported than that of the positive control group. From these that, liver damage induced in rats by carbon tetrachloride results, it could be concluded that, treating rats which was obvious macroscopically as well as microscopically suffer from hepatotoxicity with clove, anise and cardamom in stained sections. Level of aspartate aminotransferase improved the liver enzymes than that of non-treated rats. (AST), alanine aminotransferase (ALT) and gamma Clove administration has tendency to retrieve levels glutamyl trans peptidase (gamma-GT) were also of AST, ALT, urea and lipid profiles in serum, liver and significantly raised. Adenosine and inosine effectively kidneys towards near normal values in hyperlipidemic rats countered the damage when these were given before and [45]. Treatment with clove and cardamom effectively during the period during which CCl4 produces the decreased liver enzyme levels in the serum. This can be typical damage. Injection rats subcutaneously with CCl4 attributed to the presence of antioxidant in clove and (0.5 ml/kg in olive oil), serum AST, ALT, total and cardamom which contain phenolic compounds that can

857 World Appl. Sci. J., 33 (6): 854-865, 2015 act by scavenging free radicals [16]. Serum AST, ALT, The effect of different levels from cardamom, clove ALP, total bilirubin were significantly lower (p < 0.05) after and anise on total lipids, total cholesterol (TC), five weeks intake of 2% clove in iron overloaded rats [46]. triglycerides (TG), high-density lipoprotein-cholesterol Administration of 2% cardamom in rats significantly (HDL-c), low and very low density lipoprotein-cholesterol reduced (p<0.05) liver enzymes specifically for AST [47]. (LDL-c and VLDL-c) of rats suffering from hepatotoxicity Aniseed could be used at 30 g/Kg level in quail diets for is presented in (Tables 3 and 4). The data in Table 3 an increased antioxidant activity with glutathion GSH and revealed that, total lipid, total cholesterol and triglycerides decreased malondialdehyde MDA levels [48]. P. anisum increased significantly p<0.05 in CCl4 group (the control oil protected rats from aspartame-induced liver positive group), as compared to the healthy group histopathological changes [49]. Diethyl ether extract of (control negative group). Carbon tetrachloride (CCl4 ) anise seed could ameliorate carbon tetrachloride induced hepatotoxicity in rats increased the levels of

(CCl4 )-induced liver injury [21]. Essential oils of lipids cholesterol, triglycerides and free fatty acids in Pimpinella anisum (Anise) or Foeniculum vulgare plasma and tissues (liver, kidney, heart and brain) [55].

() possessed a hepatoprotective activity against CCl4 increased the synthesis of fatty acids and hepatotoxicity induced by CCL4 induced fibrosis model in triglycerides and the rate of lipid esterification. rats [50]. Consumption of aspartame-induced hepatorenal Cholesterol and phospholipids synthesis from acetate toxicity. Using an antioxidant such as P. anisum was also increased. This could be due to the transport of decreased the toxicity of aspartame [51]. Anise could have acetate into the liver cell, resulting in increased substrate a radical scavenging effect, inhibiting H22 O -chelating (acetate) availability [56]. Injection rats with carbon and Fe2+-chelating activity by more than 70% [52]. tetrachloride (3.2g/kg /72h) for one month increased The polyphenols present in the anise seeds could donate significantly the serum and tissue lipid profile [57]. electrons and react with free radicals to convert them into The mean values of total lipids, cholesterol and more stable products and terminate the free radical chain triglycerides decreased significantly in all treated groups reaction, whereas other compounds in the oil act as p<0.05, as compared to the positive control group. chainbreaking agents in lipid peroxidation [53]. P. anisum The data in this table showed non-significant changes in increases vitamin C and E levels, which may lead to serum lipids, cholesterol and triglycerides between the decreased oxidative stress as both vitamins are hepatotoxic groups treated with the low levels (2g/100g scavengers of the toxic free radicals generated with cardamom and anise), while treating hepatotoxic group aspartame [54]. with diet containing 2g clove/100g diet showed significant Effect of Some Levels of Cardamom, Clove and Anise decrease p<0.05, as compared to the groups which treated on Lipid Profile of Rats Suffering from Hepatotoxicity. with the low levels (2g/100g) of cardamom and anise.

Table 3: Effect of some levels of cardamom, clove and anise on total lipids, cholesterol and triglycerides of rats suffering from hepatotoxicity. Parameters Total lipid Cholesterol Triglycerides ------Groups mg/dl Control (-) 409.00 f ± 8.406 76.890 h ± 4.513 38.357 I ± 2.123 Control (+) 539.750 a ± 10.436 181.405 a ± 4.602 90.765 a ± 3.300 Cardamom (2g/100g diet) 491.250 b ± 8.301 164.272 b ± 4.071 76.567 b ± 3.294 Cardamom (4g/100g diet) 466.250 c ± 4.787 149.752 d ± 5.652 65.765 d ± 4.197 Cardamom (6g/100g diet) 445.500 d ± 5.259 139.955 e f ± 3.092 56.045 f g ± 3.765 Clove (2g/100g diet) 473.750 c ± 4.787 158.010 c ± 5.124 71.347 c ± 2.763 Clove (4g/100g diet) 454.00 d ± 5.228 139.045 ef ± 4.185 58.407 e f ± 1.446 Clove (6g/100g diet) 419.500 e ± 8.812 129.047 g ± 3.040 51.017 h ± 2.451 Anise (2g/100g diet) 499.500 b ± 7.047 160.395 bc ± 3.769 74.105 b c ± 1.804 Anise (4g/100g diet) 473.250 c ± 2.638 144.192 de ± 3.625 61.735 e ± 1.208 Anise (6g/100g diet) 453.250 d ± 5.560 134.530 fg ± 0.571 53.915 gh ± 2.020 All results are expressed as mean ± SD. Values in each column which have different letters are significant different (p<0.05).

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Table 4: Effect of some levels of cardamom, clove and anise on serum lipoprotein-cholesterol of rats suffering from hepatotoxicity. Parameters HDL-c LDL-c VLDL-c ------Groups mg/dl Control (-) 45.432 a ± 2.186 23.786 I ± 1.912 7.671 I ± 0.424 Control (+) 20.922 g ± 3.177 142.329 a ± 3.978 18.153 a ± 0.660 Cardamom (2g/100g diet) 26.745 f ± 1.929 122.214 b ± 2.060 15.313 b ± 0.658 Cardamom (4g/100g diet) 30.220 e ± 2.033 106.379 d ± 4.062 13.153 d ± 0.839 Cardamom (6g/100g diet) 36.262 bc ± 0.559 92.483 fg ± 3.174 11.209 f g ± 0.753 Clove (2g/100g diet) 28.457 ef ± 1.957 115.283 c ± 3.351 14.269 c ± 0.552 Clove (4g/100g diet) 32.977 d ± 2.054 94.386 f ± 2.923 11.681 ef ± 0.289 Clove (6g/100g diet) 38.537 b ± 1.223 80.306 h ± 2.217 10.203 h ± 0.490 Anise (2g/100g diet) 26.962 f ± 1.476 118.611 bc ± 2.383 14.821 bc ± 0.360 Anise (4g/100g diet) 33.067 d ± 1.270 98.778 e ± 2.656 12.347 e ± 0.241 Anise (6g/100g diet) 34.882 cd ± 0.838 88.864 g ± 0.917 10.738 g h ± 0.404 HDL-c: High density lipoprotein-cholesterol. LDL-c: Low density lipoprotein-cholesterol VLDL-c: Very low density lipoprotein-cholesterol. All results are expressed as mean ± SD. Values in each column which have different letters are significant different (p<0.05).

The data in Table 3 also showed that, treating rats which hepatotoxicity with diets containing (2%, 4% and 6%) were suffering from hepatotoxicity with diet containing cardamom, clove or anise led to significant decrease in (6g clove/100g diet) decreased the mean values of total VLDL-c, as compared to the positive control group. lipid, cholesterol and triglycerides, as compared to the rats Treating rats with diets containing 6% (clove, anise and fed on the same level from cardamom or anise. cardamom) achieved the best results in VLDL-c, Treating rats which suffering from hepatotoxicity with respectively. From these results in Tables 3 and 4, it could (6% clove) decreased the mean values of total lipids, be concluded that, treating rats which suffer from cholesterol and triglycerides by about (22.278%, 28.862% hepatotoxicity with clove, anise and cardamom and 43.792%), respectively. improved the lipid fractions than that of non-treated rats. Data in Table 4 indicated that, the positive control The highest improvement recorded for the groups treated group (hepatotoxic group) showed significant increase with the different levels of clove. (p<0.05) in serum LDL-c and VLDL-c, while HDL-c Clove administration has tendency to retrieve levels decreased, as compared to the rats fed on basal diet of AST, ALT, urea and lipid profiles in serum, liver and (control negative group). High density lipoprotein- kidneys towards near normal values in hyperlipidemic rats cholesterol increased gradually with increasing the levels [45]. Dietary supplementation with 2% , 2% clove of cardamom or clove or anise in the diets. High density and 2% cardamom caused significant reductions in lipoprotein in all treated groups increased, especially the serum total cholesterol, triacylglycerol, LDL-C and groups fed on diet containing high level from clove VLDL-C, on the other hand a significant increase (p <0.05) followed by the groups fed on diet containing high level was observed in serum HDL-cholesterol level in clove-fed of cardamom and anise, respectively. Treating rats which rats [46]. Administration of cardamom in a dose of were suffer from hepatotoxicity with (6%) cardamom, 1.5 g twice daily in stage 1 hypertensive individuals clove and anise increased HDL-c by about (73.319%, significantly decreased total cholesterol (19%), 84.193% and 66.724%), respectively. Low density triglycerides (15%), VLDL-C (15%) and LDL-C (25%) lipoprotein decreased in all treated groups with low, levels at the end of 3 months of cardamom administration medium and high levels from cardamom, clove and anise. [58]. The clove extract-treated group had a 68% and 80% Low density lipoprotein-cholesterol decreased gradually decrease in serum cholesterol and TG levels, respectively with increasing the levels of cardamom, clove and anise. in vitro and in vivo using hypercholesterolemic zebra fish Feeding rats on diet containing 6% clove achieved the [59]. The hypolipidemic effect of food spices best results in LDL-c, this treatment recorded significant mixture on fructose-fed insulin resistant rats. Male Wistar decrease in this parameter, as compared to other treated rats received a daily diet containing either 60% fructose or groups. Treating rats which were suffer from 60% starch. They were administered with the spices

859 World Appl. Sci. J., 33 (6): 854-865, 2015 mixture (Dry , Cardamom, , Clove, , The results of the present study showed that serum total , , , and Mace) at cholesterol concentration was significantly reduced when three different doses (10mg, 30mg or 50mg/day/rat) orally fed rats on diets containing different levels of anise seed, 15 days later. At the end of 45 days of the experimental a finding that is in agreement with those obtained by period fructose-fed rats displayed elevated plasma Ali et al. [65]. Anise seed in broiler diets did not affect glucose and insulin levels and dyslipidemia which serum total cholesterol concentration [41]. The cholesterol included elevated levels of cholesterol, triglycerides, reducing effect may be attributed mainly to the effect of free fatty acids, reduced high density lipoprotein the trans-anethole. Phytoestrogen consumption can cholesterol and increased very low density lipoprotein regulate serum cholesterol levels in the human and cholesterol. Alterations in tissue lipid levels were also animals [66, 67]. Dietary anise decreased the levels of observed. Simultaneous treatment with spices mixture serum triglycerides and total lipids [65]. Cholesterol along with fructose diet resulted in the normalization of concentration in the serum tended to decrease with the plasma glucose and insulin levels and restoration of lipid addition of anise to the diet [67]. levels in plasma and tissues. The insulin potentiating Effect of Some Levels of Cardamom, Clove and Anise action of the active principles in these spices may on Serum glucose and Kidney Functions of Rats Suffering contribute to the hypolipidemic effect of spices mixture in from Hepatotoxicity high fructose-fed rats [60]. The effect of some levels from cardamom, clove and Treatment with clove oil significantly improved these anise on serum glucose, uric acid, urea nitrogen and hyperlipidemia conditions. Clove oil might lower the creatinine (mg/dl) of rats suffering from hepatotoxicity plasma free fatty acid, triglycerides and cholesterol levels is presented in Table 5. Injected rats with CCl4 to induce and simultaneously reduced the hepatic fatty acid hepatotoxicity, increased serum glucose, uric acid, urea oxidation. These changes might be attributed to a nitrogen and creatinine significantly (p<0.05), as suppression in the hepatic fatty acid synthase, compared to the negative control group. Serum glucose glucose-6-phosphate dehydrogenase and also it may increased in the positive control group by about have been partly due to the decreased hepatic-3-hydroxyl- 107.937%, than that of the negative control group, on the 3-methyl glutaryl Co-enzyme (HMG CoA) reducatse and other hand, serum uric acid, urea nitrogen and creatinine acyl CoA: cholesterol acyl transferase (ACAT) activities increased in the positive control group by about [45, 61, 62], the researchers reported that clove oil 129.958%, 236.089% and 316.850%, than that of the improved the levels of cholesterol, T.G. and negative control group. Results of biochemical studies of phospholipids in serum of hyperlipidemic rats. blood samples of carbon tetrachloride treated rats showed Cholesterol lowering effect of clove and cardamom significant increase in the levels of serum glucose [68]. was reported by El-Segay [15], who showed that ethanol CCl44 treatment (5 ml/kg body wt., i.p. CCl :olive oil, 1:9) feeding caused elevation of serum liver enzymes and significantly increased the level of urine creatinine, serum total lipid, total cholesterol and triglyceride levels. protein, nitrite, urobilinogen, red blood cells (RBCs), Also, there was significant increase in lipid peroxidation leucocytes count and levels of blood urea nitrogen (BUN) product, malonaldehyde (MDA) and decrease in [69]. All treated groups with tested diets containing the antioxidant enzyme, trace element levels in liver three levels of (cardamom, clove or anise) showed homogenate. On the other hand, the hepatoprotective significant decrease in serum glucose, as compared to the effect of cardamom and clove was reflected by the positive control group. Serum glucose decreased significantly lower level of liver enzymes and serum lipid gradually with increasing the levels of cardamom, clove or profile in rats pretreated with their extract before ethanol. anise in the diets. Treating hepatotoxic groups with diets Clove was classified by Sharma et al. [10] as a source for containing 6% (clove or anise) recorded the best results powerful antioxidant activity, whereas, cardamom had a in serum glucose, as compared to other treated groups. medium level antioxidant power, in addition to its Dietary supplementation with cloves significantly effectiveness in reducing LDL susceptibility to oxidation. reduced blood sugar and lipid peroxidation in The antioxidant activity of clove and cardamom could be streptozotocin-induced diabetic rats by restoring the attributed to its phytochemical contents which increases antioxidant enzyme levels [70]. After 8 weeks, the diabetic the amount or increase the activity of antioxidant rats fed on spices (cinnamon, clove and ginger) or their enzymes, or due to their trace element contents which are essential oils significantly decreased levels of blood required for the antioxidant enzyme activity [63, 64]. glucose and significantly increased insulin level [71].

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Table 5: Effect of some levels of cardamom, clove and anise on serum glucose and kidney functions of rats suffering from hepatotoxicity. Parameters Glucose Uric acid Urea Nitrogen Creatinine ------Groups mg/dl Control (-) 75.377 g ± 3.924 1.462 g ± 0.056 23.040 h ± 3.290 0.635 g ± 0.069 Control (+) 156.737 a ± 2.691 3.362 a ± 0.168 77.435 a ± 2.558 2.647 a ± 0.068 Cardamom (2g/100g diet) 143.602 b ± 2.485 2.982 b ± 0.158 69.555 b ± 3.404 2.300 b ± 0.090 Cardamom (4g/100g diet) 128.087 d ± 4.608 2.507 d ± 0.201 62.737 cd ± 7.319 2.056 c ± 0.053 Cardamom (6g/100g diet) 117.242 e ± 4.935 2.151 ef ± 0.142 54.100 ef ± 4.037 1.784 e ± 0.031 Clove (2g/100g diet) 135.402 c ± 4.455 2.597 cd ± 0.179 65.552 bc ± 3.142 2.113 c ± 0.085 Clove (4g/100g diet) 116.965 e ± 4.404 2.167 ef ± 0.117 56.492 ef ± 6.009 1.903 d ± 0.076 Clove (6g/100g diet) 105.177 f ± 4.163 1.935 f ± 0.119 47.162 g ± 2.841 1.661 f ± 0.059 Anise (2g/100g diet) 139.797 bc ± 4.178 2.755 c ± 0.097 68.667 bc ± 1.845 2.248 b ± 0.141 Anise (4g/100g diet) 121.185 e ± 3.159 2.192 e ± 0.102 59.417 de ± 4.398 1.972 cd ± 0.053 Anise (6g/100g diet) 110.657 f ± 4.054 2.060 ef ± 0.236 51.492 f g ± 2.007 1.704 ef ± 0.005 All results are expressed as mean ± SD. Values in each column which have different letters are significant different (p<0.05).

The cardamom leaves contain 129.6±6.9 mg/g flavonoids in attenuation of metacide pesticide caused oxidative and vitamin C 19.22±1.1mg/g [72]. It has been reported damage, disturbance and injury induced in liver, that flavonoids has antioxidant [73] and antidiabetic [74]. kidney and thyroid hormone function [78]. Eugenol Non-glycosylase of flavonoids clarify reduction of ameliorates Gentamicin GM-induced nephrotoxicity and absorption activity of sodium-dependent glucose either oxidative damage by scavenging oxygen free radicals, in vitro or in vivo [75]. decreasing lipid peroxidation and improving intracellular All treated hepatotoxic groups with the three levels antioxidant defense [79, 80]. (2%, 4% and 6%) of cardamom, clove and anise showed significant decrease (P<0.05) in all kidney functions REFERENCES parameters, as compared to the positive control group. The mean values of serum uric acid, urea nitrogen and 1. Athar, M., Z.S. Zakir Hussain and N. Hassan, 1997. creatinine decreased gradually with increasing the levels Drug Metabolizing Enzymes in the Liver. In: Rana, of cardamom, clove and anise. The highest % of clove or S.V.S. and Taketa, K., editors. Liver and anise in the diets recorded the best results in kidney Environmental Xenobiotics. New Delhi: Narosa functions, these treatments decreased the mean values of Publishing House, pp: 65-72. serum uric acid, urea nitrogen and creatinine by about 2. Ulicna, O., M. Greksák, O. Vancová, L. Zlatos, (42.444%, 39.094% and 37.249%) and (38.726%, 33.502% S. Galbavý, P. Bozek and M. Nakano, 2003. and 35.625%), respectively. Treatment of diabetic rats with Hepatoprotective Effect of Rooibos (Aspalathus

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