Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess Home Economic Dept., Fac. of Specific Education, Ain-shams University ABSTRACT out is an inflammatory joint disorder characterized by hyperuricaemia and precipitation of monosodium urate crystals in the joints. This G study aimed to discover the beneficial effects of feeding or / and ginger, as a powder form, on the consequence symptoms of gout on induced hyperuricemic rats. Forty nine male albino rats weighing 192 ±23g were divided into 7 equal groups; negative control group fed on standard diet only, while the other 6 experimental groups were injected orally with ethanol (1.8g per kilogram of body weight) every 24 hour for eight days to induce , after confirmation they fed on standard diet only (positive control) or with adding 1% & 2% ginger, 1% & 2% cinnamon and mixture of 1% ginger + 1% cinnamon of total diet weight for continued four weeks after adaptation period. Serum , urea and creatinine, serum liver (AST, ALT, and ALP) activities, total protein, serum albumin and globulin levels were determined. Results revealed that supplementations with ginger, cinnamon or their mixture for hyperuricemic rats diets; declined the feed efficiency ratios, while increased relative weight of liver and kidneys significantly (p<0.05) ameliorated proportionally with the level of adding, also increments of uric acid, urea and creatinine levels were decreased significantly, furthermore decreased the raised serum levels of ALT, AST & ALP enzymes’ activities and ameliorated significantly the documented decrements in the levels of serum total proteins and albumin comparing with positive control group. Histopathological kidneys’ investigation revealed that higher supplementations with 2% ginger, cinnamon or their mixture groups modulate all undesirable changes recorded in kidneys of positive control group. These outcomes could mention that using ginger and cinnamon may improve kidney functions, liver enzymes and protein fractions, especially the mixture of them which was the most beneficial effects recorded; it could be used as hypouricemic agent and adjuvant treatment for gout disease.

Key words: Ginger, Cinnamon, Nutrition, Hyperuricemia, Rats, Liver enzymes, Kidney functions and protein fractions.

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess INTRODUCTION acid are strong reducing Uric acid is a final agents (electron donors) and enzymatic product in the potent antioxidants. In degradation of humans, over half the , and it has the antioxidant capacity of blood ability to scavenge oxygen plasma comes from uric acid. radicals and protect the About 70% of daily uric acid erythrocyte membrane from disposal occurs via the lipid oxidation. Uric acid is kidneys and in 5-25% of produced by oxidase humans impaired renal from xanthine and excretion leads to , which in turn hyperuricemia (Vitart et al., are produced from purine. 2008). Uric acid is more toxic to tissues than either xanthine or Hyperuricemia is the hypoxanthine. A xanthine major and primary risk factor oxidase inhibitor is any of symptomatic gout, the substance that inhibits the clinical significance of which activity of xanthine oxidase, has been identified as the an involved in purine development of various co- metabolism. In humans, morbidities, including gout inhibition of xanthine oxidase metabolic syndrome, coronary reduces the production of uric artery disease and type-2 acid (Pacher et al., 2006). diabetes, despite its major antioxidant property In most other mammals, (Changgui et al., 2013). the enzyme uricase further There are many factors that oxidizes uric acid to allantoin. contribute to hyperuricemia The loss of uricase in higher including obesity, insulin primates parallels the similar resistance, loss of the ability to synthesize consumption, diuretic use, ascorbic acid (Proctor, 1970). hypertension, renal Both uric acid and ascorbic insufficiency and genetic

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

makeup… etc. Of these, They are paradoxically alcohol (ethanol) is the most opposing under different important, which enhances experimental conditions. Uric acid is a powerful signaling degradation and increases molecule that can affect lactic acid level in blood, intracellular signal leading to hyperuricemia transduction, leading to (Tetsuya et al., 2005). oxidant production via nicotinamide adenine Elevated serum uric acid dinucleotide phosphate (hyperuricemia) can result (NADPH) oxidase and also from high intake of expression of pro- purine-rich foods or high inflammatory mediators. fructose intake (Tausche et al., 2006). Excess serum Medicinal are accumulation of uric acid, important for pharmacological which could lead to a type of research and arthritis known as “Gout” is development, one fifth of all nine times more common in the plants found in India are men than in women (Heinig used for medicinal purpose. and Johnson, 2006). It Out of these the bark of predominantly attacks males “Cinnamon” is widely used as after puberty, with a peak age a spice due to its distinct odor of 75, while in women gout of essential oils. Main attacks usually after chemical constituents are menopause. Also, Yuri et al., Cinnamic acid, (2011) reported that biological , Euginol, and effects of uric acid, generated essential oils (Vaibhavi et al., in the human body either from 2010). Cinnamaldehyde may food or resulting from the be a potential lead compound purine degradation pathway for developing the via xanthine oxidoreductase, pharmaceutic of anti- are extremely pleiotropic.

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess hyperuricemia agent (Wang et number of diseases; including al., 2008). headache, cold, arthritis, renal function, and reduces serum Polyphenols, which are creatinine, urea, and Blood among the natural dietary urea nitrogen (BUN). The antioxidants found in mechanisms of these cinnamon, have been shown to renoprotective effects may reduce oxidative stress in a involve both oxidative stress dose-dependent manner via reduction and significant 6- the inhibition of 5- gingerol antioxidant effects lipoxygenase. Specific too (Mahmoud et al., 2012). antioxidant phytochemicals that have been identified in Therefore, the present cinnamon include epicatechin, study was carried out to camphene, eugenol, gamma- investigate the effects of terpinene, phenol, salicylic feeding two doses of acid and tannins. Today, cinnamon, ginger or their natural antioxidants are the mixture supplementations on focus of considerable attention induced hyperuricemia in and efforts are ongoing for the albino rats. replacement of synthetic ones. In addition, these natural MATERIALS & METHODS antioxidants can be formulated Materials as functional foods and can Cinnamon and ginger help prevent oxidative damage powders were obtained from from occurring in the body the Agriculture Seeds, Herbs (Hamidpour et al., 2015). and Medicinal Plants Company, Cairo, Egypt, and Zingiber officinal used individually or combined Roscoe (Ginger) is an in rats’ feeding as indispensable component of hyperuricemic treatments. curry, belongs to the Basal diet used was prepared Zingiberaceae family. Ginger according to Jerome et al., has been used to treat a

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

(2002), while the composition (42 rats) administered orally of minerals mixture used was the ethanol (1.8 g per kilogram according to Hegested et al., of body weight) every 24 (1941) and the vitamins hours for eight days to induce mixture used was that of hyperuricemia according to Campbell, (1963). Ethanol Faller and Fox, (1982). has been used to induce Ethanol, 50%, increases urate hyperuricemia according to synthesis by enhancing the Faller and Fox, (1982), which turnover of adenine obtained as liquid chemical . Hyperuricemia from “Elgomhoria” Company, was confirmed after orally Cairo, Egypt. swallowed, and then rats were divided into six groups Forty nine male albino (7rats/group) and fed on: basal rats, Sprague Dawley strain, of diet only (Positive control) or mean body weight 192 ±23g with additives; 1% cinnamon were obtained from the or ginger or 2% cinnamon or laboratory animal house of ginger or combination of them Ophthalmic Research equally as 2% of total diet Institute, Giza, Egypt. weight for four continued Animals were acclimatized to weeks. Quantities of laboratory condition before consumed diet and waste were experimental applying and fed recorded daily, also rats’ on basal diet and water ad- weight assessed weekly and libitum. feed efficiency ratio (FER) were calculated according to Methods Chapman et al., (1959). Adapted rats were divided into seven equal Four weeks later, groups; first group (7rats) was blood samples were collected normal rats fed on basal diet from hepatic portal vein and only and served as negative centrifuged for 10 minutes at control. While the remaining 3000 revolutions per minute

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

"r.p.m." to separate the serum assessed according to from fasted rats and kept the reaction described frozen at – 20 oC till analysis by Faulkner and for; King (1976).

• Liver enzymes activity: • Serum Proteins: Total Serum Aspartate protein was estimated Aminotransferase as described by (AST) and serum Sonnenwirth and Alanine Jaret, (1980), while Aminotransferase albumin was (ALT) were determined according determined according to Drupt, (1974). to Reitman and While globulin was Frankel, (1957). calculated according to While Serum Alkaline the equation described Phosphatase (ALP) by Chary and was performed Sharma, (2004); according to the Globulin (mg/dl) = method of Roy, Total protein (mg/dl) – (1970). Albumin (mg/dl).

• Kidney functions: Livers, hearts and kidneys Serum uric acid was were removed and washed determined according with saline solution and dried to the method then weighted for relative described by Barham weight of organs calculation, and Trinder, (1972) then kidneys were kept in and Fossati et al., buffered formalin solution (1980), while urea was (10%) for histopathological determined according examinations according to to Kaplan, (1984), but Drury and Wallington, serum creatinine was (1980).

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

Statistical analysis Regarding to the same Data obtained were table feed efficiency ratio statistically analyzed using (FER) showed that there were computer program of significant decrements for all Statistical Analysis System groups comparing with "SAS". The results were negative control, while expressed as mean ± standard supplementations with ginger deviation "SD" and tested for or cinnamon or their mixture significance using one way for introduced diet declined ANOVA, Duncan test at a more the FERs of the probability "P"<0.05 , hyperuricemic rats, especially according to Armitage and cinnamon and the mixture Berry, (1987). which were significant than ginger. RESULTS & DISCUSSION Data presented in table These results were in (1) shows that body weight agreement with Saravanan et gain (BWG %) of al., (2014) and Shalaby& hyperuricemic (positive Saifan, (2014), who control) group declined about documented that cinnamon 40.6% of negative control one. and ginger extracts exhibited On the other hand, treated anti obesity and hypolipidemic groups received supplemented effects in obese rats. They diet with cinnamon or the elucidated that the possible mixture of it with ginger potential mechanism showed significant decrements underlying the hypolipidemic in BWG% compared with the effect of them could be due to positive and negative control their high contents of groups, while rats received polyphenols (cinnamon) and supplemented diet with both of gingerols and shogaols gingers’ ratios recorded (ginger), which inhibit the insignificant decrements with intestinal absorption of positive control group. cholesterol with subsequent

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess hypocholesterolemic activity. increase metabolic rate Also, cinnamon contains significantly, thus causing choline, which helps the body more calories to be burned metabolize fats, makes up a rather than stored in the body part of healthy cell membranes as fat. and helps drive a number of chemical reactions within cells Data presented in according to Vangalapati et Table (2) showed that oral al., (2012). administration with ethanol 1.8g/kg b.w. every 24 hr. for On the other hand, eight days led to significant Giner and Meguid, (1993) increments (p<0.05) in liver, mentioned that 3% ethanol heart and kidneys weight / solution provided 19 kcal body weight % as compared to /day, which was equivalent to healthy rats. Treatments with about 50% of the daily caloric ginger or cinnamon or their intake of the rats. So that, mixture ameliorated ethanol significantly decreased significantly these increments. food intake, irrespective of the Regarding to relative weight route administered, but this of liver and kidneys, reduction in feed intake did cinnamon was more effective not result in a calorie-to- in this amelioration than calorie compensation. Instead, ginger, which was directly providing 50% of calories as proportional with the level of 3% ethanol via the intragastric adding, while the mixture of route led to a 16% reduction in them was the most feed intake, while only a 9% pronounced amelioration. reduction in feed intake occurred when the 3% ethanol Also, the significant solution was given enlargement documented in intravenously. Also, Klesges positive control group for et al., (1994) found that heart’s relative weight was alcohol also appears to ameliorated significantly (p<0.05) in all treated groups,

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess but ginger was more effective hyperuricemic rats fed on than cinnamon, the mixture of different ratios of ginger or them was the most cinnamon or combination of pronounced amelioration too. them. It is clear that serum As reported by Mathew and levels of uric acid, urea and Abraham, (2006) and Kim et creatinine of positive control al., (2005), ginger and group were raised cinnamon have highly significantly (p<0.05) after antioxidant properties, ethanol treatment comparing therefore they may show with negative control group. significant amelioration for While, all treated groups with the relative weight of enlarged the herbs had decrements in organs. the serum levels of all In investigation by parameters mentioned above Tariq et al., (2008) for the compared to positive control effects of different doses of group. ethanol on body organs of Cinnamon and ginger Japanese quails, results at the mixture group was the most end of 4th week revealed a pronounced amelioration significant effect on relative founded for kidneys’ functions weight of heart, kidney and indicators; uric acid and urea lungs in most treated groups. levels in hyperuricemic rats The increase in heart and lung groups. While the best weight was significant in quail treatment for the raised given 4% and higher ethanol, creatinine level was found in of kidney given 2 to 8% that group which treated with ethanol, while statistically no cinnamon 2%. effect was observed on relative weight of liver. Cinnamon contain cinnamaldehyde that may be a Data listed in table (3) potential compound for focused on serum uric acid, developing the pharmaceutics urea and creatinine of of anti-hyperuricemia agent as

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess mentioned by Wang et al., albino rats with renal (2008), who studied the effect dysfunction significantly of essential oil from leaves of decreased both serum urea and osmophloeum creatinine levels of rats acts as a xanthine oxidase compared with positive inhibitor and reduces the control rats. serum uric acid levels in oxonate-induced mice. Ginger significantly Moreover, Tanomand and reduces serum uric acid, urea Najafian, (2013) assessed the and creatinine, the inhibitory effects of cinnamon mechanisms of these extract on gentamicin-induced renoprotective effects may be nephrotoxicity in male adult outcomes of both oxidative wistar rats. The results showed stress and 6-gingerol, which that using cinnamon is demonstrated significant effective in decreasing blood antioxidant effects as recorded urea nitrogen, serum by Mahmoud et al., at (2012), creatinine and uric acid in who evaluated the effects of gentamicin – induced Zingiber officinale Roscoe nephrotoxicity, so that further (Ginger), Arabic gum (AG) improvements can be seen at and Boswellia on both acute higher doses. Due to the low and chronic renal failure cost of Cinnamon, ease of use (CRF) and the mechanisms and minimal side effects seem underlying their effects. to be less gentamicin as an Ginger and AG showed adjuvant treatment in order to renoprotective effects in both minimize damage to the models of renal failure. Ginger kidney. was more potent than AG in both models of renal failure. For the other herb, They mentioned also that oral Iroaganachi et. al, (2015) administration of ginger along recorded that ginger with adenine caused a supplementation for male significant improvement in

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess renal function, represented by have uricosuric effect and the significant decrease in hypouricemia. serum creatinine, urea, and BUN. Finally, they Data in Table (4) documented that ginger and demonstrated the activity of AG could be beneficial liver enzymes for adjuvant therapy in patients hyperuricemic rats as affected with acute renal failure and by herbs feeding. It could be CRF to prevent disease noticed that ethanol treatment progression and delay the need significantly (p<0.05) for renal replacement therapy. increased ALT, AST and ALP enzymes in the serum of These results are positive control group as agreed with those findings of compared to negative control Chyntiadewi, (2011), who one. While treated groups investigate the effect of significantly (p<0.05) ginger’s rhizome in decreasing decreased the raised serum uric acid level in levels of ALT and AST hyperuricemic rats, which activities when compared to induced by giving goat’s brain positive control group. Treated during eight days. Three groups with the two herbs at different dosages; 5, 10 and 2% additions and their mixture 20% of ginger’s rhizome were recorded also significant added for diets of (p<0.05) decrements in serum hyperuricemic rats. After level of ALP enzyme as fourteen days results showed compared to the positive that ginger’s rhizome can control one. decrease uric acid level in these rats. He elucidated that Treated group with the decrement of uric acid level mixture of herbs showed the for the active compounds in highest decrements in AST ginger’s rhizome; glycine, and ALP enzymes activity ascorbic acid, and fiber that levels of serum compared to positive control group. While,

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

Ginger1 % showed the highest malondialdhyde (MDA) level decrement in ALT enzyme and elevating antioxidants level of the serum compared enzymes activities; superoxide to positive control group. dismutase (SOD) and catalase (CAT). These findings agreed with Askari et. al, (2014), On the other hand, who documented that Sabina et. al, (2011) deduced supplementation with 1500 that 6-gingerol, an active mg powdered cinnamon daily/ ingredient of ginger, treatment 12 weeks decreased to acetaminophen-induced significantly ALT & AST in hepatotoxicity in mice showed patients with nonalcoholic significant hepatoprotective fatty liver disease. The effect by lowering the hepatic possible mechanism of this marker enzymes (AST, ALT, activity for cinnamon may be and ALP) and total bilirubin in due to free radical-scavenging serum (P<0.05). In addition, it polyphenols compounds. prevented the elevation of hepatic malondialdehyde The hepatoprotective formation and the depletion of properties were documented antioxidant status in the liver. by Moselhy and Ali at Ginger also has been reported (2009), who studied the to exhibit antioxidant potential hepatoprotective activity of and hepatoprotective activity aqueous and ethanolic extracts as recorded by Liu et al., of cinnamon against carbon (2013), who assessed the tetrachloride (CC14) induced effects of ginger essential oil lipid peroxidation and hepatic against alcoholic fatty liver injury in rats. The results disease in mice. Treatment obtained indicated that with ginger essential oil ethanolic extract has more administered every day for 4 potent hepatoprotective action weeks exhibited than water extract against hepatoprotective activity. CC14 by lowering the

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

Also in a study by significances were only in Shalaby and Saifan, (2014), groups fed on ginger 1% and revealed that cinnamon and cinnamon 2% and their ginger significantly reduced mixture for the levels of body weight gain and body fat albumin. No significance mass, normalized serum levels changes were recorded for of liver enzymes, also serum levels of globulin in all increased activity of kidney treated groups compared with antioxidant enzymes, positive control group. improved lipid fractions, These results were in decreased blood glucose and agreement with Kanani et. al, leptin, and increased insulin (2014), who documented that serum levels in obese diabetic globulin increased rats. significantly with ginger supplementation ( 1%) after Data listed in Table (5) 60 days of feeding for fisht. showed the serum proteins of Also, Oso et. al, (2013) hyperuricemic rats as affected confirmed that feeding dried by feeding on the studied ginger meal for keets 28-day- herbs. It is clear that the serum old male for 56 days increased levels of total protein (T.P) total serum protein and srum and albumin (Alb.) of positive albumin significantly (P control group significantly <0.05). decreased than negative control group, while globulin Results were in (Glb.) were insignificantly harmony with a similar study differed. Treatments for by ALGhwij et al., (2012), experimental groups with the who investigated the studied herbs and their protection effect of Curcumin mixture ameliorated these (CCM), Cinnamon (CNN) and decrements significantly Ginger (GE) against (p<0.05) in the levels of serum trichloroethylene (TCE)- total proteins, while induced hepatotoxicity and to

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess demonstrate its possible mode protein cast in the lumen of of action. The results showed renal tubules in rats’ kidneys that serum total protein did not compared with normal rats in changed in animals fed on photo 1. These findings were CCM and CNN alone than in agreement with Ligha et that of normal ones. On al., (2009), who documented adding of Herbal plants to that oral administration of TCE treatment, serum total alcohol caused structural protein was partially alterations in renal tubules, ameliorated with CCM and glomerular infiltration by CNN. On the other hand, no chronic inflammatory cells. significant changes were observed in rats treated with While, rats fed 1% TCE/GE. On adding of herbal ginger showed hypertrophy plants to TCE treatment, and congestion of glomerular serum albumin was partially tuft (photo 4), but with 1% ameliorated with CCM and cinnamon vacuolations at GE. On the other hand, no renal tubular epithelium were significant changes were noticed (photo 5). On the other observed in rats treated with hand, higher supplementations TCE/CNN because the with 2% of ginger or measurement of serum ALAT cinnamon or their mixture and albumin are more from groups didn’t show any the intestine. histopathological changes in kidneys of rats (photos 6, 7 & Histopathological 8), and that amelioration could investigations: be for the anti-inflammatory It could be noticed in characteristic of ginger and photos 2 & 3 that ethanol cinnamon. In consistent, treatment showed vacuolation Mahmoud et.al, (2014) at renal tubular epithelium and reported in-vivo study the perivascular inflammatory effects of dichloromethane cells infiltration, also showed extracts of ginger and

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess cinnamon in doses of 10 and ALGhwij, L.M.; Ghoneim, 20 mg/kg/day separately on 30 A. M.; Said, A. E. and Abd- experimentally infected albino Allah, G.A. (2012): rats with Giardia lamblia, one "Effect of Some Herbal of the most common Plants on Liver Function protozoal, evident revealed of Rats Treated with improvement for intestinal Trichloroethylene", The mucosal damage produced by Egyptian Journal of infection, and showed Hospital Medicine; Vol. restoration of normal villous 46, Page 7– 16. architecture and decrease in inflammatory cells in the Armitage, P. and Berry, G. lamina propria, these results (1987): were more obvious after “Statistical Methods in exposure to cinnamon Medical Researc", extracts. Blackwell, Oxford, UK, 93-213.

CONCLUSION Results could indicate Askari F.; Rashidkhani B. that using powdered ginger and Hekmatdoost A. (2014): and cinnamon may improve Cinnamon may have retarded kidney functions, therapeutic benefits on modulate liver enzymes lipid profile, liver activities and improve protein enzymes, insulin fractions. The mixture of resistance, and high- ginger and cinnamon recorded sensitivity C-reactive the most beneficial effects and protein in nonalcoholic could be used as hypouricemic fatty liver disease agent for gout disease. patients, Nutr Res., Vol. 34(2), Pp 143-8. REFERENCES

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", Food Chemistry; inhibitors: renaissance 94:520–528. half a century after the discovery of Moselhy, S. and Ali, H. . Pharmacol. (58); 1: 87– (2009): 114. "Hepatoprotective effect of Cinnamon extracts Proctor, P. (1970): against carbon Similar functions of uric tetrachloride induced acid and ascorbate in oxidative stress and liver man. Nature (5274); injury in rats." Biol. Res 228: 868. .42: 93-98. Reitman, S. and Frankel, S. Oso, A.O.; Awe, A.W.; (1957): Awosoga, F.G.; Bello, F.A.; A colorimetric method Akinfenwa, T.A. and for the determination of Ogunremi, E.B. ( 2013) : serum glutamic Effect of ginger oxaloacetic and glutamic (Zingiber officinale pyruvic transaminases. Roscoe) on growth Am. J. Clin. Path. , 28: performance, nutrient 56. digestibility, serum metabolites, gut Roy, S.E. (1970): morphology, and “Colorimetric determination microflora of growing of serum alkaline guinea fowl, Trop Anim phosphatase”, Clin. Chem., Health Prod., Vol. 45(8), 16:431-32. Pp1763-9. Sabina, E.P.; Pragasam, Pacher, P.; Nivorozhkin, A. S.J.; Kumar, S. and Rasool and Szabó, C. (2006): M. (2011): Therapeutic effects of 6-gingerol, an active xanthine oxidase ingredient of ginger,

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protects acetaminophen- Grad wholes clinical induced hepatotoxicity Laboratory Methods and in mice, Zhong Xi Yi Jie Diagnosis.Vol.18th Ed He Xue Bao., Vol. Mosby, London 258- 9(11):Pp 1264-9. 259.

Saravanan, G.; Tanomand, S. and Ponmurugan, P.; Deepa, Najafian,M.(2013): A.M. and Senthilkumar, B. "Inhibitory Effects of (2014): Cinnamon Extract on " Anti-obesity action of Gentamicin-Induced gingerol; effect on lipid Nephrotoxicity in Mail fractions, insulin, leptin, Adult Wistar Rats." amylase and lipase in Advances in male obese rats induced Environmental Biology, by a high-fat diet", 7(9): 2100-2104. Journal of the Science of Food and Agriculture, Tariq j., khuram s., Irfan, Article first published siddique1 and Cagiola online: 7 APR 2014. (2008): Effects of ethanol on Shalaby, M.A. and Saifan, different organs and on H.Y. (2014): fcr in quails, Pakistan Some pharmacological vet. j., 28(3): 119-124. effects of cinnamon and ginger herbs in obese Tausche, A.K., Unger, diabetic rats, J Intercult S. and Richter, K. Ethnopharmacolv.3 (4); (2006): Hyperurikämie 144-149. und Gicht [Hyperuricemia and Sonnenwirth, A. and Jaret, gout: diagnosis and L. (1980): therapy]. Der Internist. (5); 47: 509–20.

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Vitart, V.; Rudan, I. and Tetsuya, Y.; Moriwaki, Y. Hayward, C. (2008): and Takahashi, S. (2005): SLC2A9 is a newly "Effect of ethanol on identified urate metabolism of purine transporter influencing bases hypoxanthine, serum urate Xanthinem and uric concentration, urate acid". Clinical chemical excretion and gout, acta.(356);1-2:35-57. Nature Genetics, (4); 40: 437– 42. Vaibhavi, J.; Rakesh, P.; Pankaj, K. and Neeraj, P.; Wang, S.; Yang, C.; Liao, J.; Sunil, G.; Anupriya, P. and Zhen, W.; Chu, F. and Sonu, S. (2010): Chang, S. (2008): "Cinnamon: a "Essential oil from Pharmacological leaves of Cinnamomum Review", J.Adv.Sci.Res, osmophloeum acts as a 1(2); 19-23. xanthine oxidase inhibitor and reduces the Vangalapati, M.; Satya, S.; serum uric acid levels in Prakash, S. and Avanigadda, oxonate-induced mice. S. (2012): "Phytomedicine., A Review on 15(11):940-5. Pharmacological Activities and Clinical Yuri Y. Sautin, Witcha effects of Cinnamon Imaram, Kyung Mee Kim, Species", Research Alexander Angerhofer, Journal of George Henderson and Pharmaceutical, Richard Johnson.(2011): Biological and Chemical Uric Acid and Oxidative Sciences.3 (1): 653-661. Stress, Springer Science, Part 2, 143-159.

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Table (1): Effect of cinnamon and ginger on body weight gain (BWG %) and feed efficiency ratio (FER) of hyperuricemic rats

Parameters BWG (%) FER Groups

Control (– ve) 9.1 ± 2.15a 0.932 ± 0.04 a

Control (+ ve) 5.4 ± 1.89 bc 0.337 ± 0.02 bc

Ginger (1%) 2.5 ±0.39 cd 0.129 ± 0.02 c Cinnamon (1%) - 6.4 ± 1.55 e - 0.774 ±0.03 de

Ginger (2%) 3.8 ± 0.92 c 0.198 ±0.04 c

Cinnamon (2%) - 7.5 ±1.38 e - 0.9 ± 0.04 de

Mixture of Ginger and Cinnamon - 2.3 ±0.84 d - 0.323 ± 0.03 d (1+1%) - Values are expressed as mean ± SD. - Significance is expressed at p<0.05 using one way ANOVA test. - Values with different letters in each column have differed significantly, while the difference among those with similar letters completely or partially is not significant.

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Table (2): Effect of cinnamon and ginger on relative organs’ weight of hyperuricemic rats Relative Weight parameters Liver Heart Kidneys Groups 3.098 de 0.343 d 0.620 cd Control (– ve) ± 0.170 ± 0.030 ± 0.052 4.600 a 0.570 a 1.55 a Control (+ ve) ± 0.447 ± 0.057 ±0.11 Ginger (1%) 3.966 b 0.450 bc 1.167 ab ± 0.151 ± 0.055 ± 0.082 b ١.٠٠٠ Cinnamon (1%) 3.517 c 0.495 b ٠.٠٨٩ ± 0.039 ± 0.194 ± Ginger (2%) 3.717 bc 0.375 d 0.955 b ± 0.147 ± 0.040 ± 0.087 Cinnamon (2%) 3.432 cd 0.485 b 0.916 bc ± 0.139 ± 0.019 ± 0.683 Mixture of Ginger 3.367 d 0.351 d 0.800 c and Cinnamon ± 0.163 ± 0.029 ± 0.071 (1+1%) - Values are expressed as mean ± SD. - Significance is expressed at p<0.05 using one way ANOVA test. - Values with different letters in each column have differed significantly, while the difference among those with similar letters completely or partially is not significant.

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

Table (3): Effect of cinnamon and ginger on uric acid, blood urea nitrogen, urea and creatinine of hyperuricemic rats Parameters Uric Urea Creatinine

Acid(mg/dl) (mg/dl) (mg/dl) Groups 1.61 b 30.8 cd 0.52 c Control (– ve) ±0.19 ±2.14 ±0.07 2.2 a 38.33 a 1.21 a Control (+ ve) ±0.08 ± 4.47 ±0.08 Ginger (1%) 1.4 b 35.4b 0.65 bc ±0.07 ± 1.8 ±0.05 Cinnamon (1%) 1.58 b 31.6 cd 0.78 b ±0.21 ±3.88 ±0.16 Ginger (2%) 1.4 b 34.6bc 0.78 b ±0.32 ±3.01 ±0.12 Cinnamon (2%) 1.48 b 33.8 bcd 0.62 bc ±0.26 ±3.45 ±0.12 Mixture of Ginger 1.28 c 28.4 d 0.66 bc and Cinnamon ±0.28 ±1.82 ±0.17 (1+1%) - Values are expressed as mean ± SD. - Significance is expressed at p<0.05 using one way ANOVA test. - Values with different letters in each column have differed significantly, while the difference among those with similar letters completely or partially is not significant.

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

Table (4): Effect of cinnamon and ginger on the activity of liver enzymes of hyperuricemic rats Parameters ALT U/L AST U/L ALP U/L Groups 22.1 cd 22.1 bc 463.7 bc Control (– ve) ±6.67 ±3.713 ±66.18 35.57 a 27.57 a 625.77 a Control (+ ve) ±3.06 ±4.399 ±106.9 Ginger (1%) 19 d 23.65 bc 549.1 ab ±2.23 ±4.562 ±118.3 Cinnamon 29.5 b 23.3 bc 494.5 abc (1%) ±4.93 ±4.774 ±105.7 Ginger (2%) 26.7 cd 25.7 b 460.1 bc ±5.66 ±6.269 ±133.3 Cinnamon 25.7 cd 21.1 bc 425.1 bc (2%) ±4.66 ±3.561 ±134.5 Mixture of Ginger and 22 cd 19.3 c 364.9 c Cinnamon ±3.5 ±2.14 ±101.2 (1+1%) - Values are expressed as mean ± SD. - Significance is expressed at p<0.05 using one way ANOVA test. - Values with different letters in each column differed significantly, while the difference among those with similar letters completely or partially is not significant.

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Table (5): Effect of cinnamon and ginger on serum proteins (T.P, Alb and Glb ) of hyperuricemic rats Parameters T.P mg/ dl Alb mg/ dl Glb mg/ dl Groups

Control (– ve) 6.2 ±0.38 a 3.94 ±0.31 a 2.26 ±0.39 b

Control (+ ve) 5.033 ±0.05 b 2.2 ±0.14 d 2.833 ±0.19 ab Ginger (1%) 6.45 ±0.50 a 3.6 ±0.26 abc 2.85 ±0.73 ab Cinnamon 6.12 ±0.96 a 3.4 ±0.11 cd 2.72 ±0.96 ab (1%) Ginger (2%) 6.78 ±0.51 a 3.48 ±0.07 bcd 3. 3 ±0.57 a Cinnamon 6.34 ±0.37 a 3.8 ±0.46 ab 2.54 ±0. 7 ab (2%) Mixture of Ginger and 6.64 ±0.76 a 4 ±0.31 a 2.64 ±0.63 ab Cinnamon (1+1%) - Values are expressed as mean ± SD. - Significance is expressed at p<0.05 using one way ANOVA test. - Values with different letters in each column differed significantly, while the difference among those with similar letters completely or partially is not significant.

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• Kidney

Photo (1): Kidney of rat from negative Photo (2): Kidney of rat from positive control group showing the normal control group showing vacuolation of histological structure of renal renal tubular epithelium and parenchyma (H & E X 400). perivascular inflammatory cells infiltration (H & E X 400).

Photo (3): Kidney of rat from positive Photo (4): Kidney of rat fed on ginger control group showing protein cast in the 1% showing hypertrophy and lumen of renal tubules (H & E X 400). congestion of glomerular tuft (H & E X 400).

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess

Con.

Photo (5): Kidney of rat fed on cinnamon 1% showing vacuolations of renal Photo (6): Kidney of rat fed on ginger tubular epithelium (H & E X 400). 2% showing no histopathological changes (H & E X 400).

Photo (8): Kidney of rat fed on mixture Photo (7): Kidney of rat fed on cinnamon of ginger and cinnamon showing no 2% showing no histopathological changes histopathological changes (H & E X 400). (H & E X 400).

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Effects of Feeding Some Herbs on Hyperuricemic Rats Walaa I.M. Aniess تأثير التغذية ببعض األعشاب على الجرذان المصابة بارتفاع يوريا الدم

والء إبراھيم محمد أنيس قسم االقتصاد المنزلي، كلية التربية النوعية، جامعة عين شمس.

المستخلص العربي:

النقرس ھو شكل اللتھاب في المفاصل مصحوب بارتفاع حامض البوليك وترسب بلورات اليوريا أحادية الصوديوم بھا. ھدفت ھذه الدراسة إلى استكشاف التأثيرات المفيدة من إطعام طحين الزنجبيل و/ أو القرفة للجرذان المصابة بارتفاع اليوريا على األعراض المصاحبة لمرض التقرس بالدم. تم تقسيم ٤٩ ذكر بمتوسط وزن ١٩٢ ±٢٣ جم إلى سبعة مجموعات متساوية كاآلتي: مجموعه ضابطه سالبة تغذت على الغذاء األساسي فقط، بينما الستة مجموعات األخرى تم حقنھم بالفم باإليثانول ( ١.٨ جم / كجم من وزن الجسم) كل ٢٤ ساعة لمدة ثمانية أيام متتالية إلحداث ارتفاع في مستوى اليوريا بالدم، وبعد التأكد من حدوث اإلصابة تم تغذيتھم على: غذاء أساسي فقط ( ضابطه موجبة)، أو مع إضافة نسبة ١% زنجبيل، ١% قرفه، ٢% زنجبيل، ٢% قرفه أو خليط منھما ١%+ ١% من إجمالي وزن الغذاء بعد فترة تھيئة مالئمة. تم قياس مستويات حامض البوليك، اليوريا والكرياتينين، نشاط أنزيمات الكبد ( ALT, AST and ALP ) ومستويات األلبيومين والجلوبيولين بمصل الدم. كشفت النتائج ان الدعم بالزنجبيل والقرفة أو خليطھما لغذاء الجرذان التى تعانى من إرتفاع مستوى اليوريا بالدم قد أدت إلى اآلتى: نقص نسب الكفاية الغذائية، الحد من تضخم الوزن النسبى للكبد والكليتين بشكل يتماشى والنسبة المضافة، نقص بشكل معنوى فى إرتفاع مستويات حامض البوليك واليوريا والكرياتينين، الحد من إرتفاع مستويات نشاط إنزيمات الكبد ALT, AST وALP ، كذلك الحد بشكل معنوى من التقص فى مستويات البروتين الكلى واأللبيومين بمصل الدم وذلك بالمقارنة بالمجموعه الضابطه الموجبة. كشف الفحص النسيجى للكلى أن الدعم بالمستويات األعلى من الزنجبيل والقرفه (٢%) أو خليطھما قد أصلح من التشوھات الناجمه عن المعالجه باإليثانول والتى ظھرت فى المجموعه الضابطه الموجبه. ھذه المردودات يمكن أن تشير إلى أن إستخدام الزنجبيل والقرفة قد تحسن من وظائف الكلى، إنزيمات الكبد وبروتينات الدم، وباألخص خليطھما والذى اظھر معظم التأثيرات اإليجابية المرصوده، حيث يمكن إستخدامه كعامل خافض لمستويات اليوريا بالدم فى مرض النقرس كعالج مساعد.

الكلمات المفتاحية: زنجبيل، قرفه، التغذية، إرتفاع يوريا الدم، الجرذان، أنزيمات الكبد، وظائف الكلى وصورة بروتين الدم.

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