{"id":3157,"date":"2015-12-28T10:54:33","date_gmt":"2015-12-28T10:54:33","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=3157"},"modified":"2016-05-10T07:40:36","modified_gmt":"2016-05-10T07:40:36","slug":"protective-effect-of-zizphus-vulgaris-extract-on-liver-toxicity-in-laboratory-rats-2","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol8no2\/protective-effect-of-zizphus-vulgaris-extract-on-liver-toxicity-in-laboratory-rats-2\/","title":{"rendered":"Protective Effect of Zizphus Vulgaris Extract, on Liver Toxicity in Laboratory Rats"},"content":{"rendered":"<p><strong>Introduction<\/strong><\/p>\n<p>Liver plays a significant role through \u00a0many necessary physiological processes such as homeostasis\u00a0 glucose,\u00a0 necessary\u00a0 proteins preparation for plasma ,lipoprotein ,lipid preparation and secretion of bill acids ,and saving vitamins(1) .there is no certain reason for liver disease, but oxidation\u00a0 factors definitely are instrumented in providing liver pathology changes ,especially through poisoned and alcoholic livers. It occurs when those compounds bring about disorder in biological\u00a0 \u00a0membranes of cell membranes structure and finally cause pathological changes. Mostly different restraint mechanisms of the body are not able to operate as mere protective role and need some assisting compounds especially nutritional anti-oxidants .usually some natural compounds have the anti-oxidant qualities in which they have great importance in liver protection against destructive factors (2,3).<\/p>\n<p>Zizphus jujube is a suitable example, including natural and herbal\u00a0 compounds which has a long story for medication usage. Jujube\u00a0\u00a0\u00a0 was applied in Eastern Asian countries for healing diseases like liver disorders, Anemia and asthma (4,5). observations have demonstrated that Jujube plant has active compounds and these compounds include protective effect on Histamine \u00a0\u00a0release ,activation of Cyclooxygenases <em>1and<\/em> <em>11<\/em>,Cholinestrase (6).Jujube includes mucilage, \u00a0malic\u00a0 acid ,citric acid ,vitamin C(7) and along with sugar elements up 2.17-6.5 per cent, protein elements , organic materials, compounds tripnoid, \u00a0Flanoid and\u00a0 jojuphnoenosid (8).<\/p>\n<p>Gong Cheng et al (2000)have attributed some medical feature of ZiZphus\u00a0 Jujube plant to its anti-oxidant qualities by extracting eight flanoeid types out of jujube(9).<\/p>\n<p>Welli et at (2007),through an observation ,along with description of some vast medicinal features of Jujube in traditional\u00a0 and modern Chinese\u00a0 medicine ,have\u00a0 added that due to the presence\u00a0 of a type of proteoglycan\u00a0 in the fruit \u00a0up this plant, Jujube stands out as a good source of medicinal qualities\u2019(10).\u00a0 Based on the presence of\u00a0 various chemical compounds and\u00a0 anti-oxidants features of Jujube , this observation conducted on rats(rice wistar) regarding the effect of\u00a0 Jujube fruit essence on liver protection.<\/p>\n<p><strong>\u00a0Materials and Methods<\/strong><\/p>\n<p>An experimental observation was conducted in Yasuj medical sciences university in 201o. thirty mature rats heads ,male healthy ,were chosen from wistar\u00a0 species and were accidentally divided into five equal groups as follow:<\/p>\n<p>Control groups that received olive oil twice a week- Sunday and Wednesday \u2013for amount of one cc( cubic centimeter\u00a0 ) of body\u00a0 weight\u00a0 for each kilo grams through peritoneum injection. Simultaneously this group accepted 0.5cc distilled water through gavage. Another group was witness group that also got 50-50 olive oil solution and carbon tetrachloride in amount of one milliliter for each kilo gram of body weight through peritoneum injection.<\/p>\n<p>witness group received o.5 cc distilled water through gavage as well.<\/p>\n<p>Finally, three intervention groups of 1, 2 and 3 that simultaneously received<\/p>\n<p>50-50- olive oil and carbon tetrachloride in amount of one milliliter for each kilo gram of body weight. in addition , hydro alcoholic essence made from plants was gavaged in different doses of 200, 400, 600 milligram respectively to groups of 1 ,2 ,and 3.<\/p>\n<p>To get essence from jujube fruit, it first was dried and ground to powder. Then 500 grams of powder was\u00a0\u00a0 added to water, ethanol blended with \u00a0\u00a0the ratio of 1 to 1 to be soaked and strained for 24 hours .this action was operated into two processes .Jujube fruit was dried under vacuum condition and 50 centigrade of heat.The essence was again dried in incubator and was distilled with distilled water to the final volume of 500 milliliter .this product was kept in 10 milliliter vials in freezer \u00a0-20 centigrade \u2013till the time of usage .the rats were weekly weighted .the doses of essence and carbon tetrachloride kept changing based on new weight. After 45 days. The rats were anaesthetized by diethyl ether and blood sampling was directly done from their hearts. The result was spinal cord paralysis from. Innards were macroscopic observed .each rats liver was weighted and sent to laboratory for pathology. A serum was produced out of the blood of each rat. These serums applied for measuring Aspartat amino transfer, Alanine amino transfers\u00a0 \u00a0enzyme , alkaline \u00a0phosphates enzyme ,total protein ,albumin and bilirubin.<\/p>\n<p>liver samples were fixed\u00a0\u00a0 after weighting in natural formalin .<\/p>\n<p>buffered solution -10 per cent .sample were put in paraffin, and cut in wide wage\u00a0 , painted by hematoxilin \u00a0eosin. Inflammation degree of portal and necrosis in liver cells \u2013in half form \u2013were observed by two pathologists.<\/p>\n<p>the consequence in fact was divided into four categorises of no histologist change\u00a0 (degree Zero) ,slight histologist changes (degree one),average histologist changes(degree two),intense histologist (degree three),through SPSS soft ware along with statistical tests analyses variance(one way) and T-test.<\/p>\n<p><strong>Results:<\/strong><\/p>\n<p>Finding consequences indicated that the average and deviation standard for protein and albumin density in rats stand respectively out 7\/11+_o\/37 and 3\/82+_o\/13 milligram per cent for control group,3\/76+_0\/\/49 and 3\/76+_0\/021, or witness group ,7.06+_0\/09and7.06+_0\/09\u00a0 for first intervention(experimental) \u00a0group ,6\/9+_0\/25 and 3\/75+_0\/91 for second intervention(experimental) \u00a0group, \u00a06\/65+_0\/91and 3\/7+_0\/28 for third invention g(experimental) group. According to consequence, significant \u00a0difference was seen between control groups , \u00a0witness and intervention.<\/p>\n<p>The average density of total and direct bilirubin also were respectively determination as 0\/16+_0\/13 and 0\/28+_0\/07 for control group, 0\/22+_0\/17and 0\/48+_0\/21for witness group, 0\/07+_0\/09and 0\/27+_0\/05 for first intervention (experimental) group, 0\/10+_0\/11 and 0\/30+_0\/08 for second group intervention(experimental), and 0\/25+_0\/12 and 0\/52+_0\/17 for third intervention group .this shows that witness group in comparison with control group has significant difference\u00a0 in total bilirubin (p&lt;0\/05).<\/p>\n<p>There is significant\u00a0 deference between first intervention(experimental) group and witness group in total and direct bilirubin (p&lt;0\/05) as well ,but there seems no important difference between second and third intervention(experimental) \u00a0groups in\u00a0 comparison with witness group(p&lt;0\/05).in table 1, the average\u00a0 of standard deviation for liver enzymes, density\u00a0 group is shown, so that there is not found significant difference in density of alkaline phosphates\u00a0 and Asparate transfer and Alanine transfer enzyme in groups of control ,witness ,and intervention (experimental) (p&lt;0\/05).<\/p>\n<p>The research findings show that the average for liver weight to body weight in control group,3\/93+_0\/25, witness group 4\/25+-0\/36 ,intervention ((experimental) group one 4\/67+0\/94, intervention ((experimental) group two 4\/10+-0\/29 and intervention ((experimental) group three was 4\/71+-10 mg.<\/p>\n<p>That no significant difference was observed among the control group, witness group, and intervention (experimental) groups (p&lt;0\/05).<\/p>\n<p>histopathological observation results demonstrated that width wise cut of liver in normal animals \u00a0shows ,normal cells along with healthy cytoplasm and central nucleus and vein. In animals, those with usage of tetrachloride carbon, liver cells show high rate of rain in necrosis and portal.<\/p>\n<p>In poisonous cells by tetrachloride carbon and cured by Jujube very slight alteration was found along with almost normal structure in third intervention (experimental) group. Treatment by Jujube -600milligram as body weight in kilo gram \u2013was remarkable in\u00a0 liver necrosis due to tetra chloride\u00a0 carbon .It also causes reduction in inflammation of portal cells .but in second intervention(experimental) \u00a0group it was seen more rain in cells and\u00a0 reduction in inflammation of portal cells .to same extent , alteration in liver cells was normal.\u00a0 in the first intervention (experimental) group necrosis cells and liver portal\u00a0 inflammation was of higher and less rats of treatment in comparison with other two groups .It remarkable difference was also seen between this group and other groups regarding\u00a0 liver\u00a0 cells necrosis (p&lt;0\/05),but there was no difference in inflammation of portal cells .the main difference was the \u00a0general rate of liver structure ruin with second and third intervention(experimental) \u00a0groups (p&lt;0\/05).treatment -200 and 400 milligram as body weight in kilogram \u2013causes reduction in liver necrosis and inflammation of portal area.<\/p>\n<p><strong>Table 1: the average of standard deviation for liver enzymes<\/strong><\/p>\n<table style=\"width: 90%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" width=\"174\"><strong>group<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"168\"><strong>Alkaline phosphatas enzyme<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"150\"><strong>Asparat transfras enzyme<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"144\"><strong>Alanine transfras enzyme<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"174\">Control<\/td>\n<td style=\"text-align: center;\" width=\"168\">837+_155<\/td>\n<td style=\"text-align: center;\" width=\"150\">139+_16<\/td>\n<td style=\"text-align: center;\" width=\"144\">160+_20<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"174\">witness<\/td>\n<td style=\"text-align: center;\" width=\"168\">852+_145<\/td>\n<td style=\"text-align: center;\" width=\"150\">143+_29<\/td>\n<td style=\"text-align: center;\" width=\"144\">163+_10<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"174\">\u00a0First intervention<\/td>\n<td style=\"text-align: center;\" width=\"168\">875+_137<\/td>\n<td style=\"text-align: center;\" width=\"150\">137+_50<\/td>\n<td style=\"text-align: center;\" width=\"144\">194+_53<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"174\">\u00a0Second intervention<\/td>\n<td style=\"text-align: center;\" width=\"168\">792+_103<\/td>\n<td style=\"text-align: center;\" width=\"150\">138+_30<\/td>\n<td style=\"text-align: center;\" width=\"144\">160+_12<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"174\">\u00a0Third intervention<\/td>\n<td style=\"text-align: center;\" width=\"168\">486+_156<\/td>\n<td style=\"text-align: center;\" width=\"150\">160+_63<\/td>\n<td style=\"text-align: center;\" width=\"144\">183+_26<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"174\">Significant<\/td>\n<td style=\"text-align: center;\" width=\"168\">&lt;0\/05<\/td>\n<td style=\"text-align: center;\" width=\"150\">&lt;0\/05<\/td>\n<td style=\"text-align: center;\" width=\"144\">&lt;0\/05<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p><strong>Discussion and Conclusion<\/strong><\/p>\n<p>Liver is the main organ of metabolism ,splash\u00a0 and excretion of materials and is continuously exposed to different types of external and \u00a0\u00a0internal compounds .the outbreak of liver diseases is\u00a0 universally expanding and not only man-made chemical medication are not completely useful and function in curing of diseases but also undesirable and risky have vital effects ;therefore there is a need to a suitable substitution entering to medical science for curing liver diseases(2) .the aim of this experiment was the effect of Jujube essence for liver protection on rats.<\/p>\n<p>The results demonstrated that alteration of enzyme rate in witness group had a slight increase in comparison control group. In intervention(experimental) \u00a0group-received 200 milligram of Jujube essence \u2013liver enzyme rate had shown an increase comparing\u00a0 with witness group but in intervention(experimental) \u00a0group received 400 and 600 milligram of Jujube essence the rate of liver enzymes were decreased in comparison with witness group. This reduction was even more in intervention (experimental) group received 400 milligram of essence. Disorder in unity of plasma membrane -liver cells-causes enzymes entrance-which are naturally in cytosol -into blood circulation, that is the indictor and standard for observing liver condition. One of the major standards of liver damages due to toxin is increasing of liver enzymes activity in serum.<\/p>\n<p>reactivity\u00a0 of liver enzymes to natural\u00a0\u00a0 state and also reduction of bilirubin density and increasing\u00a0 of total protein and albumin serum are of main standards in liver cure and recovery of this prominent organ(1).<\/p>\n<p>Another important consequence indicates that total and direct bilirubin density in witness group, received just tetra chloride carbon increased comparing with control group.<\/p>\n<p>It happens due to liver cells ruin and lack of protection substance .In addition, application of Jujube essence within first and second intervention (experimental) \u00a0groups provided less bilirubin density. This density also within third intervention (experimental) group increased comparing with witness group. It can indicat the opposit influence of Jujube in more dose on bilirubin degree (5,6,7).<\/p>\n<p>In study conducted by Nabavi Zadeh et al (2004) the influence of drug plants hydro alcoholic extract was observed on hyperbilirubinemia kid. the result showed not sufficient decrease in bilirubin density by the plant(11).<\/p>\n<p>In this study no difference between the average of albumin and total protein density within observed groups was demonstrated, since protein and albumin serum are impressed through persistent liver disease (11).<\/p>\n<p>the study of Abrahimi at el (2010) showed that\u00a0 The results indicate that <em>Zizyphus jujuba <\/em>was effective for the treatment of neonatal jaundice in the \u00a0first 12 hours of treatment compared to controls which could be due to higher effect of Z. jujuba extract to reduce bilirubin concentration with different mechanisms.(12)<\/p>\n<p>and rats kidney damages were sharp and remarkable ;hence these consequences appear greatly acceptable.<\/p>\n<p>Rats weights increased within witness and intervention (experimental) groups. These alterations were more within the first and second groups.<\/p>\n<p>The average percent of liver comparing with rats, body weight was observed through investigating groups. Since injection of tatra chroride carbon causes damage to liver and provides disorder metabolism in rats bodies, it also causes less rat body weight and liver enlargement, that is one of the characteristics of hepatotoxic compounds. Liver damages and particularly fibrotic damages prepare enlargement and firmness (13).<\/p>\n<p>In this research, too, the ratio has increased in witness group in comparison with the control group. The revision percent of the livers weight attribution to the rats body weight has been demonstrated in the intervention ((experimental) group one and three to the witness group.<\/p>\n<p>Histopathology results showed there was not remarkable difference in \u00a0groups under observation. Consequence of observation done by Pervaded et al (2002) showed that alcoholic resin of pistachio essence has protection effects on liver against tetra chloride carbon that it might be related to flanoid per cent in resin (14). In another study, it has been indicated that alcoholic essence of plant is able to decrease necrosis, fat changes and hepatocyte\u00a0 swelling.This plant might be able to some effects of gathering free radicals or able to control these productions(9).<\/p>\n<p>The results of observations carried out by Ayato llahi et al (2007) indicated that alcoholic essence of Cilimarine plant in 50 milligram to kilogram dose helps to a great extent in prevention from liver necrosis expansion and increasing of enzyme activity \u00a0due to \u00a0tatra\u00a0 chroride carbon injection. It also helps and prepares the recovery for degenration process and textural damages (15).<\/p>\n<p>Generally, the results of this observation demons treated that Jujube is highly, able to have protection effects against carcinogenic and toxic factors on liver cells.<\/p>\n<p>It seems that more studies and research are \u00a0required to show these \u00a0compounds effects on mechanism of protection influencing on poisonous liver cells.<\/p>\n<p><strong>References<\/strong><\/p>\n<ol>\n<li>Androli T, Carpenter C, Griggs R, Benjamin I. Diseases of the Liver and Biliary System. in: Cecil&#8217;s Essentials of Medicine. 7<sup>th<\/sup> ed. USA: WB Saunders Company; 2007; 23.<\/li>\n<li>Luper S. A review of plants used in the treatment of liver disease. Alternatvie medicine Review 1998; 3: 40-2.<\/li>\n<li>Ulicna O, Greksak M, vancova O, Zlatos L, Galbaw S, Bozek P, et al. Hepato protective effect of rooibos tea (Aspalathus linearis) on ccl4- induced liver damage in Rat. Physiological Research 2003; 52: 461-6.<\/li>\n<li>Zargari A. Herbal remedies. 6<sup>th<\/sup> ed. Tehran: University Press; 1998; 587-607.<\/li>\n<li>Fluk Hans, Translated by Tavakoli M, Sedaght M. Herbal medicine. 4<sup>th<\/sup> ed. Tehran: Roozbahan Publications;1992;171-91.<\/li>\n<li>Khalili M. teb Alsadegh. Translated by Amir Sadeghi Tehrani. 5<sup>th<\/sup> ed. Tehran: Atayi Publications; 1970; 183.<\/li>\n<li>Smsam Shariat H. Herbal medicine that classified according to their usage in traditional and modern medicine. Isfahan: Chaharbagh; 2006;137.<\/li>\n<li>Cheng Q. Flavonoids from ziziphus jujube mill var. Spinosa tetrahedron 2000; 56: 8915-8920.<\/li>\n<li>Zhao J. Simultaneous determination of saponins and fatty acids in ziziphus jujuba (suanzaoren) by high performance liquid chromatography evaporative light scattering detection and pressurized liquid extraction. Journal of Chromato Graphy A 2006;1106: 188-94.<\/li>\n<li>Weili JN. Isolation and analysis of anovel proteoglycan from ziziphus jujuba . Journal of Food and Drug Analysis 2007;15(3): 271-7.<\/li>\n<li>Nabavizadeh SH, Safari M, Khoshnevisan F. Direct ex vivo effects of herbal extracts on serumbilirubin in neonatal blood samples. Iranian Journal Of Pediatrics\u00a02005;15(2):133-8.<\/li>\n<li>Sedigheh Ebrahimi1, MD; Soheil Ashkani-Esfahani, and Azizollah Poourmahmudi, Investigating the Efficacy of Zizyphus Jujuba on Neonatal Jaundice Iranian Journal of Pediatrics, Volume 21 (Number 3), September 2011, Pages: 320-324.<\/li>\n<li>Sabz Ali S. Hepatic protection effects of plant Chicorium intybus on liver toxicity induced by carbon tetrachloride in rats. Medical Doctoral Thesis 2005; 54-51:10-26.<\/li>\n<li>Parvardeh S, Nyapur M, Hosseinzadeh H. Hepatic protection effects of hydraulic extract of Pistachio gum on carbon tetrachloride-induced liver toxicity in ratsMedicinal Plants. No IV Fall 2002; 1: 34. 15. Jamshid Nejad A, Nick nahad H. Hepatic protection effects\u00a0 of plant Fumaria officinalison liver toxicity induced by carbon tetrachloride in rats. Journal of Medicinal Plants 2006; 19(5):34-9.<\/li>\n<li>Ayatollahi H, Abbasali o, Kasebi M. Hepatic protection effects\u00a0 of plant Silybum marianum on liver toxicity induced by carbon tetrachloride in mice. Journal of University of Medical Sciences of Gorgan 2007; 4: 56.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Introduction Liver plays a significant role through \u00a0many necessary physiological  [&#8230;]<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[],"class_list":["post-3157","post","type-post","status-publish","format-standard","hentry","category-vol8no2"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/3157","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=3157"}],"version-history":[{"count":4,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/3157\/revisions"}],"predecessor-version":[{"id":6318,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/3157\/revisions\/6318"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=3157"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=3157"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=3157"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}