|Year : 2012 | Volume
| Issue : 4 | Page : 208-213
Comparative study on the hepatoprotection to heavy metals of Zingiber officinale
Chukwuemeka R Nwokocha1, Daniel U Owu1, Magdalene I Nwokocha2, Chibueze S Ufearo3, Moses O. E. Iwuala4
1 Department of Basic Medical Sciences, University of the West Indies, Mona Campus, Nigeria
2 Department of Basic Medical Sciences, Kingston Public Hospital, Kingston, Jamaica, Nigeria
3 Department of Basic Medical Sciences, Nnamdi Azikiwe University, Nnewi, Anambra State, Nigeria
4 Department of Basic Medical Sciences, Federal University of Technology, Owerri, Imo State, Nigeria
|Date of Submission||18-Oct-2011|
|Date of Decision||23-Nov-2011|
|Date of Web Publication||11-Oct-2012|
Chukwuemeka R Nwokocha
Department of Basic Medical Sciences, University of the West Indies, Mona Campus,Kingston 7, Jamaica
| Abstract|| |
Context: Zingiber officinale (Zingiberaceae) is a herb used for culinary and therapeutic purposes due to its anti-inflammatory and antioxidant potentials. Objectives: We examined its protective ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. Materials & Methods: Ground Zingiber officinale (7%, w/w of feed) was administered to rats either at the same time with the exposure ofheavy metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. Animals were exposed to either of Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) in drinking water. The heavy metal accumulations in the liver were determined using AAS. Results: Weight losses induced by these metals were not reversed by Zingiber officinale administration. There was a significant (P<0.01) increase in protection to Pb (97%) and Cd (63%) accumulation when compared to Hg (32%) at week 2. The protective ability was significantly (P<0.01) decreased at week 4 when compared to week 2 for Cd and Pb but not to Hg in groups 3 (50%) and 4 (52%). At week 6, hepatoprotection to Hg (44%) and Cd (85%) was significantly (P<0.01) different but not to Pb which was only significant (P<0.05) in week 2 of treatment for all groups. Discussion and Conclusion: Zingiber officinale affected the bioavailability, elimination and uptake of these metals in a time-dependent way with highest beneficial reducing effect to Cd followed by Hg and least protection to Pb in the liver.
Keywords: Accumulation, cadmium, lead, liver, mercury, protection, Zingiber officinale
|How to cite this article:|
Nwokocha CR, Owu DU, Nwokocha MI, Ufearo CS, Iwuala MO. Comparative study on the hepatoprotection to heavy metals of Zingiber officinale. Phcog Res 2012;4:208-13
|How to cite this URL:|
Nwokocha CR, Owu DU, Nwokocha MI, Ufearo CS, Iwuala MO. Comparative study on the hepatoprotection to heavy metals of Zingiber officinale. Phcog Res [serial online] 2012 [cited 2013 Dec 6];4:208-13. Available from: http://www.phcogres.com/text.asp?2012/4/4/208/102263
| Introduction|| |
Oxidative stress, altered physiological and biochemical characteristics , leading to organ damage ,,, occur with heavy metal exposures. Heavy metals impart their toxicological effects mainly through molecular interactions with sulfhydryl groups on various molecules, ,,,,,,,,, generation of reactive oxygen species (ROS) and weakening the antioxidant defense system of cells and altering calcium and Fe 2+ channels transport. ,
Zingiber officinale (ginger), an aromatic but pungent food spice, is used for its medicinal value. ,,,,,,,,, It's antioxidant properties  contribute to its radical scavenging properties, a characteristic suited for metal chelation and hepatoprotection. , Antioxidant supplementation is reported to be beneficial in metal toxicity.  This study is performed to comparatively analyze the hepatoprotection of Zingiber officinale to lead (Pb), cadmium (Cd) and mercury (Hg) accumulation in the liver of rats.
| Materials and Methods|| |
Animals and experimental design
Male Wistar rats of about seven-week-old weighing 150-180 g were obtained from the Animal house of the Faculty and used for the study. The animals were kept at constant room temperature with 12 h of light/dark cycles. The individual animal body weight was recorded weekly throughout the experiment. All animals were fed with normal rat chow and had access to tap water ad libitum during the period of acclimatization. We sought and received ethical approval from the Faculty Ethical Committee for this study.
Preparation of nutrient substance and heavy metals
Fresh ginger rhizome was purchased from the main market at Nnewi Nigeria. Ground and sieved (particulate size of 250 μm) Zingiber officinale were mixed with rat chow (7% w/w of Zingiber officinale in rat chow) and fed to the animals. Pb-exposed groups received tap water that contained 100 ppm lead acetate. Cadmium-exposed groups received tap water that contained 200 ppm cadmium chloride while mercury-exposed groups received tap water that contained 10 ppm mercury chloride water directly from the drinking water bottle.
Group 1 was fed with normal rat chow and either one of the heavy metals in drinking water (Cd = 200 ppm, Hg = 10 ppm, Pb = 100 ppm). Group 2 was fed with rat chow mixed with 7% Zingiber officinale and either one of the heavy metals in drinking water (Cd = 200 ppm, Hg = 10 ppm, Pb = 100 ppm). The exposure and feeding started at the same time. Group 3 was fed with normal rat chow and either of the heavy metal (Cd = 200 ppm, Hg = 10 ppm, Pb = 100 ppm) in drinking water for the first week and then with rat chow mixed with Zingiber officinale and tap water from the second to the sixth week. Group 4 was fed with rat chow mixed with Zingiber officinale for one week. After that they were fed with normal rat chow and either one of the heavy metal (Cd = 200 ppm, Hg = 10 ppm, Pb = 100 ppm) in drinking water for the remaining 5 weeks. The grouping and feeding patterns are summarized in [Table 1]. All administrations were through the oral route.
Tissue preparation and analysis
At the end of the experimental period, the rats were sacrificed under chloroform anesthesia. Liver (1g) was excised and transferred in polypropylene vials for analysis. Before acid digestion, a porcelain mortar was employed to grind and homogenize the dry tissue samples in 5 ml of normal saline. After digestion, in all samples, the concentrations of Pb and Cd were analyzed using flame atomic absorption spectrophotometer (Perkin Elmer A.A. 3030) with D2 background correction device. Cold vapor technique was used for the analysis of Hg. ,
The results are expressed as mean ± SEM. Student's t-test and two-way analysis of variance (ANOVA) with Bonferonni's post-test was performed, where applicable, using Graph Pad Prism version 5.0 for Windows (GraphPad Software, San Diego, Ca, USA). A P value of 0.05 was considered statistically significant.
| Results|| |
Body weight changes
It was observed that the treatment of the animals with both nutrients and heavy metals significantly (P< 0.05) reduced the body weight when compared with animals not exposed to any of the nutrients or heavy metals [Figure 1]. Zingiber officinale administration also significantly (P<0.05) reduced the body weight. Zingiber officinale did not significantly alter the weight loss induced by Hg and Cd exposures, but caused a significant (P<0.05) revision of the weight loss induced by Pb. Such gain in weight was significantly less than those observed in control animals during the course of study.
|Figure 1: Effects of heavy metal on body weight gain in rats treated with ginger|
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Effect of Zingiber officinale administration and heavy metal together on accumulation in the liver
The results of administration of Zingiber officinale, Hg, Cd and Pb concurrently on the accumulation of heavy metal in liver are presented in [Figure 2],[Figure 3] and [Figure 4]. The percentage protection offered differed when Zingiber officinale was ingested at the same time with the metals (group 2) as presented in [Table 2]. There was a significantly (P<0.01) higher percentage protection to Cd accumulation when compared to Hg and/or Pb at week two. However, the percentage protection to Cd accumulation was significantly (P<0.05) increased when compared with the other heavy metals at week 2. Zingiber officinale provided a significantly (P<0.05) highest protection to Cd accumulation at week 4 when compared to the protection to Hg and Pb metal. However, there was no level of protection to Pb observed at week 4. At week 6, the percentage protection to Hg and Cd accumulation in the liver was significantly (P<0.01) greater than protection to Pb. The percentage protection of Zingiber officinale at this period was significantly different in the three heavy metal groups. The summary of percentage protection offered by ginger to heavy metal accumulation in the liver is as follows: cadmium > mercury > lead.
|Table 2: Summary of percentage protection by ginger on heavy metal accumulation in the liver|
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Effect of one week administration of heavy metal before ginger on accumulation in the liver
The results of the effect of administration of heavy metal for one week before ginger supplementation on liver content of heavy metal are presented in [Figure 2],[Figure 3] and [Figure 4]. This is represented as group 3. There was a significant (P<0.01) increase in levels of protection by Zingiber officinale for cadmium when compared with lead and mercury [Table 2]. Zingiber officinale administration offered little or no protection to lead accumulation in the liver at week four whereas it reduces significantly (P<0.05) Hg and Cd accumulation by 50 and 60% respectively. However, the protection at week 6 offered by Zingiber officinale was significantly (P<0.01) higher in Cd-treated group (95%) when compared to Hg-treated (62%) and Pb-treated groups (0%). For this treatment protocol, Zingiber officinale treatment offered a highest protection to Cd accumulation in the liver when compared to Hg and Pb metals. There was no protection of Zingiber officinale to lead accumulation in the liver. The results show thatZingiber officinale offered the highest protection to Cd followed by Hg and least protection to Pb.
Effect of prior administration of ginger on heavy metal accumulation in liver
In the last protocol in which Zingiber officinale was given first to experimental animals before administration of the heavy metals ([Table 2], group 4), there was a significant (P<0.01) increase in protection to Pb (97%) and Cd (63%) accumulation when compared to Hg (32%) at week 2. The percentage protection offered by Zingiber officinale to accumulation of Pb and Cd in the liver was however significantly (P<0.01) decreased at week 4 when compared to week 2, though the value was significantly (P<0.05) increased in Hg-treated group. The percentage protection offered by Zingiber officinale at week 4 to Hg and Pb was comparable. At week 6, the percentage protection by Zingiber officinale to both Hg (44%) and Cd (85%) was significantly (P<0.01) different to each other while there was no protection to Pb (0%) at this period. On the whole, ginger offered the greatest protection to cadmium accumulation followed by Hg and least protection to Pb accumulation.
| Discussion|| |
The bioavailability and toxicity of heavy metals on animals is strongly influenced by the biology of the organism. This is because many organisms have developed some elimination methods that help to excrete even the assimilated quantities of the heavy metals. The kinetics of elimination and uptake of these chemicals/ metals from the body can display some unexpected patterns. , We would expect that under continuous exposure, there is a tendency for total internal body concentrations to increase as long as the animal is exposed to the metal, bearing in mind that these metals bioaccumulate and are not degradable. However, some researchers have reported an initial dramatic increase in accumulated heavy metals which then decreased even though animals were fed / exposed constantly to the metals. , Such reports had earlier been thought to be experimental or analytical errors but are now seen to have a biological basis. ,,, Our results also presented with such overshoots and non-conformity with expected patterns which can be attributed to the kinetics of the metal assimilation, uptake and excretion. According to Laskowski et al an animal may show a lag in physiological response that results in a delay in the onset of efficient elimination and/or decrease in metal assimilation following an exposure to high doses of these metals.
Chelation of these metals is an effective method of treatment of the metal-induced toxicity since it enhances the mobilization and excretion of metallic cations. ,, Nevertheless, there is increasing evidence suggesting that diet and/or metabolic differences may influence heavy metal uptake and/or excretion.  Nutrients are reported to affect bioavailability, toxico-dynamics, and transport to target organs, and influence the immunologic, biochemical, or cytologic functional responses to heavy metals. ,,
Zingiber officinale has been reported to act as an antitoxic agent , because of its rich antioxidant properties  which contribute to its free radical scavenging properties, a characteristic suited for metal chelation.  In our studies, we observed that Zingiber officinale offered some hepatic protection to heavy metal accumulations in the liver, such percentage protections varied with the metal and methodology of exposures.
Grzanna et al reported that Zingiber officinale modulates biochemical pathways activated in chronic inflammation, which may include its gastric protection, , chemopreventive and antioxidant potentials as well as a modulating effect on phase II detoxification enzyme and reduced glutathione.  All this may contribute to the kinetics of elimination of these metals from the system. Our observations were that Zingiber officinale had less percentage protection over Pb exposures. Protection offered to this metal accumulation was immediate but did not last with increase in durations of exposures. Protection offered to Hg and Cd exposures also showed a duration-dependent effect with initial and late increases at the second and sixth weeks but more to Cd than to Hg.
Also Zingiber officinale offered more protective ability through the elimination of Cd and Hg, but when given before exposure to the heavy metals, it significantly reduced the accumulation of Pb in the liver. After two weeks of treatment, Zingiber officinale did not offer any further protection to Pb exposures in all treatment groups. The results of the present study highlight the benefit of Zingiber officinale to be used as a nutrient supplement in heavy metal toxicity probably due to its antioxidant property.
Our studies focused on the accumulation, elimination and bioavailability of heavy metals following exposures and treatment with Zingiber officinale, a nutrient substance famed for its antioxidant and anti-inflammatory properties. We had earlier reported its hepatoprotection to cadmium-induced toxicity through amelioration of some liver enzymes.  In conclusion, Zingiber officinale affected the bioavailability, kinetics of the metal assimilation, uptake and excretion in a time-dependant manner, with more hepatic protection to Cd and less to Hg and Pb, as such it is beneficial for the reduction of heavy metal burden. Our results highlight the hepatoprotective effect of this nutrient substance against heavy metals, these hepatoprotective effects against other chemicals that induce hepatic stress and hepatotoxicity have been reported by other researchers ,,,,, and our studies further confirm it. Our limitations include the non-observance of the toxicokinetics of these metals due to treatment with the nutrient substances and the bioaccumulation of these metals in other tissues. There is a therefore need for further studies to investigate the effect of Zingiber officinale on heavy metal accumulation in other organs and its protective abilities through antioxidant assays.
| References|| |
|1.||Flora SJ, Pachauri V. Chelation in metal intoxication.Int J Environ Res Public Health 2010;7:2745-88. |
|2.||Valko M, Morris H, Cronin MT. Metals toxicity and oxidative stress.Curr Med Chem 2005;12:1161-208. |
|3.||Goyer RA, Bachmann J, Clarkson TW, Ferris BG Jr, Graham J, Mushak P, et al. Potential human health effects of acid rain: report of a workshop. Environ Health Perspect. 1985;60:355-68. |
|4.||Clarkson TW, Magos L, Myers GJ. The toxicology of mercury-current exposures and clinical manifestations. New Engl J Med 2003;349:1731-7. |
|5.||Silbergeld EK, Silva IA, Nyland JF. Mercury and autoimmunity: implications for occupational and environmental health. Toxicol Appl Pharmacol 2005;207:282-92. |
|6.||Houston MC. The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. Alt Therap Health Med 2007;13:S128-33. |
|7.||Geier DA, Sykes LK, Geier MR. A review of thimerosal (merthiolate) and its ethyl mercury breakdown product: specific historical considerations regarding safety and effectiveness. J Toxicol Environ Health B Crit Rev 2007;10:575-96. |
|8.||McGoldrick TA, Lock EA, Rodilla V, Hawksworth GM. Renal cysteine conjugate C-S lyase mediated toxicity of halogenated alkenes in primary cultures of human and rat proximal tubular cells. Arch Toxicol 2003;77:365-70. |
|9.||Horsfall MN, Spiff AI. Speciation of heavy metals in intertidal sediments of the Okirika river system (Nigeria). Bull Chem Soc Ethiopia 1999;13:1-9. |
|10.||Smolders E. Cadmium uptake by plants. Int J Occup Med Environ Health 2001;14:177-83. |
|11.||Misra RR, Hochadel JF, Smith GT, Cook JC, Waalkes MP, Wink DA. Evidence that nitric oxide enhancescadmium toxicity by displacing the metal from metallothionein. Chem Res Toxicol 1996;9:326-32. |
|12.||Jarup L. Hazards of heavy metal contamination. Brit Med Bull 2003;68:167-82. |
|13.||Klaassen CD, Liu J, Choudhuri S. Metallothionein: an intracellular protein to protect against cadmium toxicity. Ann Rev Pharmacol Toxicol 1999;39:267-94. |
|14.||Kelley C. Cadmium therapeutic agents.Curr Pharm Des 1999;5:229-40. |
|15.||Nordberg GF, Jin T, Wu X, Lu J, Chen L, Lei L, et al. Prevalence of kidney dysfunction in humans - relationship to cadmium dose, metallothionein, immunological and metabolic factors. Biochimie 2009;91:1282-5. |
|16.||Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001;1:529-39. |
|17.||Sandhir R, Gill KD. Effect of lead on lipid peroxidation in liver of rats.Biol Trace Elem Res 1995;48:91-7. |
|18.||Goyer RA. Toxic and essential metal interactions. Ann Rev Nutr 1997;17:37-50. |
|19.||Surh Y. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat Res 1999;428:305-27. |
|20.||Vimala S, Norhanom AW, Yadav M. Anti-tumor promoter activity in Malaysian ginger rhizome used in traditional medicine. Br J Cancer 1999;80:110-6. |
|21.||Sultana S, Ripa FA, Hamid K. Comparative antioxidant activity study of some commonly used spices in Bangladesh. Pak J Biol Sci 2010;13:340-3. |
|22.||Haleagrahara N, Jackie T, Chakravarthi S, Rao M, Kulur A. Protective effect of Etlingera elatior (torch ginger) extract on lead acetate--induced hepatotoxicity in rats. J Toxicol Sci 2010;35:663-71. |
|23.||Micklefield GH, Redeker Y, Meister V, Jung O, Greving I, May B. Effects of ginger on gastroduodenal motility. Int J Clin Pharmacol Ther 1999;37:341-6. |
|24.||Wu KL, Rayner CK, Chuah SK, Changchien CS, Lu SN, Chiu YC, Chiu KW, Lee CM. Effects of ginger on gastric emptying and motility in healthy humans. Eur J Gastroenterol Hepatol 2008;20:436-40. |
|25.||Tanabe M, Chen YD, Saito KI, Kano Y. Cholesterol Biosynthesis Inhibitory Component from Zingiber officinale Roscoe. Chem Pharm Bull (Tokyo) 1993;41:710-3. |
|26.||Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol 2005;97:227-30. |
|27.||Egwurugwu JN, Ufearo CS, Abanobi OC, Nwokocha CR, Duruibe JO, Adeleye GS, et al. Effects of ginger (Zingiber officinale) on cadmium toxicity. Afr J Biotechnol 2007;6:2078-82. |
|28.||Nwokocha CR, Owu DU, Ufearo CS, Iwuala MO. Comparative study on the efficacy of Garcinia kola in reducing some heavy metal accumulation in liver of Wistar rats. J Ethnopharmacol 2011;135:488-91. |
|29.||Nwokocha CR, Ejebe DE, Nwangwa EK, Ekene N, Akonoghrere R, Ukwu J. The effects of bitter kola supplemented diet on hepatotoxicity of mercury in Wistar rats. J Appl Sci Environ Manage 2010;14:89-95. |
|30.||Nwokocha CR, Nwokocha MI, Aneto I, Obi J, Udekweleze DC, Olatunde B, et al. Comparative analysis on the effect of Lycopersicon esculentum (tomato) in reducing cadmium, mercury and lead accumulation in liver. Food Chem Toxicol 2012;50:2070-73. |
|31.||Nwokocha, CR, Owu DU, Ufearo CS, Iwuala MOE. Comparative study on the efficacy of Allium sativum (garlic) in reducing some heavy metal accumulation in liver of wistar rats. Food Chem. Toxicol. 2012;50:222-26. |
|32.||Neuhauser EF, Cukik ZV, Malecki MR, Loehr RC, Durkin PR. Bioconcentration and biokinetics of heavy metals in the earthworm. Environ Pollut 1995;89:293-301. |
|33.||Laskowski R, Bednarska AJ, Spurgeon D, Svendsen C, van Gestel CA. Three-phase metal kinetics in terrestrial invertebrates exposed to high metal concentrations. Sci Total Environ 2010;408:3794-802. |
|34.||Descamps M, Fabre MC, Grelle C, Gerard S. Cadmium and lead kinetics during experimental contamination of the centipede Lithobius forficatus. L Arch Environ Contam Toxicol 1996;31:350- 3. |
|35.||Lagisz M, Kramarz P, Niklinska M. Metal kinetics and respiration rates in F1 generation of carabid beetles (Pterostichus oblongopunctatus F.) originating from metalcontaminated and reference areas. Arch Environ Contam Toxicol 2005;48:484-9. |
|36.||Spurgeon DJ, Hopkin SP. Comparisons of metal accumulation and excretion kinetics in earthworms (Eisenia fetida) exposed to contaminated field and laboratory soils. Appl Soil Ecol 1999;37:332-7. |
|37.||Graziano JH, Lolacono NJ, Moulton T, Mitchell ME, Slavkovich V, Zarate C. Controlled study of meso-2-3-dimercartosuccinic acid for the management of childhood lead intoxication. J Paed 1992;120:133-9. |
|38.||Canuel R, de Grosbois SB, Atikesse L, Lucotte M, Arp P, Ritchie C, et al. New evidence on variations of human body burden of methylmercury from fish consumption. Environ Health Persp 2006;114:302-6. |
|39.||Zalups RK, Ahmad S. Molecular handling of cadmium in transporting epithelia. Toxicol Appl Pharmacol 2003;186:163-88. |
|40.||Grzanna R, Lindmark L, Frondoza CG. Ginger; an herbal medicinal product with broad anti-inflammatory actions. J Med Food 2005;8:125-32. |
|41.||Suresh K, Manoharan S, Vijayaanand MA, Sugunadevi G. Chemopreventive and antioxidant efficacy of (6)-paradol in 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Pharmacol Rep 2010;62:1178-85. |
|42.||Sabina EP, Pragasam SJ, Kumar S, Rasool M. 6-Gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice. Zhong Xi Yi Jie He XueBao 2011;9:1264- 9. |
|43.||Atta AH, Elkoly TA, Mouneir SM, Kamel G, Alwabel NA, Zaher S. Hepatoprotective Effect of Methanol Extracts of Zingiber officinale and Cichoriumintybus. Indian J Pharm Sci 2010;72:564-70. |
|44.||Motawi TK, Hamed MA, Shabana MH, Hashem RM, Aboul Naser AF. Zingiber officinale acts as a nutraceutical agent against liver fibrosis. Nutr Metab (Lond) 2011;8:40. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]