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The protective role of ascorbic acid in the hepatotoxicity of cadmium and mercury in rabbits

  • Shumaila Mumtaz
  • Shaukat AliEmail author
  • Rida Khan
  • Saiqa Andleeb
  • Mazhar Ulhaq
  • Muhammad Adeeb Khan
  • Hafiz Abdullah Shakir
Research Article
  • 59 Downloads

Abstract

The liver is one of the vital and sensitive organs which are usually exposed against the toxicity of mercury (Hg) and cadmium (Cd). The main objective of the current study was to evaluate the potential toxicological effects of both Cd and Hg as individual and combined. Hepatotoxicity was evaluated by monitoring the biochemical parameters of the liver and their accumulation in the liver as well as therapeutic role of vitamin C in said toxicity in rabbits (Oryctolagus cuniculus). In this research, cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to treatment groups of the rabbits for 28 alternative days. Various biochemical parameters of the liver such as lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), bilirubin, alanine aminotransferase (ALAT), total protein, and gamma glutamyl transferase (GGT) were estimated using blood samples. Some biochemical parameters like ASAT, ALAT, LDH, GGT, and bilirubin were significantly elevated (P ≤ 0.001) in individual Cd and Hg treatment groups, while the level of total protein was found to be significantly declined. The effects of Cd and Hg in the presence of vitamin C on these biochemical parameters were low as compared to metals-treated groups. Similar results were found when rabbits were treated with co-administration of both metals and vitamin C. Accumulation of Cd and Hg found to be higher in the liver. However, chemoprevention and chemotreatment with vitamin C significantly (P ≤ 0.01) minimized the toxicological effects of both metals but not regained the accumulation similar to that of the control group. The findings of this study provide awareness on accumulation of metals in the liver in rabbits and their toxicity tested through biochemical parameters as well as the therapeutic role of vitamin C in such alterations.

Keywords

CdCl2 HgCl2 Vitamin C Toxicity Metal accumulation Liver 

Notes

References

  1. Acharya UR, Mishra M, Patro J, Panda MK (2008) Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium. Reprod Toxicol 25(1):84–88Google Scholar
  2. Agarwal R, Raisuddin S, Tewari S, Goel SK, Raizada RB, Behari JR (2010) Evaluation of comparative effect of pre- and posttreatment of selenium on mercury-induced oxidative stress, histological alterations, and metallothionein mRNA expression in rats. J Biochem Mol Toxicol 24(2):123–135Google Scholar
  3. Ali S, Hussain S, Khan R, Mumtaz S, Ashraf N, Andleeb S, Shakir HA, Tahir HM, MKA K, Ulhaq M (2019) Renal toxicity of heavy metals (cadmium and mercury) and their amelioration with ascorbic acid in rabbits. Environ Sci Pollut Res Int 26:3909–3920Google Scholar
  4. Baselt RC, Cravey RH (2000) Disposition of toxic drugs and chemicals in man, 4th edn. Year Book Medical Publishers, Chicago, IL, pp 105–107Google Scholar
  5. Bashandy SA, Alhazza IM, El-Desoky GE, Al-Othman ZA (2011) Hepatoprotective and hypolipidemic effects of Spirulina platensis in rats administered mercuric chloride. Afr J Pharm Pharmacol 5(2):175–182Google Scholar
  6. Bernard A (2008) Cadmium & its adverse effects on human health. Indian J Med Res 128(4):557–564Google Scholar
  7. Birch RJ, Bigler J, Rogers JW, Zhuang Y, Clickner RP (2014) Trends in blood mercury concentrations and fish consumption among US women of reproductive age, NHANES, 1999–2010. Environ Res 133:431–438Google Scholar
  8. Caito S, Aschner M (2015) Neurotoxicity of metals. ClinNeurol 131(2):169–189Google Scholar
  9. Castagnetto JM, Hennessy SW, Roberts VA, Getzoff ED, Tainer JA, Pique ME (2002) MDB: the metalloprotein database and browser at the Scripps Research Institute. Nucleic Acids Res 30(1):379–382Google Scholar
  10. Chang HJ, Park JS, Lee EK, Kim MH, Baek MK, Kim HR, Jeong HG, Choi SY, Jung DY (2009) Ascorbic acid suppresses the 2, 3, 7, 8-tetrachloridibenxo-p-dioxin (TCDD)-induced CYP1A1 expression in human HepG2 cells. Toxicol In Vitro 23(4):622–626Google Scholar
  11. Chibunda R, Janssen C (2009) Mercury residues in free-grazing cattle and domestic fowl form the artisanal gold mining area of Geita district, Tanzania. Food Addit Contam 26(11):1482–1487Google Scholar
  12. Dardouri K, Haouem S, Gharbi I, Sriha B, Haouas Z, El Hani A, Hammami M (2016) Combined effects of Cd and Hg on liver and kidney histology and function in wistar rats. J Agr Chem Environ 5(04):159Google Scholar
  13. Delraso NJ, Foy B, Gearhart J, Frazier J (2003) Cadmium uptake kinetics in rat hepatocytes: correction for albumin binding. Toxicol Sci 72(1):19–30Google Scholar
  14. Du Preez H, Steyn G (1992) A preliminary investigation of the concentration of selected metals in the tissues and organs of the tigerfish (Hydrocynus Vit Ctatus) from the Olifants River, Kruger National Park, South Africa. Water SA 18(2):131–136Google Scholar
  15. El-Demerdash F, Yousef M, Elagamy E (2001) Influence of paraquat, glyphosate, and cadmium on the activity of some serum enzymes and protein electrophoretic behavior (in vitro). J Environ Sci Health Part B 36(1):29–42Google Scholar
  16. El-Sokkary GH, Awadalla EA (2011) The protective role of vitamin C against cerebral and pulmonary damage induced by cadmium chloride in male adult albino rat. The Neuroendocrinol J 4(1):20–30Google Scholar
  17. Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 1(6):529–539Google Scholar
  18. Fujishiro H, Okugaki S, Kubota K, Fujiyama T, Miyataka H, Himeno S (2009) The role of ZIP8 down-regulation in cadmium-resistant metallothionein-null cells. J Appl Toxicol 29(5):367–373Google Scholar
  19. Gajawat S, Sancheti G, Goyal P (2005) Vitamin C against concomitant exposure to heavy metal and radiation: a study on variations in hepatic cellular counts. Asian J Exp Sci 19(2):53–58Google Scholar
  20. Genchi G, Sinicropi MS, Carocci A, Lauria G, Catalano A (2017) Mercury exposure and heart diseases. Int J Environ Res Public Health 14(1):74Google Scholar
  21. Ghosh N, Bhattacharya S (1992) Thyrotoxicity of the chlorides of cadmium and mercury in rabbit. Biomed Environ Sci 5(3):236–240Google Scholar
  22. Heinrich J, Guo F, Trepka MJ (2017) Brief report: low-level mercury exposure and risk of asthma in school-age children. Epidemiology 28(1):116–118Google Scholar
  23. Henry RJ (1964) Colorimetric determination of total protein: clinical Chemistry. Harper and Row, New York, pp 181–183Google Scholar
  24. Hosseini A, Rajabian A, Fanoudi S, Farzadnia M, Boroushaki MT (2018) Protective effect of Rheum turkestanicum root against mercuric chloride-induced hepatorenal toxicity in rats. J Phytomed 8(6):488–491Google Scholar
  25. Hounkpatin A, Johnson R, Guedenon P, Domingo E, Alimba C, Boko M, Edorh P (2012) Protective effects of vitamin C on haematological parameters in intoxicated wistar rats with cadmium, mercury and combined cadmium and mercury. Int Res J Biol Sci 1(8):76–81Google Scholar
  26. Huq M, Awal M, Mostofa M, Ghosh A, Das A (2013) Effects of vitamin E and vitamin C on Mercury induced toxicity in mice. Progress Agric 19(2):93–100Google Scholar
  27. Imed M, Fatima H, Abdelhamid K (2008) Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the liver and kidney of the rat: histology and Cd accumulation. Food Chem Toxicol 46(11):3522–3527Google Scholar
  28. Jagadeesan G, Pillai SS (2007) Hepatoprotective effects of taurine against mercury induced toxicity in rat. J Environ Biol 28(4):753–756Google Scholar
  29. Joshi D, Mittal DK, Shukla S, Srivastav AK (2012) Therapeutic potential of N-acetyl cysteine with antioxidants (Zn and Se) supplementation against dimethyl mercury toxicity in male albino rats. Exp Toxicol Pathol 64(1):103–108Google Scholar
  30. Josthna P, Geetharathan T, Sujatha P, Deepika G (2012) Accumulation of lead and cadmium in the organs and tissues of albino rat. Int J Pharm Sci 3(12):114–128Google Scholar
  31. Kampalath RA, Jay JA (2015) Sources of mercury exposure to children in low-and middle-income countries. J Health Pollu 5(8):33–51Google Scholar
  32. Kaur S, Sharma S (2017) A histometric study to assess preventive action of ascorbic acid and garlic on cadmium induced hepatotoxicity in albino mice. Int J Pharm Phytopharmacol Res 23:5(3):8–14Google Scholar
  33. Kim KA, Lee WK, Kim JK, Seo MS, Lim Y, Lee Y (2001) Mechanism of refractory ceramic bre and rock wool induced cytotoxicity in alveolar macrophages. Int. Arch. Occup Environ Health 74:9–15Google Scholar
  34. Koyu A, Gokcimen A, Ozguner F, Bayram DS, Kocak A (2006) Evaluation of the effects of cadmium on rat liver. Mol Cell Biochem 284(1):81–85Google Scholar
  35. Malloy HT, Evelyn KA (1937) The determination of bilirubin with the photometric colorimeter. J Biol Chem 119:481–490Google Scholar
  36. Martin S, Griswold W (2009) Human health effects of heavy metals. Sci Technol Brief Cit 15:1–6Google Scholar
  37. Musa SA, Omoniye IM, Hamman WO, Ibegbu AO, Umana UE (2012) Preventive activity of ascorbic acid on lead acetate induced cerebellar damaged in adult wistar rats. Med Health Sci J 13:99–104Google Scholar
  38. Mutlu A, Lee BK, Park GH, Yu BG, Lee CH (2012) Long-term concentrations of airborne cadmium in metropolitan cities in Korea and potential health risks. Atmospheric Environ 47:164–173Google Scholar
  39. Naito HK, David JA (1984) Laboratory considerations: determination of cholesterol, triglyceride, phospholipid, and other lipids in blood and tissues. Lab Res Methods Biol Med 10(2):1–7Google Scholar
  40. Nathwani RA, Pais S, Reynolds TB, Kaplowitz N (2005) Serum alanine aminotransferase in skeletal muscle diseases. Hepatol 41(2):380–382Google Scholar
  41. Nithya NK, Chandrakumar VG, Senthilkumar S (2012) Efficacy of Momordica charantia in attenuating hepatic abnormalities in cyclophosphamide intoxicated rats. J Pharmacol Toxicol 7(1):38–45Google Scholar
  42. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M (2004) Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140(7):533–537Google Scholar
  43. Rana T, Bera AK, Das S, Pan D, Bandyopadhyay S, Bhattacharya D, De S, Sikdar S, Das SK (2010) Effect of ascorbic acid on blood oxidative stress in experimental chronic arsenicosis in rodents. Food Chem Toxicol 48(4):1072–1077Google Scholar
  44. Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28(1):56–63Google Scholar
  45. Renugadevi J, Prabu SM (2010) Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxicol Pathol 62(2):171–181Google Scholar
  46. Rosalki SB, Rav D, Lchman D, Prentice M (1970) Determination of serum gamma-glutamyl transpeptidase activity and its clinical applications. Ann Clin Biochem 7:143–147Google Scholar
  47. Sakamoto M, Man Chan H, Domingo JL, Kubota M, Murata K (2012) Changes in body burden of mercury, lead, arsenic, cadmium and selenium in infants during early lactation in comparison with placental transfer. Ecotoxicol Environ Saf 84:179–184Google Scholar
  48. Sweety R, Mathan RR, Kenneth S, Sajwan K (2008) Influence of zinc on cadmium induced haematological and biochemical responses in a freshwater teleost fish Catlacatla. Fish Physiol Biochem 34:169–174Google Scholar
  49. Tay CK, Asmah R, Biney CA (2010) Trace metal levels in water and sediment from the Sakumo II and Muni Lagoons, Ghana. West Afr J App Ecol 16(1):75–94Google Scholar
  50. Thapa B, Walia A (2007) Liver function tests and their interpretation. Indian J Pediatr 74(7):663–671Google Scholar
  51. Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicol 192(2):95–117Google Scholar
  52. Yannai S, Berdicevsky I, Duek L (1991) Transformations of inorganic mercury by Candida albicans and Saccharomyces cerevisiae. Appl Environ Microbiol 57(1):245–247Google Scholar
  53. Yazihan N, Kocak MK, Akcil E, Billur D, Ermis E, Cesaretli Y, Erdem O, Uzunalimoglu O (2015) Chronic cadmium toxicity induces inflammation and galectin-3 expression whereas suppresses the hypoxia inducible factor mRNA expression in the liver. Trace Elem 32:1–10Google Scholar
  54. Yousafzai AM, Shakoori AR (2008) Heavy metal accumulation in gills of an endangered South Asian freshwater fish as an indicator of aquatic pollution. Pak J Zoo 40(6):423–430Google Scholar
  55. Yu X, Sidhu JS, Hong SW, Robinson JF, Ponce RA, Faustman EM (2011) Cadmium induced p53 dependent activation of stress signaling, accumulation of ubiquitinated proteins and apoptosis in mouse embryonic fibroblast cells. Toxicol Sci 3(2):1–10Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Shumaila Mumtaz
    • 1
  • Shaukat Ali
    • 2
    Email author
  • Rida Khan
    • 1
  • Saiqa Andleeb
    • 1
  • Mazhar Ulhaq
    • 3
  • Muhammad Adeeb Khan
    • 1
  • Hafiz Abdullah Shakir
    • 4
  1. 1.Department of ZoologyThe University of Azad Jammu and KashmirMuzaffarabadPakistan
  2. 2.Department of ZoologyGovernment College UniversityLahorePakistan
  3. 3.Department of Veterinary Biomedical SciencesPMAS Arid Agriculture UniversityRawalpindiPakistan
  4. 4.Department of ZoologyUniversity of the PunjabLahorePakistan

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