Journal of Animal Behaviour and Biometeorology
Journal of Animal Behaviour and Biometeorology
Research Article Open Access

Comprehension of the zinc chloride's ameliorative apoptotic and genotoxic effects on mice with cadmium-induced hepatotoxicity

Enas Nihad Bayram, Hanady S. Al-Shmgani, Nahla A. Al-Bakri

Downloads: 1
Views: 749


Cadmium is a typical heavy metal quite dangerous to humans and animals. Zinc supplementation protects the biological system from Cd toxicity and alleviates Cd-induced toxicity. The present study was assessed to evaluate the preventive effects of zinc chloride (ZnCl2) on male mice with liver damage induced by cadmium chloride (CdCl2). Metals accumulation was quantified in the liver. Body weight, liver weight ratio, lipid peroxidation, caspase 3, and DNA damage were determined in the liver of male mice after receiving an intraperitoneal (IP) a single dose of CdCl2 at 1.5 and 3 mg/kg or/and ZnCl2 10 mg/kg during 21 days. The LD50 was 6.023 mg/kg for CdCl2 and 89.05 mg/kg for ZnCl2.  The results indicate that mice in control and Zn groups gained body weight at the end of the experiment, while other treated groups significantly decreased. The relative weight of the liver revealed a significant increase in experimental groups. In addition, an increase in malondialdehyde level, Metallothionein concentration, and caspase-3 level was detected in Cd and Zn groups alone or in combination. Strand breaks of DNA of hepatocytes showed a significant increase in tail length of groups treated with cadmium. Co-treatment with zinc reduced these parameters compared to those measured in cells treated with cadmium. The outcome of this study implied that cadmium chloride causes oxidative stress, DNA damage, and elevated apoptosis markers in mice livers at low and medium doses. By pinpointing the target organ involved, the study results have also added some understanding of the impacts of zinc chloride injection to ameliorate cadmium toxicity in a low dose at 10 mg/kg.


cadmium toxicity, comet assay, oxidative liver markers, zinc protection


Al-Baqami NM and Hamza RZ (2021) Protective effect of resveratrol against hepatotoxicity of cadmium in male rats: antioxidant and histopathological approaches. Coatings11:594.

Ali HT (2012) Determination of the lethal dose 50%(LD50) of cadmium chloride and the histopathological changes in male mice liver and kidneys. Journal of Education and Science 25:27-38.

Banni M, Messaoudi I, Said L, El Heni, J, Kerkeni A, and Said K (2010) Metallothionein gene expression in liver of rats exposed to cadmium and supplemented with zinc and selenium. Archives of environmental contamination and toxicology 59:513-519.

Borowska S, Brzóska MM, Gałażyn-Sidorczuk M and Rogalska J (2017) Effect of an extract from Aronia melanocarpa L. berries on the body status of zinc and copper under chronic exposure to cadmium: An in vivo experimental study. Nutrients 9:1374.

Brzoska M, Borowska S, and Tomczyk M (2016) Antioxidants as a potential preventive and therapeutic strategy for cadmium. Current drug targets 17:1350-1384.

Brzoska M M, Rogalska J, and Kupraszewicz E (2011) The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: a study in a rat model of moderate and relatively high human exposure. Toxicology and applied pharmacology 250:327-335.

Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, Opdenakker K, Nair AR, Munters E, Artois TJ, Nawrot T, Vangronsveld J, Smeets K (2010) Cadmium stress: an oxidative challenge. Biometals 23:927-940.

Das SC and Al-Naemi HA (2019) Cadmium Toxicity: Oxidative Stress, Inflammation and Tissue Injury. Occupational Diseases and Environmental Medicine 17::144-163.

Gao P, Liu S, Ye W, Lin N, Meng P, Feng Y, Zhang Z, Cui F, Lu B, Xing B (2015) Assessment on the occupational exposure of urban public bus drivers to bioaccessible trace metals through resuspended fraction of settled bus dust. Science of The Total Environment 508:37-45.

Genchi G, Sinicropi MS, Lauria G, Carocci A and Catalano A (2020) The effects of cadmium toxicity. International journal of environmental research and public health 17:3782.

Guidet B. and Shah S V (1989) Enhanced in vivo H2O2 generation by rat kidney in glycerol-induced renal failure. American Journal of Physiology-Renal Physiology 257:440-445.                     

Isani G, Carpenè E (2014) Metallothioneins, unconventional proteins from unconventional animals: a long journey from nematodes to mammals. Biomolecules 22:435-57.

Jackson P, Pedersen LM, Kyjovska ZO, Jacobsen NR, Saber AT, Hougaard KS, Vogel U and Wallin H (2013) Validation of freezing tissues and cells for analysis of DNA strand break levels by comet assay 28:699-707.

Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65-87.

Klaassen C D, Liu J, Diwan B A (2009) Metallothionein protection of cadmium toxicity. Toxicology and applied pharmacology 238:215-220.

Kowaltowski AJ, de Souza-Pinto NC, Castilho RF, and Vercesi AE. (2009) Mitochondria and reactive oxygen species. Free Radical Biology and Medicine 47:333-343.

Liu J, Qu W, and Kadiiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicology and applied pharmacology 238:209-214.

Lossow K, Kopp JF, Schwarz M, Finke H, Winkelbeiner N, Renko K, Meçi X, Ott C, Alker W, Hackler J, Grune T, Schomburg L, Haase H, Schwerdtle T, Kipp AP (2020) Aging affects sex- and organ-specific trace element profiles in mice. Aging (Albany NY) 2:13762-13790.

Nilsson R, Liu NA (2020) Nuclear DNA damages generated by reactive oxygen molecules (ROS) under oxidative stress and their relevance to human cancers, including ionizing radiation-induced neoplasia part I: physical, chemical and molecular biology aspects. Radiation Medicine and Protection 1:140-152.

Nordberg GF, Jin T, Wu X, Lu J, Chen L, Lei L, Hong F, and Nordberg M (2009) Prevalence of kidney dysfunction in humans–relationship to cadmium dose, metallothionein, immunological and metabolic factors. Biochimie 91:1282-1285.

Pałka SE, Drąg-Kozak E, Migdał L, Kmiecik M (2022) Effect of a Diet Supplemented with Nettle (Urtica dioica L.) or Fenugreek (Trigonella Foenum-Graecum L.) on the Content of Selected Heavy Metals in Liver and Rabbit Meat. Animals 12:827.

Patra RC, Rautray AK, and Swarup D (2011) Oxidative stress in lead and cadmium toxicity and its amelioration. Vet Med Int. 2011 Mar 20:457327.

Permyakov EA (2021) Metal Binding Proteins. Encyclopedia 1:261-292.

Poli V, Madduru R, Aparna Y, Kandukuri V, Motireddy SR (2022) Amelioration of Cadmium-Induced Oxidative Damage in Wistar Rats by Vitamin C, Zinc and N-Acetylcysteine. Medical Sciences 10:7.

Powell SR (2000) Zinc and Health: Current Status and Future Directions-Session IV. Zinc and Cellular Mechanisms-The Antioxidant Properties of Zinc. Journal of Nutrition 130:1488-1492.

Rahimzadeh MR, Rahimzadeh MR, Kazemi S, Moghadamnia AA (2017) Cadmium toxicity and treatment: An update. Caspian journal of internal medicine 8:135.

Richards MP, Steele NC (1987) Isolation and quantitation of metallothionein isoforms using reversed-phase high-performance liquid chromatography. Journal of Chromatography A 402:243-256.

Rogalska J, Pilat-Marcinkiewicz B, Brzóska MM (2011) Protective effect of zinc against cadmium hepatotoxicity depends on this bioelement intake and level of cadmium exposure: a study in a rat model. Chemico-Biological Interactions 193:191-203.

Samir D, Zine K (2013) Preventive effect of zinc on nickel-induced oxidative liver injury in rats. African Journal of Biotechnology 12:7112-7119.

Skipper A, Sims JN, Yedjou CG, Tchounwou PB (2016) Cadmium chloride induces DNA damage and apoptosis of human liver carcinoma cells via oxidative stress. International journal of environmental research and public health 13:88.

Smith MA, Schnellmann RG (2012) Calpains, mitochondria, and apoptosis. Cardiovasc 96:32-7.

Stanevieiene I, Sadauskiene I, Lesauskaite V, Ivanoviene L, Kaðauskas A, Ivanov L (2008) Subacute effects of cadmium and zinc ions on protein synthesis and cell death in mouse liver. Medicina 44:131.

Tang L, Qiu R, Tang Y and Wang S (2014) Cadmium-zinc exchange and their binary relationship in the structure of Zn-related proteins: a mini review. Metallomics 6:1313-1323.

Thevenod F, Lee WK (2013) Toxicology of Cadmium and Its Damage to Mammalian Organs. In: Sigel, A., Sigel, H., Sigel, R. (eds) Cadmium: From Toxicity to Essentiality. Metal Ions in Life Sciences. Springer, Dordrecht, pp. 415-490.

Vasak M, Meloni G (2011) Chemistry and biology of mammalian metallothioneins. JBIC Journal of Biological Inorganic Chemistry 16:1067-1078.                                                              

Waalkes MP (2003) Cadmium carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 533:107-120.

Zhou Z, Wang C, Liu H, Huang Q, Wang M, Lei Y (2013) Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells. Int J Med Sci. 10:1485-96.

Submitted date:

Reviewed date:

Accepted date:

6323d102a9539539e9150ff2 jabbnet Articles
Links & Downloads

J. Anim. Behav. Biometeorol.

Share this page
Page Sections