Toxicology International (Formerly Indian Journal of Toxicology)

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Manganese Chloride Induced Hepatic and Renal Toxicity in Wistar Rats


Affiliations
1 Department of Zoology, Centre for Advance Studies, University of Rajasthan, Jaipur, India
     

   Subscribe/Renew Journal


Manganese (Mn) is an essential trace metal and acts as cofactor in many cellular enzymes. But excessive concentration of the Mn is potentially toxic resulting in several disorders. The present study was designed to evaluate toxic effects of manganese chloride (MnCl2.4H2O) exposure on marker biochemical parameters, antioxidant defense system and histomorphology of liver and kidney in rats. Adult male Wistar rats were randomly divided into three groups. In group A, the rats were treated with vehicle (0.5 ml normal saline) and served as control. The rats in group B and C were exposed to MnCl2 (50 and 100 mg/kg b.wt./day, p.o. respectively) for 120 days. The results showed significant elevation in cholesterol and triglyceride contents in liver while glycogen concentration showed significant depletion. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, urea and creatinine were significantly increased by MnCl2 treatment. The present data also indicated that MnCl2 significantly increased lipid peroxidation (LPO) and concomitantly decreased the levels of glutathione (GSH), ascorbic acid and superoxide dismutase (SOD) activity in both liver and kidney extracts compared to control. Histopathological study of the liver of MnCl2 exposed rats showed dose based degenerative and atrophic changes, infiltration of mononuclear cells and dilation of sinusoids. Sections of kidney also showed dilation of glomeruli and degenerative changes in the tubules. Taken together these data suggest that MnCl2 exposure has adverse impact on the morphology and functions of both liver and kidney in rats.

Keywords

Histopathology, Kidney, Lipid Peroxidation, Liver, Manganese Chloride.
User
Subscription Login to verify subscription
Notifications
Font Size

  • Keen CL, Ensunsa JL, Watson MH, Baly DM, Donovan SM, Monaco MH et al. Nutritional aspects of manganese from experimental studies. Neurotoxicol 1999; 20: 213-23.

  • Saric M. Manganese. In: Friberg L, Nordberg GF and Vouk V, editors. Handbook on the toxicology of metals. 2nd edn. Amsterdam: Elsevier Science Publishers; 1986. pp 354-86

  • Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Manganese. Atlanta: US Department of Health and Human Services, Public Health Service; 2000.

  • Sanatamaria AB. Manganese exposure, essentiality and toxicity. Indian J Med Res 2008; 128: 484-500.

  • Butterworth RF. Metal toxicity liver disease and neurodegeneration. Neurotox Res 2010; 18: 100-5.

  • Liccione JJ and Maines MD. Selective vulnerability of glutathione metabolism and cellular defense mechanisms in rat striatum to manganese. J Pharmacol Exp Ther 1988; 247: 156-61.

  • Zhang S, Zhou Z and Fu J. Effect of manganese chloride exposure on liver and brain mitochondria function in rats. Environ Res 2003; 93:149-57.

  • Parenti M, Rusconi K, Cappabianca W, Parati EA and Groppetti A. Role of dopamine in manganese toxicity. Brain Res 1988; 473: 236-40.

  • Zheng W, Zhao Q, Slavkovich V, Aschner M and Graziano JH. Alteration of iron homeostasis following chronic exposure to manganese in rats. Brain Res 1999; 833: 125-32.

  • Chen MT, Cheng GW, Lin CC, Chen BH and Huang YL. Effects of acute manganese chloride exposure on lipid peroxidation and alteration of trace metals in rat brain. Biol Trace Elem Res 2006; 110: 163-78.

  • Crossgrove J and W Zheng. Manganese toxicity upon overexposure. NMR in Biomed 2004; 17: 544-53.

  • Jiang Y and Zheng W. Cardiovascular toxicities upon manganese exposure. Cardiovasc Toxicol 2005; 5: 345-54.

  • Laskey JW, Rehnberg JF and Hein JF. Effects of chronic manganese exposure on selected reproductive parameters. J Toxicol Environ Health1982; 9: 677-87.

  • Sanchez DJ, Domingo JL, Llobet JM and Keen CL. Maternal and developmental toxicity of manganese in the mouse. Toxicol Lett 1993; 69: 45-52.

  • Wirth JJ, Rossano MG, Daly DC, Puscheck E, Potter RC and Diamond MP. Manganese exposure is negatively associated with human sperm motility and concentration. Epidemiology 2007; 18: 270-73.

  • Chandel M and Jain GC. Toxic effects of transition metals on male reproductive system: a review. J Environ Occup Sci 2014; 3: 204-13.

  • Shukla GS and Chandra SV. Concurrent exposure to lead, manganese, and cadmium and their distribution to various brain regions, liver, kidney, and testis of growing rats. Arch Environ Con Tox 1987; 16: 303-10.

  • Dorman DC, Struve MF, Marshall MW, Parkinson CU, James RA and Wong BA. Tissue manganese concentrations in young male rhesus monkeys following subchronic manganese sulfate inhalation. Toxicol Sci 2006; 92: 201-10.

  • Khan KN, Andress JM and Smith PF. Toxicity of subacute intravenous manganese chloride administration in beagle dogs. Toxicol Pathol 1997; 25: 344-50.

  • Huang P, Chen C, Wang H, Li G, Jing H, Han Y et al. Manganese effects in the liver following subacute or subchronic manganese chloride exposure in rats. Ecotoxicol Environ Saf 2011; 74: 615-622.

  • Nuha and AL-Harbi Y. Histological alteration induced by manganese chloride in the male testes, epididymis and kidney of the albino rats. IOSR-JPBS 2014; 3: 12-9.

  • Zlatkis A, Zak B and Boyal AJ. A new method for direct determination of cholesterol. J Clin Med 1953; 41: 486-9.

  • Gottfried SP and Rosenberg B. Improved manual spectrophotometric procedure for determination of serum triglycerides. Clin Chem 1973; 19: 1077-8.

  • Montogomery R. Determination of glycogen. Arch Biochem Biophys 1957; 67: 378-89.

  • Ohkawa H, Ohishi N and Yagi K. Assay for lipid peroxide formation in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-8.

  • Marklund S and Marklund G. Involvement of superoxide radical in the auto oxidation pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974; 7: 46974.

  • Moron MJ, Depieare JW and Mannivik B. Leaves of glutathione reductase and glutathione transferase activities in rat lung and liver. Biochem Biophys Act 1979; 582: 67-8.

  • Roe JH and Kuether CA. Determination of ascorbic acid in whole blood and urine through the 2,4-DNPH derivative of dehydroascorbic acid. J Biol Chem 1943; 147: 399-407.

  • Lowry OH, Oser MJ and Randoll RJ. Protein measurement with the folin phenol reagents. J Biol Chem 1951; 193: 26575.

  • Misselwitz B, Mhhler A and Weinmann H. The toxicologic risk for using manganese complexes? A literature survey of existing data through several medical specialities. Invest Radiol 1995; 30: 611-620.

  • Pandey G, Jain GC and Mathur N. The effect of sub chronic exposure to ammonium molybdate on hematological and hepatic parameters in albino rats. AJPBR 2012; 2: 136-42.

  • Klimis-Tavantzis DJ, Taylor PN and Wolinsky I. Manganese, Lipid Metabolism and Atherosclerosis. In: Klimis-Tavantzis DJ, editor. Manganese in Health and Disease. CRC press inc; 1994. pp: 87-100.

  • Nath K and Kumar N. Toxicity of manganese and its impact on some aspects of carbohydrate metabolism of a freshwater teleost, Colisa fasciatus. Sci Total Environ 1987; 76: 25762.

  • Baly DL, Lo¨nnerdal B and Keen CL. Effects of high doses of manganese on carbohydrate homeostasis. Toxicol Lett 1985; 25: 95-102.

  • Malthankar GV, White BK, Bhushan A, Daniels CK, Rodnick KJ and Lai JC. Differential lowering by manganese treatment of activities of glycolytic and tricarboxylic acid (TCA) cycle enzymes investigated in neuroblastoma and astrocytoma cells is associated with manganese-induced cell death. Neurochem Res 2004; 29: 709-17.

  • Sherlock S and Dolley JS. Assessment of liver function. In: Dooley JS, Lok ASF, Burroughs AK and Heathcote EJ, editor. Sherlock’s diseases of the liver and biliary syste. 12th edition. UK: Wiley Blackwell Publication; 2011. pp 20-35.

  • Sallie R, Tredger JM and Williams R. Drugs and the liver. Part 1: Liver testing function. Biopharm Drug Dipos 1991; 12: 251-9.

  • Salehi F, Krewski D, Mergler D, Normandin L, Kennedy G, Philippe, S et al. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in sprague-dawley rats following subchronic (90 days) inhalation exposure. Toxicol Appl Pharmacol 2003; 191: 264–71.

  • Ayotte P and Plaa GL. Biliary excretion in Sprague-Dawley and Gunn rats during manganese-bilirubin-induced cholestasis. Hepatology 1988; 8: 1069-78.

  • El-Shenawy SMA and Hassan NS. Comparative evaluation of the protective effect of selenium and garlic against liver and kidney damage induced by mercury chloride in the rats. Pharmacol Rep 2008; 60: 190-208.

  • Rosner MH and Bolton WK. Renal function testing. Am J Kidney Dis 2006; 47: 174-83.

  • Syed EA, Helen MD, Glenn DN, George WL and William JS. Manganese induced reactive oxygen species: comparison between Mn+2 and Mn +3. Neurodegeneration 1995; 4: 329-34.

  • Milatovic D, Gupta RC, Yu Y, Zaja-Milatovic S, and Aschner M. Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury. Toxicol Appl Pharmacol 2011; 256: 219-26.

  • Stohs SJ and Bagchi D. Oxidative mechanism in the toxicity of metal ions. Free Radic Biol Med 1995; 18: 321-36.

  • Poli G, Schaur RJ, Siems WG and Leonarduzzi G. 4-Hydroxynonenal: A membrane lipid oxidation product of medicinal interest. Med Res Rev 2008; 28: 569-631.

  • Lebda MA, El-Neweshy MS and El-Sayed YS. Neurohepatic toxicity of subacute manganese chloride exposure and potential chemoprotective effects of lycopene. NeuroToxicol 2012; 33: 98-110.

  • Huang P, Li G, Chen C, Wang H, Han Y, Zhang S, et al. Differential toxicity of Mn2+ and Mn3+ to rat liver tissues: oxidative damage membrane fluidity and histopathological changes. Exp Toxicol Pathol 2012; 64: 197-203.

  • Lushchak VI. Glutathione homeostasis and functions: potential targets for medical interventions J Amino Acids 2012; Article ID 736837.

  • Wu G, Fang YZ, Yang S, Lupton JR and Turner ND. Glutathione metabolism and its implications for health. J Nutr 2004; 134:489-92.

  • Kumar A, Rahal A, Zoheb SM, Prakash A and Mandil R. Antioxidant role of ascorbic acid on oxidative stress induced by sub-acute exposure of lead and cypermethrin in erythrocytes of wistar rats. Toxicol Environ Chem 2015; 96: 1248-59.

  • Brzoska MM, Moniuszko-Jakoniuk J, Pilat-Marcinkiewicz B and Sawicki B. Liver and kidney function and histology in rats exposed to cadmium and ethanol. Alcohol Alcohol 2003; 38: 2-10.

  • Missoun F, Slimani M and Aoues A. Toxic effect of lead on kidney function in rat Wistar. Afr J Biochem Res 2010; 4: 21-7.

  • Agarwal R, Goel SK and Behari JR. Detoxification and antioxidant effects of curcumin in rats experimentally exposed to mercury. J Appl Toxicol 2010; 30: 457-68.

  • Orrenius S, Gogvadze V and Zhivotovsky B. Mitochondrial oxidative stress: implications for cell death. Annu Rev Pharmacol Toxicol 2007; 47: 143-183.


Abstract Views: 631

PDF Views: 0




  • Manganese Chloride Induced Hepatic and Renal Toxicity in Wistar Rats

Abstract Views: 631  |  PDF Views: 0

Authors

Milan Chandel
Department of Zoology, Centre for Advance Studies, University of Rajasthan, Jaipur, India
G. C. Jain
Department of Zoology, Centre for Advance Studies, University of Rajasthan, Jaipur, India

Abstract


Manganese (Mn) is an essential trace metal and acts as cofactor in many cellular enzymes. But excessive concentration of the Mn is potentially toxic resulting in several disorders. The present study was designed to evaluate toxic effects of manganese chloride (MnCl2.4H2O) exposure on marker biochemical parameters, antioxidant defense system and histomorphology of liver and kidney in rats. Adult male Wistar rats were randomly divided into three groups. In group A, the rats were treated with vehicle (0.5 ml normal saline) and served as control. The rats in group B and C were exposed to MnCl2 (50 and 100 mg/kg b.wt./day, p.o. respectively) for 120 days. The results showed significant elevation in cholesterol and triglyceride contents in liver while glycogen concentration showed significant depletion. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, urea and creatinine were significantly increased by MnCl2 treatment. The present data also indicated that MnCl2 significantly increased lipid peroxidation (LPO) and concomitantly decreased the levels of glutathione (GSH), ascorbic acid and superoxide dismutase (SOD) activity in both liver and kidney extracts compared to control. Histopathological study of the liver of MnCl2 exposed rats showed dose based degenerative and atrophic changes, infiltration of mononuclear cells and dilation of sinusoids. Sections of kidney also showed dilation of glomeruli and degenerative changes in the tubules. Taken together these data suggest that MnCl2 exposure has adverse impact on the morphology and functions of both liver and kidney in rats.

Keywords


Histopathology, Kidney, Lipid Peroxidation, Liver, Manganese Chloride.

References





DOI: https://doi.org/10.22506/ti%2F2016%2Fv23%2Fi3%2F146713