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EXPERIMENTAL STUDY OF ANTIMONY INDUCED RENAL TOXICITY IN RABBITS.

Byline: MASUD K.U. AND NAGI A.H.

ABSTRACT

Background and Objectives: Contamination of the environment food and water with antimony com-pounds may affect human health through the persistent exposure to small doses over a long period. This study was carried out to demonstrate the dose related effects of antimony on renal tissues of rabbits.

Material and Methods: The study was carried out on 40 healthy rabbits weighing 1.5 kg average divi-ded into 4 groups each group having 10 animals with one control group. Group I animals were injected with antimony sodium tartrate of 1/2 MLD 6 mg/kg body weight I/V at interval of 2 days for 12 weeks. The experimental dose of 1.71 mg/kg body weight was injected I/V at interval of 4 days to group II ani-mals. Those of group III were injected 2ml of specific bovine albumin 30% (Dade USA) followed by sch-edule of group II animals. Group IV (control group) animals were injected I/V with distilled water. Ani-mals were sacrificed and renal biopsies were taken for microscopic evaluation of any pathological cha-nges.

Results and Conclusions: Main morphological changes were seen in proximal convoluted tubules and glomeruli (HandE PAS). A total of 10% glomeruli showed focal hypercelluarity of mesangial and endo-thelial cells increase in mesangial matrix leading to mesangial widening and vascular congestion alo-ng with protein casts. Mild to moderate degree of nephrocalcinosis was seen. On the other hand distal convoluted tubules did not reveal any change. This study indicated the toxic effects of antimony on renal tissue of rabbits predominantly involving the glomeruli with some degree of epithelial degeneration in the proximal convoluted tubules. Hyaline casts in the renal tubules were also prominent feature. It is concluded that the antimony has toxic effects on the renal tissue so preventive measures should be taken to avoid long term exposure in the industries and for therapeutic uses.

Key words: Antimony Renal cortex Glomeruli Rabbits Bovine Serum. INTRODUCTION

Effects of antimony on various organs of rats have been conventionally described by many authors.1-3 Man has always been exposed to heavy metals in the environment. Antimony is a major environmental tox-in due to its presence in air water food and soil.4 Anti-mony and its compounds are used in manufacturing of paints coatings rubbers insecticides colored printing inks and glass.5 Antimony toxicity occurs either due to occupational exposure or during therapy.6 Antimony has been mostly used for the treatment of leishma-niasis and schistosomiasis7. Metallic contamination of food and water lead to first incidence of metal toxi-city.89 In this study in addition to direct toxic effects of antimony its effects were also seen in immunologi-cally altered state of rabbits by injecting bovine albu-min at interval of 04 days for 12 weeks.

MATERIALS AND METHODS

This study was carried out on 40 healthy rabbits with average weight of 1.5 kg. They were housed individ-ually in well aerated metal cages at 26 28C room temperature. Their diet consisted of seasonal vegetab-les and grains. The antimony was used as Antimony sodium tar-trate NasbOC4H4O6 (BDH U.K). Its minimum lethal dose (MLD) was calculated as follows: MLD = 12 mg/kg. 1/2 MLD = 6 mg/kg. Experimental dose calculated for antimony as sodium tartrate = 1.71 mg/kg body weight. Stock solut-ion of antimony sodium tartrate 2% solution prepared by dissolving 1 gm antimony tartrate in 50ml of distil-led water. The rabbits were divided in 4 groups each group composed of 10 animals.

Group 1: Animals were given 1/2 MLD 6 mg/kg of antimony sodium tartrate I/V at interval of two days for 12 weeks.

Group II: Animals were injected with experimental dose of 1.71 mg/kg body weight of antimony sodium tartrate at interval of 4 days for 12 weeks.

Group III: Animals were injected I/V with 2.0 ml of

specific bovine albumin (30%) (DADE USA) followed by injections scheduled in group II.

Group IV (Control Group): Received only I/V in-jections of distilled water. All the animals were sacrificed at the end of expe-riment after 12 weeks by anaesthetizing them with ether. Kidneys were dissected out by giving midline in-cision on anterior abdominal wall. Capsule was gently stripped off. One of the kidney was cut longitudinally whereas other transversely and tissues were preserved in 10% formalin solutions. Sections were prepared and stains used included haematoxylin and eosin (HandE) Periodic acid Schiff (PAS) Methenamine silver (MS) and reticulin stain (RS).

RESULTS

Group I: On gross examination kidneys appeared

slightly smaller and rather pale with normal cortico medullary pattern. Microscopically 5 animals showed moderate deg-ree (++) of focal hypercelluarity of the mesangial cells in 10% of glomeruli. Basement membrane remained unremarkable on PAS and MSS. Seven animals showed vascular congestion in glo-meruli. Proximal convoluted tubules revealed mild degree (+) of granular degenerative changes in epithelial cells along with protein casts in three animals of group I. No change in distal convoluted tubule was seen. Five animals showed peripheral tubular focal ne-phrocalcinosis (mild to moderate degree). No remark-able change seen in interstitial stroma of any of the animals.

Group II Gross: kidneys are normal in size shape and colour with normal corticomedullary pattern. Microscopic examination of the 5 animals showed mild to moderate focal proliferation of mesangial cells and increase in mesangial matrix. 20% of glomerular capillaries showed marked con-gestion (+++). Five animal showed protein casts in proximal con-voluted tubules. Distal convoluted tubules revealed apoptosis and nephorocalcinosis. Extra glomerular blood vessels appeared normal except in 4 animals which showed vascular congestion sludging of RBCs with thrombus formation in small and medium sized blood vessels. No change was seen in interstitial stroma.

Group III Gross: Kidneys appeared slightly smaller pale with normal corticomedullary pattern. Microsco-pic examination showed mild focal mesangial cell pro-liferation. There was increase in amount of mesangial matrix in 3 animals with PAS positive material. No significant change in epithelial or endothelial cells of glomeruli was noted. There was severe degree of glomerular congestion in two animals. Protein filtrate seen in Bowman's space along-with sludging of RBC's in glomerular capillaries was obser-ved. Distal tubules showed protein casts and degenera-tive.

Group IV: Microscopically no significant change was seen in renal tissue. Kidneys were normal in size and shape with normal corticomedullary pattern.

DISCUSSION

Antimony sodium tartrate is a known toxic metal pre-sent in air water food and soil as well as in the manu-facturing of rubber glass paints coatings and colou-red printing inks.8 Antimony has now created environ-mental pollution due to increase in industrial applica-tions.9 The nephrotoxicity of antimony has been sugge-sted by many authors.10 As regards to therapeutic app-lication potassium antimony tartrate was put into use in the treatment of schistosomiasis and Leeishmani-asis.711 Most of the heavy metals are nephrotoxic par-ticularly causing tubular necrosis.12 It is known that even relatively low doses of a variety of metals can pro-duce various renal abnormalities.13 Chronic low level antimony exposure remains our major health problem especially in industrial workers; therefore current study was designed to evaluate the effects of antimony administration on structure and function of kidneys of rabbits. In this study rabbits were used as a mammalian model for studying as they are easily available and easy in handling. It is known that human and rabbits normally do not have detectable proteinuria.14 There-fore presence of significant quantities of urinary pro-teins is considered pathological.15 Microscopic examination of renal tissue revealed significant glomerular congestion which was seen of moderate to severe degree in 50% of animals of vari-ous groups. Among group I animals moderate degree (++) of focal hypercellularity of mesangial endothelial and epithelial cells were seen in most of glomeruli alo-ng with significant increase in mesangial matrix lead-ing to mesangial widening whereas in group II and III mild degree (+) of mesangial cell proliferation was seen with no significant change in endothelial and epi-thelial cells of glomeruli. One animal of group III reve-aled a renal infarction while no such change was seen in group I and II animals. The proximal convoluted tubules demonstrated granular degenerative changes of mild degree (+) in less than half of animals in group I II and III along with presence of protein casts. An interesting feature was the presence of focal nephrocalcinosis in animals of group I and II. Although not much experimental work has been carried out on antimony Maher16 repo-rted renal damage after antimony administration. Pati-ents treated with antimonials in high doses reported fatty degeneration of kidneys17 whereas no such cha-nge was observed in the present study.

It is concluded that antimony has proven to be toxic on the structure and function of renal tissue of rabbits. Based on the results of present study preven-tive measures should be taken to avoid the long term exposure in different industries and also when it is used for therapeutic purposes.

ACKNOWLEDGEMENTS

The authors are thankful to the administration of PG-MI Lahore to support this project.

REFERENCES

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2. Kale RM. Genotoxic effects of antimony on rat and mice. J Appl Toxicol. 2011; 25: 17-20.

3. Marc SB Gonzalez HP Obregon ER. Mechanisms of sel-ective action of heavy metal toxicity. A rev pharaqmcol Toxicol. 2012; 63: 321-327.

4. Doyle WH. Nutrional status of school children in an inner city area. Arch Dis Childhood. 1997; 70: 376-381.

5. Koutso PL Maravelias CF Koutselinis AJ. Immunologi- cal aspects of the common heavy metals Amaranth and Tartrezine. Hum Toxicol. 1998; 40: 11-24.

6. Flower CA. Antimony poisioning management. Chin toxicol Rev. 2009: 16-21.

7. Shahidi F. Chronic heavy metals toxicity studies in rats guinea pig and monkeys. Indian J Exp Biol. 2004; 83: 77-83.

8. Toxicological evaluation of some heavy metals. Rome: FAO / WHO. Food Agric. Org. of the United Nations and World Health Org. 2000: PP. 22-37.

9. Klaassen C.D. Heavy metals and heavy metal antago-nist. The pharmacological basis of therapeutics Good-man and Gilman (1985); 7th ed: PP. 1605-1627.10. Kale R.M. Genotoxic effects of antimony on rat and mice. JAPPAL. Toxico. 2011; 25: 17-20.

11. Dickerson O.B. Occupational medicine priniciples and practical applications published by year book Medical 1975 Chap. 29: 613-614.

12. Nagi A.H; Alenxander F. and Barabas A.Z. Gold Neph-ropathy in Rats. Light and electron microscopic studies exp. Mol. Pathol. 1971; 15: 354-362.

13. Hook J.B The basic science of poison Casarett and Doull's Toxicology 1980: P. 232-245.

14. Kozma C. Macklin W; Cummins L.M. Anatomy Phy-siology and biochemistry of rabbit; 1974: PP. 67-68.

15. Hardwicke J. Molecular size of IgG in patients with focal glumerulosclerosis. Clin. Nephrol. 1976; 6: 290.16. Meher J.F. Toxic Nephropathy. In Brenner B.M; and Rector F.C. Jr. (ed): The kidney W.B. Saunders Phila-delphia. 1976.

17. Klatskin G. Diseases of Liver. 1969; 3rd ed: P. 540-541
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Date:Sep 30, 2014
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