Original Article

Biochemical Evaluation of The Effects of Vitamin C in Rats Exposed to Sub-Chronic Low Doses of Cadmium

A Omonkhua, F Obi

Keywords

alkaline phosphatase, bone, cadmium, calcium, kidney, phosphate, vitamin c

Citation

A Omonkhua, F Obi. Biochemical Evaluation of The Effects of Vitamin C in Rats Exposed to Sub-Chronic Low Doses of Cadmium. The Internet Journal of Toxicology. 2007 Volume 5 Number 1.

Abstract

In this study, the effects of vitamin C in cadmium-induced toxicity were investigated. Wister rats in different groups were exposed to cadmium (as CdSO4.8H2O), by sub-cutaneous injection, at doses of 1.0, 2.0 and 3.0 μg/kg body weight, with or without vitamin C supplementation, for four weeks. The serum alkaline phosphatase, of group III of the vitamin C untreated rats significantly (p<0.05) increased, all the groups of the vitamin C treated rats also had significantly (p<0.05) increased serum alkaline phosphatase. The bone protein level and serum calcium of the vitamin C untreated group of rats, significantly (p<0.05) decreased relative to its control. The bone calcium of the vitamin C treated rats significantly (p<0.05) decreased (group IIIc from 2896.30±344.64 mg Ca/dl to 1049±101.43 mg Ca/dl) while the bone phosphate of this same group of rats, significantly (p<0.05) increased. For some parameters evaluated, the effects of cadmium on the vitamin C treated rats were less pronounced, indicating that vitamin C may be protective against cadmium-induced toxicity.

 

Place of research: Department of Biochemistry, University of Benin, Benin City, Nigeria.

Research funding: The research was privately funded.

Introduction

Cadmium is a natural element in the earth's crust. It is usually found as a mineral combined with other elements such as oxygen (cadmium oxide), chlorine (cadmium chloride), or sulfur (cadmium sulfate, cadmium sulfide)( 1 ). The major intentional uses of cadmium are Nickel-Cd batteries, cadmium pigments, cadmium stabilisers, cadmium coatings, cadmium alloys and cadmium electronic compounds such as cadmium telluride (CdTe). The major classes of products where cadmium is present as an impurity are non-ferrous metals (zinc, lead and copper), iron and steel, fossil fuels (coal, oil, gas, peat and wood), cement, and phosphate fertilisers ( 2 ).

For non-smoking, non-occupationally exposed population, food, especially of vegetable origin, is the main source of cadmium exposure ( 3 ). Much of the cadmium which enters the body by ingestion comes from terrestrial foods i.e. from plants grown in soil or meat from animals which have ingested plants grown in soil. It is estimated that 98% of the ingested cadmium comes from terrestrial foods, while only 1% comes from aquatic foods such as fish and shellfish, and 1% arises from cadmium in drinking water ( 4 ).

An acute intake of cadmium causes testicular damage. Within a few hours of exposure, there is necrosis and degeneration of the testes with complete loss of spermatozoa. This is thought to be due to an effect on the blood supply to these organs, reducing the blood flow ( 5 ). If the cadmium is inhaled, then severe lung irritation and damage (often called ‘fume fever') occur. Pleuritic chest pain, dyspnoea, cyanosis, fever and tachycardia, and the pulmonary oedema, are some of the symptoms which occurs that may be life-threatening ( 6 ). Acute ingestion of cadmium produces severe gastrointestinal irritation, which is manifested as severe nausea and vomiting, abdominal cramps and diarrhoea. A lethal dose of cadmium for ingestion is estimated to be between 350 and 8900 milligrams ( 6 ). The chronic effects of cadmium are dose-dependent and also depend on the route by which the metal enters the body. Chronic inhalation causes emphysema and obstructive airways disease, and these occur before kidney damage is seen ( 7,6,5 ). Long term ingestion causes kidney damage, which is first seen as proteinuria and ß2microglobulinuria ( 6,8 ). In prolonged cadmium exposure, disorders of calcium metabolism occur, causing osteomalacia ( 6,8 ). This leads to painful fractures, hence the name given to the chronic exposure disease in Japan: Itai-itai disease (literally “ouch!-ouch!” disease) ( 6,8 ). Cadmium is also known to be carcinogenic, and in studies has been linked with cancers in the lungs and prostate ( 6,5,8 ).

Rivers containing excess cadmium can contaminate surrounding land, either through irrigation for agricultural purposes, dumping of dredged sediments or flooding. It has also been demonstrated that rivers can transport cadmium for considerable distances, up to 50 km, from the source ( 9 ). Nonetheless, studies of cadmium contamination in major river systems over the past twenty to thirty years have conclusively demonstrated that cadmium levels in these rivers have decreased significantly since the 1960s and 1970s ( 2,10,11,12 ).

Studies have shown that vitamin C supplementation has varied effects on induced toxicity ( 13 ). Ascorbic acid has been found to interact with several elements in such a way as to render them less available for animals ( 14 ). Grosicki ( 15 ) reported a decrease in the carcass cadmium burden and the cadmium contents in the liver, kidney, testicles and muscles of cadmium exposed rats (1.0-1.2mgCd/kgb.w) given water supplemented vitamin C (1.5mg/L) for 28days.

Apart from accidental and occupational exposure to cadmium, the general population is facing an increasing risk of cadmium exposure, a comprehensive and continuous monitoring of Warri River (Nigeria) between 1986 and 1991, showed that the average level of cadmium was 0.3mg/litre ( 16 ); this far exceeds the minimum allowable level of cadmium in drinking water (0.005mg/litre) ( 17 ). This study was designed to evaluate the protective effects of vitamin C in rats exposed to low doses of Cd, i.e. doses that are frequently encountered in the natural environment, as a means of ameliorating its toxic effects.

Materials and Methods

Chemicals and Reagents

Hydrated Cadmium Sulphate (CdSO4.8H2O) and other analytical grade chemicals used for this study were produced by E. Merch Darmstadt, Germany and BDH Chemical Limited, Poole, England. Pharmaceutical grade vitamin C tablets were obtained from Emzor Pharmaceuticals, Lagos, Nigeria. Alkaline Phosphatase and Calcium kits were products of Quimica Clinica Applicada SA (QCA), Spain, purchased from Equator Medics, Benin City, Nigeria.

Experimental Animals and Management

Forty-eight post weaning healthy albino rats (Rattus novergicus) of average weight 84.20g were obtained from the Animal Unit of Lagos University Teaching Hospital (LUTH), Nigeria, treatment of the animals was in accordance with the Principles of Laboratory Animal Care (NIH Publication 85-93, revised1985). They were divided into eight (8) groups of six (6) rats each. All the rats were maintained on commercial feeds, product of Bendel Feeds and Flour Mill, BFFM, Ewu, Nigeria. A set of four groups (I, II, III, and IV) corresponding to control, 1.0, 2.0 and 3.0µgCd/kg body weight were given water, while another set of four groups (Ic, IIc, IIIc and IVc) corresponding to control, 1.0, 2.0 and 3.0µgCd/kg body weight were given 5% vitamin C solution in place of water.

Once a day, for five days a week, the rats were given 0.25ml of the appropriate Cadmium solution or distilled water per 100g body weight by subcutaneous injection. Each rat was weighed weekly.

At the end of the fourth week, the rats were anaesthetized in a chloroform saturated chamber and while under the influence of the anaesthesia, the kidneys and femur bones were collected. The tissues were washed in ice cold physiological saline and then homogenized in ice cold physiological saline (1:4 wt/v of saline). The supernatant of the centrifuged homogenates were then separated, appropriately labeled and stored frozen until required. Blood was collected by heart puncture, allowed to clot on ice and then centrifuged at 5,000rpm for 5minutes, the sera was kept frozen until required.

One of the femur bones from each rat was ashed at 600 o C for 12hours in a Gallenkamp muffle furnace; model FR614, Gallenkamp &Co., England. The ashen bones (dissolved in 2M HCl) were used for the determination of bone calcium and inorganic phosphate.

Biochemical Analysis

Alkaline phosphatase (ALP) activity was measured spectrophotometrically at 550nm, in the serum, kidney and bones, using QCA alkaline phosphatase kits. The method measures spectrophotometrically, the intensity of the pink colour of phenolphthalein which is obtained by the hydrolysis of a colourless substrate phenolphthalein monophosphate by ALP ( 18 ).

Protein levels were measured spectrophotometrically at 540nm, in the serum, kidney and bone, using the Biuret method ( 19 ).

Serum and bone calcium were measured spectrophotometrically at 565nm, using QCA calcium kits. At alkaline pH, calcium forms a coloured complex with O-cresolpthalein, 8-hydroxyquinolein is added to the reagent as a chelating agent of magnesium ions which can interfere with the reaction ( 20 ).

Serum and bone inorganic phosphate were measured spectrophotometrically at 625nm, according to the method described by Plummer ( 21 ). In this method, ammonium molybdate-H2SO4 reagent reacts with inorganic phosphate to form complexes which is reduced to give a blue colour that can be read spectrophotometrically by adding 0.2% ascorbic acid.

Statistics: Values are expressed as means of 5 or 6 determinations ± SEM. The results obtained for the vitamin C treated and untreated groups were analyzed separately (within the column) by the Independent Samples T-test, each group was compared to its respective control on SPSS 11.0, SPSS Inc., Chicago, Illinois, USA.. A p<0.05 was considered statistically significant.

Results and Discussion

This study was designed to investigate the effects of vitamin C in rats exposed to sub-chronic (4 weeks) low doses of sub-cutaneously injected cadmium, with particular reference to kidney and bone toxicities. The overall toxic effects of continuous exposure to Cd were assessed by monitoring rat body weight gain and organ-body weight ratio.

Figure 1
Table 1: Body Weight of rats administered doses of cadmium

Table 1 shows a general steady increase in body weight gain in the vitamin C untreated and vitamin C treated groups of rats, however, while the final body weight of all tests groups of the vitamin C untreated rats decreased compared to control, only Group IIc of the vitamin C treated groups showed a statistically significant (p<0.05) decrease in final body weight compared to control, group IVc actually recorded a significantly (p<0.05) higher body weight compared to control. Asagba et al, ( 22 ) reported that rats given 3 mg Cd/ kg body weight ( as CdCl2) for 4 weeks, had statistically (p<0.05) lower final body weight compared to control. Ribas et al, ( 23 ) also reported that the pups of female rats supplied with drinking water containing 300 mg/l of CdCl2 during lactation, showed significantly lower (p<0.01) body weight than control pups. Grosicki and Kowalski ( 24 ), reported that rats exposed for 4 weeks to CdCl2 (labeled with cadmium-109) at 10 mg/ kg diet, showed a steady increase in average body weight gain throughout the experiment, however the final body weight of the rats exposed to Cd was markedly lower in comparison to the control rats. This observation totally correlates with the results obtained for the vitamin C untreated rats in this study.

Figure 2
Table 2: Organ- Body Weight Ratio of rats administered doses of cadmium.

Table 2 shows the general decreases observed in the bone- and kidney-body weight ratios for both set of rats, however, group IIc bone-body weight ratio was statistically similar to control, the kidney-body weight ratio of this same group was significantly (p<0.05) higher than control. Since chemical toxicity can be assessed by changes in the body weight and organ-body weight ratio ( 25 ), the significant alterations of these parameters in the Cd-treated rats, especially the vitamin C untreated rats implies Cd toxicity. The fact that only group IIc of the vitamin C treated rats showed a significant (p<0.05) decrease in body weight, while all the vitamin C untreated rats had significantly (p<0.05) decreased body weights, implies that vitamin C had a protective effect against the Cd-induced body weight reduction.

Since the kidney and bone are implicated in non-acute cadmium exposure, the serum, kidney and bone ALP were determined in this study.

Figure 3
Table 3: Serum, kidney and bone alkaline phosphatase of rats administered doses of cadmium.

The bile canaliculli of the liver, osteoblasts in the bone, proximal tubules in the kidney and mucosal cells of the small intestine, are rich sources of alkaline phosphatase ( 26 ). Damage to any of these organs or tissues would lead to elevated activity of its isoform of ALP in the serum ( 27,28 ). Table 3 shows significant (p<0.05) decreases observed in tissue ALP of almost all the groups of the vitamin C untreated and vitamin treated rats. Axelsson and Piscator ( 29 ), reported a reduction in the ALP activity of renal cortex in rabbits given 0.5mgCd/kg body weight. Saillenfait et al, ( 30 ) also reported that pups from pregnant rats intraperitoneally injected with CdCl2 at 2.5 mg/kg body weight for up to 14 days of gestation, exhibited significant decreases in renal ALP activity.

The significantly high serum ALP (Table 3) observed in this study could be as a result of the leakage of this enzyme from damaged tissues, rich in ALP, into the blood stream, this is particularly evident in the vitamin C treated groups where both bone and kidney ALP were significantly (p<0.05) decreased while the serum enzyme significantly (p<0.05) increased. Itokawa et al ( 31 ) observed an increase in the activity of serum ALP coincident with changes in the skeleton after 120days of oral exposure to 50ppm cadmium. Akesson et al, ( 32 ), using a population based women's health survey in Southern Sweden to investigate the association between low-level cadmium exposure and osteoporosis, reported that urinary cadmium displayed a near-significant (p<0.06) association with serum bone-alkaline phosphatase (bALP). Since the kidney and bone, are established target organs of cadmium toxicity ( 33,34 ); in addition to the decreased tissue ALP observed in this study, it is plausible to conclude that the increase in serum ALP is a reflection of the decreased bone and kidney ALP.

Serum total protein level is a rough measure of protein status but reflects major functional changes in kidney and liver functions ( 35 ).

Figure 4
Table 4: Serum, kidney and bone protein levels of rats administered doses of cadmium.

Table 4 shows the serum, kidney and bone protein levels. Low doses of cadmium administration for 4 weeks appears to have a general lowering effect on the bone, kidney and serum protein levels of the vitamin C treated groups. Also, the significant reduction in the bone protein level of group IV of the Vitamin C untreated rats, show that cadmium interferes with bone protein levels. The reductions observed in the bone, kidney, and serum protein levels of all test groups of the vitamin C treated rats are puzzling, however, since statistical analysis show that vitamin C alone significantly (p<0.05) increased the bone, kidney and serum protein levels of group Ic (Table 7), the reductions observed can be attributed to cadmium-induced toxicity. Proteinuria due to kidney impairment in cadmium toxicity may be the cause of protein loss in the test groups since inhibitory role of cadmium in protein synthesis has not been established.

The reduction in serum calcium in the vitamin C untreated groups is a reflection of the effect of cadmium on calcium metabolism (Table5)

Figure 5
Table 5: Serum and bone calcium levels of rats administered doses of cadmium.

The decreased Ca 2+ absorption and negative Ca balance in cadmium exposed rats could result from the inhibitory effect of cadmium on the activation of vitamin D in renal cortical cells ( 36 ). Nogawa et al ( 37 ) reported that serum 1, 25-dihydroxylcholecalciferol levels were lower in Itai-Itai disease patients and cadmium exposed subjects with renal damage. A reduction in serum calcium level (hypocalcaemia) stimulates the release of calcium from bone, this correlates well with the reduced bone calcium observed in the test groups of the vitamin C untreated and vitamin C treated rats. Itokawa et al ( 31 ) reported that simultaneous administration of cadmium with a low-protein, low-calcium diet led to a decrease in calcium and zinc content of the bone.

Available data show that cadmium can affect calcium, phosphorus and bone metabolism ( 11 ). Reductions in serum 1, 25-dihydroxycholecalciferol in cadmium-exposed subjects, are closely related to serum concentrations of parathyroid hormone (PTH), β2-microglobulin and the percentage tubular reabsorption of phosphate ( 37 ), suggesting that cadmium-induced bone effects may also be due to disturbances in vitamin D and PTH metabolism ( 38 ). Phosphorus is important for the modulation of calcium mobilization from the bone and the regulation of plasma calcium ( 39 ). Increase in serum calcium is associated with decrease in serum phosphorus and increased urinary phosphorus excretion and vice versa ( 39 ).

Figure 6
Table 6: Serum and bone phosphate levels of rats administered doses of cadmium.

The results obtained for serum calcium and phosphate in this study (Tables 5 and 6) does not sufficiently reflect the reciprocal relationship between calcium and phosphorus, however, group IVc, of the vitamin C treated rats, shows an increased calcium level while its phosphate level is decreased. The results for bone calcium and phosphate levels of the vitamin C treated rats, correlates better with the reciprocal relationship between calcium and phosphorus.

The statistical analysis of groups I and Ic, using Independent Samples T-test on SPSS 11.0, showed that vitamin C alone positively influenced most of the parameters evaluated (Table 7).

Figure 7
Table 7: Effect of Vitamin C on all Parameters Evaluated

For some of the parameters evaluated, recognizable differences were observed between the vitamin C untreated and the vitamin C treated groups of rats, these include:

The final body weights of groups IIIc and IVc of the vitamin C treated rats did not decrease relative to control, while all the groups of the vitamin C untreated rats decrease compared to their control

The bone protein concentration of group IV of the vitamin C untreated groups of rats showed a statistically significant (p<0.05) decrease compared to its control, while there was no significant difference in group IVc of the vitamin C treated groups, compared to its control.

While a significant (p<0.05) decrease in serum calcium was observed in all the vitamin C untreated groups, group IVc of the vitamin C treated groups, showed a significant increase compared to its control

Cadmium may also exert its toxicity via oxidative damage. Valko et al ( 40 ) reported that the primary route for cadmium toxicity is depletion of glutathione and binding to sulfhydryl groups of protein. It is therefore not surprising that vitamin C, an antioxidant, would play a protective role against cadmium toxicity.

Conclusion

The findings from this study have shown that subcutaneous administration of low doses of cadmium to rats either with or without vitamin C supplementation caused an increase in serum ALP and bone phosphate. It also caused a decrease in bone protein concentration, serum calcium and bone calcium, indicating that under the conditions of this study, the bone is the major target of cadmium toxicity. The result also shows that vitamin C may play a protective role against cadmium toxicity, implying that vitamin C can be used to ameliorate the toxic effect of low doses of cadmium.

Acknowledgments

I am grateful for the scientific advice of Profs. I. O. Onoagbe, P. O. Uadia, and Dr P. N. Okolie of the Department of Biochemistry, University of Benin, Benin City, Nigeria. I am also grateful for the support of the technical staff. I am especially grateful to my research partner, Mr Marshal Ishuekevbo, rest in peace.

Correspondence to

Name: Omonkhua Akhere A. Address: Department of Biochemistry, Adekunle Ajasin University, Akungba- Akoko, Ondo State, Nigeria. E-mail: aaomonkhua@yahoo.com

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for cadmium. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service. 1999.
2. Cook ME, Morrow H. Anthropogenic sources of cadmium in Canada. National Workshop on Cadmium Transport into Plants, Canadian Network of Toxicology Centres, Ottawa, Ontario, Canada. 1995; June, 20-21.
3. Kierstin PG. Lactational transfer of cadmium in rodents - CNS: Effects in the offspring. Acta Universitatis Agriculturae Sueciae. Veterinaria Vol. 150. Doctoral Thesis. 2003; Pp 10-11.
4. Van Assche FJ. A stepwise model to quantify the relative contribution of different environmental sources to human cadmium exposure, Paper presented at NiCad '98, Prague, Czech Republic, 1998; September 21-22.
5. Timbrell JA. Cadmium. In: Introduction to Toxicology. 2nd edition. Taylor and Francis, London. 1995; Pp 76-77.
6. Fauci AS, Braunwald K, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL. (eds). Heavy metal poisoning. in: Harrison's Principles of Internal Medicine. 14th ed. McGraw-Hill, New York. 1998; Pp2564-2569.
7. Baldwin DR, Marshall WJ.. Heavy metal poisoning and its laboratory investigation (Review Article). Ann. Clin. Biochem. 1999; 36: 267-300.
8. Williams F, Robertson R, Roworth M. Scottish Centre for Infection and Environmental Health. Detailed Profile of 25 Major Organic and Inorganic Substances. 1st ed. Glasgow: SCEIH. 1999.
9. WHO. Environmental Health Criteria 134: Cadmium-Environmental Aspects. Geneva, World Health Organization. 1992.
10. Elgersma F, Anderberg BS, Stigliani WM. Emission factors for aqueous industrial cadmium emissions in the Rhine river basin; A historical reconstruction for the period 1970-1988, Edited Proceedings Seventh International Cadmium Conference - New Orleans, Cadmium Association, London, Cadmium Council, Reston VA, International Lead Zinc Research. 1992.
11. Mukunoki J, Fujimoto K. Collection and recycling of used Ni-Cd batteries in Japan, sources of cadmium in the environment, Inter-Organisation Programme for the Sound Management of Chemicals (IOMC), Organisation for Economic Co-operation and Development (OECD), Paris, 1996.
12. Van Assche FJ, Ciarletta P. Cadmium in the environment: levels, trends and critical pathways. Edited Proceedings Seventh International Cadmium Conference - New Orleans, Cadmium Association, London, Cadmium Council, Reston VA, International Lead Zinc Research Organisation, Research Triangle Park NC. 1992.
13. Netke SP, Roomi MW, Tsao C, Niedzwiecki A. Ascorbic acid protects guinea pigs from acute aflatoxin toxicity. Toxicol. Appl. Pharm. 1997; 143:429-435.
14. Hill CH. Interactions of vitamin C with lead and mercury. Ann. NY. Acad. Sci. 1980; 355: 262-266.
15. Grosicki A. Influence of vitamin C on cadmium absorption and distribution in rats. J. Trace Elem. Med. Biol. 2004; 18(2): 183-187.
16. Egborge ABM. Water pollution in Nigeria. Biodiversity and chemistry of Warri river. Ben Miller Books Nig. Nigeria. 1994; Pp 32.
17. WHO. Guidelines for Drinking-water Quality: Health Criteria and Other Supporting information. World Health Organization, Geneva. 1984; Vol. 2 Pp. 84-90.
18. Babson AL, Greeley SJ, Coleman CM, Phillips GE. Phenolphthalein monophosphate as a substrate for serum alkaline phosphatase. Clin. Chem. 1966; 12: 482-490.
19. Gornall AG, Bardawill JC, David MM. Determination of serum proteins by means of Biuret reaction. J. Biol. Chem. 1949; 177: 751-760.
20. Baginski ES, Marie SS, Clark WL, Zak B. Direct microdetermination of serum calcium. Clin. Chim Acta. 1973; 46:49-54.
21. Plummer DT. An Introduction to practical biochemistry. McGraw Hill Ltd. Mardenhead Berkshire, England. 1978; Pp. 109-185.
22. Asagba SO, Adiakpoh MA, Kadiri H, Obi FO. Influence of aqueous extract of Hibiscus sabdariffa L. petals on cadmium toxicity in rats. Biol. Trace Elem. Res. 2006; 115: 47-57.
23. Ribas JP, Lopes RA, Sala MA, Ribas LMR, de Mattos MC, Semprini M, Watanabe I, Regalo SCH. Effect of cadmium on rat maxillary molar junctional epithelium during lactation. Int. J. Morphol. 2004; 22(4): 257-262.
24. Grosicki A, Kowalski B. Whole body and organ retention of cadmium after repeated administration to rats. Bull. Vet. Inst. Pullawy. 2002; 46: 143-147.
25. Timbrell JA. Principles of Biochemical Toxicology. 2nd Edition Taylor & Francis, London, Washington DC. 1991; Pp. 369-370.
26. Verley H. Practical Clinical Biochemistry, 4th edition, Heinemann Medical Books Ltd and New York Interscience Books, Inc, New York. 1967; Pp 891 - 921
27. Ngaha EO, Akanji MA, Madusuolumo MA. Studies on correlation between chloroquine - induced tissue damage and serum enzyme changes in the rat. Experientia. 1989; 45: 143 - 146.
28. Lin JK, Wang CJ. Protection of crocin dyes in the acute hepatic damage induced by aflatoxin b1 and dimethylnitrosamine in rats. Carcinogenesis. 1986; 595 - 599.
29. Axelsson B, Piscator M, Renal damage after prolonged exposure to cadmium: An experimental study. Arch. Environ. Health. 1966; 12: 360-373.
30. Saillenfait AM, Payan JP, Ban M, de Ceaurriz J. Indirect and lactation-associated changes in renal alkaline phosphatase of newborn rats prenatally exposed to cadmium chloride. J. Appl. Toxicology. 2006; 12(3)205-210.
31. Itokawa Y, Nishino K, Takashima M, Nakata T, Katto H, Okamoto E, Daijo K, Kawamura J. Renal and skeletal lesions in experimental cadmium poisoning of rats. Histology and renal function. Environ. Res. 1978; 15: 206-217.
32. Akesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, Skeefving S, Vahter M. Cadmium-induced effects on bone in a population-based study of women. Environ. Health Perspect. 2006; 114(6):830-834.
33. Kido T, Kobayashi E, Hayano M, Nogawa K, Tsuritani I, Nishijo M, Tabata M, Nakagawa H, Nuyts GD, Debroe ME. Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium. Toxicol. Lett. 1995; 80 (1-3): 49 - 54.
34. Ahn DW, Park YS. Transport of inorganic phosphate in renal cortical brush-border membrane vesicles of cadmium intoxicated rats. Toxicol. Appl. Pharmacol. 1995; 133 (2): 239 - 243.
35. Pachathundikandi SK, Verghese ET. Blood Zinc Protoporphyrin, Serum total protein, and total cholesterol levels in automobile workshop workers in relation to lead toxicity: Our experience. Indian J. Clin. Biochem. 2006; 21(2)114-117.
36. Feldman SL, Cousins RG. Influence of cadmium on the metabolism of 25-hydroxycholecalciferol in chicks. Nutr. Rep. Int. 1973; 8: 251-259.
37. Nogawa K, Tsuritani I, Kido T, Honda R, Tamada Y, Ishizaki MC. Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: Decreased serum 1 & 1, 25-dihydroxy vitamin D level. Int. Arch. Occup. Environ. Health. 1987; 59: 21-30.
38. Kjellstrom T. Mechanism and epidemiology of bone effects of cadmium. IARC Sci. Publ. 1992; 118; 301-310.
39. Felsenfeld AJ, Rodriguez M. Phosphorus, regulation of plasma calcium, and secondary hyperthyroidism: A hypothesis to integrate a historical and modern perspective. Review Article. J. Am. Soc. Nephrol. 1999; 10:878-890.
40. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative Stress. Curr. Med. Chem. 2005; 12(10): 1161-1208.

Author Information

Akhere A. Omonkhua, M.Sc Biochemistry
Adekunle Ajasin University

Fredrick O. Obi, PhD Biochemistry
University of Benin

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