Minerals and Trace Elements
Effect of Ethanol on Cadmium Uptake and Metabolism of Zinc and Copper in Rats Exposed to Cadmium1 Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India known causes of abnormal human development (3). Metabolism and toxicity of heavy metals may be influenced by ethanol or its metabolites (4), which are capable of producing a secondary nutritional defi ciency by interfering with the metabolism of essential nutrients, including trace metals, through effects on absorption, tissue redistribution or excretion. Because ethanol diffuses readily across all biological mem branes except skin, it can be absorbed from all parts of the gastrointestinal tract, lungs, urinary bladder and pleural cavities. After absorption, ethanol diffuses very rapidly across capillary and other membranes so that it ultimately distributes uniformly throughout the whole body (5). Ethanol has been found to enhance the absorption of lead in the body, and alcoholics have been reported to be more susceptible to lead intoxication than nonalcoholics (6). It has also been observed that animal» co-exposed to ethanol and lead are more vulnerable to the systemic toxicity of lead, including neurotoxic effects (5). Cadmium toxicity leads to depressed intestinal ab sorption of zinc and copper because of cadmiuminduced enteropathy (7). In liver and kidney both zinc and copper concentration decrease rapidly, resulting in copper-deficiency anemia (8). Although metal shifts are known to be early indicators of response to toxic agents and of human diseases such as schizophrenia, epilepsy and Wilson's disease (9), the interaction of toxic metals with essential trace metals present as functional groups of cellular components is still an unexplored field in relation to cadmium and alcohol toxicity. Because alcoholism is a serious problem in almost all industrialized nations as well as in developing countries (3), it was considered of in terest to investigate the influence of ethanol and
ABSTRACT Effects of chronic administration of cadmium and ethanol, alone as well as in combination, on the uptake of cadmium and its interaction with other essential trace elements in various tissues of adult rats were investigated. Cadmium given in combination with ethanol led to a pronounced increase in cadmium ab sorption and accumulation in all the tissues studied rel ative to both non-exposed controls and rats treated with cadmium alone. Both cadmium and ethanol exhibited specific effects on copper and zinc levels of the tissues. These effects often were significantly altered when the animals were co-exposed to cadmium and ethanol. The results suggested that although both cadmium and ethanol individually pose a hazard to essential trace metal homeostasis of various organs, co-exposure can pose a major threat since animals exposed to ethanol absorb much more cadmium than their unexposed coun terparts. J. Nutr. 121:87-91, 1991. INDEXING KEY WORDS:
•cadmium •ethanol •copper •zinc •rats
Heavy metals constitute a major portion of envir onmental pollutants. Among a wide range of heavy metals emitted in air which are injurious to health, cadmium has been placed at the top of the priority list by the World Health Organization (1). The problem of cadmium toxicity has become especially important as cadmium concentrations in the envir onment have begun to rise tremendously because of a variety of human activities such as mining, the metal lurgical industry, coal combustion and the use of cadmium-containing fertilizers. The main routes of cadmium absorption are via the respiratory and gas trointestinal tracts. The absorption rate is 10-40% through respiratory organs and 4.7-7% from the gas trointestinal tract (2). Conversely, excessive consumption of ethanol is currently recognized as among the most prevalent
'Financial assistance provided by the Indian Council of Medical Research, New Delhi, is duly acknowledged.
0022^166/91 $3.00 ©1991 American Institute of Nutrition. Received 24 May 1989. Accepted 23 July 1990. 87
Downloaded from https://academic.oup.com/jn/article-abstract/121/1/87/4738658 by Tulane University user on 11 February 2019
GEETA SHARMA, RAJAT SANDH1R, RAVINDRA NATM AND KIRANDIP GILL
SHARMA ET AL.
88
cadmium co-exposure on Cd accumulation and on the homeostasis of copper and zinc.
METHODS
RESULTS Tables 1-3 show the concentrations of cadmium, zinc and copper in various tissues of control and
TABLE 1 Effect of intragastric cadmium (Cd), ethanol (Et) and their combination oa cadmium concentration in various tissues of rats' 1 (control)0.13 TissueLiverKidneyIntestineSpleenHeartLungsCroup
2 l+Cd)MS14.97 (+Et)Cd/g
4
6 (+Cd+Et)27.54
wet wt0.30 3.15*8.80 ± 0.07*0.44 ± 4.13*"15.45 ± 0.010.12 ± 0.82*8.69 ± 0.22"50.99 ± 2.11*-*20.71 ± 0.010.23 ± 0.88*5.75 ± 0.07*1.36 ± 2.69*'*8.95 ± 0.050.53 ± 1.54*2.31 ± 0.49NS0.93 ± 0.34*-»2.94 ± ±0.110.28 0.21*0.72 ± 0.17™0.22 ± 0.27*-*1.89 ± 0.070.12 ± ±0.22*Group ±0.051*Group ±0.55*'* ±0.01Croup 'Each value is the mean ± so of 5-7 animals. Statistical analysis was conducted using preplanned orthogonal contrasts following ANOVA. F values less than that of 5% level were considered significant. *•*: Values are significantly different as compared to group 1 and group 2, respectively; NS - nonsignificant.
Downloaded from https://academic.oup.com/jn/article-abstract/121/1/87/4738658 by Tulane University user on 11 February 2019
Animals. Male albino rats (Wistar strain) weighing 100-150 g were obtained from the Institute animal house. The animals were housed in polypropylene cages with stainless steel lids and fed a pelleted nonpurified rat diet (Hindustan Lever, Bombay, India) and water ad libitum. Experimental design. Animal«were divided into the following seven groups of five to seven animals each and were treated for 30 d. Group 1. Animals were fed the nonpurified diet and water ad libitum. This group served as the control group. Group 2. Each day for 30 d, animals were intragastrically given 10 mg cadmium (as CdCl2)/kg body weight and were fed the nonpurified diet and water ad libitum. Group 3, Animals were fed the nonpurified diet in the same amount consumed by group 2. This group thus served as the cadmium pair-fed group. Group 4. Animals were given 7 mL of 10% ethanol (v/v) intragastrically. The daily intake of ethanol thus amounted to 5.56 g/kg body weight. Nonpurified diet was given ad libitum. Group 5. To make an ethanol pair-fed group, animals in this group were given isoenergetically sub stituted sucrose in place of ethanol and were fed nonpurified diet in the same amount as consumed by group 4. Group 6. Cadmium was administered as in group 2 along with ethanol as in group 4. Group 7. Cadmium (10 mg/kg body weight) as CdCl2 and isoenergetically substituted sucrose were given along with diet equal in amount to that taken
by group 6. This group thus served as a cadmium + ethanol pair-fed group. After 30 d of treatment, animals were fasted over night, anesthetized and killed by decapitation. Various organs, including liver, kidney, intestine, lungs, spleen and heart, were removed and washed thoroughly in 9 g/L NaCl. Tissues were frozen at -20"C until further use. (
Effect of Ethanol on Cadmium Uptake and Metabolism of Zinc and Copper in Rats Exposed to Cadmium1 Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India known causes of abnormal human development (3). Metabolism and toxicity of heavy metals may be influenced by ethanol or its metabolites (4), which are capable of producing a secondary nutritional defi ciency by interfering with the metabolism of essential nutrients, including trace metals, through effects on absorption, tissue redistribution or excretion. Because ethanol diffuses readily across all biological mem branes except skin, it can be absorbed from all parts of the gastrointestinal tract, lungs, urinary bladder and pleural cavities. After absorption, ethanol diffuses very rapidly across capillary and other membranes so that it ultimately distributes uniformly throughout the whole body (5). Ethanol has been found to enhance the absorption of lead in the body, and alcoholics have been reported to be more susceptible to lead intoxication than nonalcoholics (6). It has also been observed that animal» co-exposed to ethanol and lead are more vulnerable to the systemic toxicity of lead, including neurotoxic effects (5). Cadmium toxicity leads to depressed intestinal ab sorption of zinc and copper because of cadmiuminduced enteropathy (7). In liver and kidney both zinc and copper concentration decrease rapidly, resulting in copper-deficiency anemia (8). Although metal shifts are known to be early indicators of response to toxic agents and of human diseases such as schizophrenia, epilepsy and Wilson's disease (9), the interaction of toxic metals with essential trace metals present as functional groups of cellular components is still an unexplored field in relation to cadmium and alcohol toxicity. Because alcoholism is a serious problem in almost all industrialized nations as well as in developing countries (3), it was considered of in terest to investigate the influence of ethanol and
ABSTRACT Effects of chronic administration of cadmium and ethanol, alone as well as in combination, on the uptake of cadmium and its interaction with other essential trace elements in various tissues of adult rats were investigated. Cadmium given in combination with ethanol led to a pronounced increase in cadmium ab sorption and accumulation in all the tissues studied rel ative to both non-exposed controls and rats treated with cadmium alone. Both cadmium and ethanol exhibited specific effects on copper and zinc levels of the tissues. These effects often were significantly altered when the animals were co-exposed to cadmium and ethanol. The results suggested that although both cadmium and ethanol individually pose a hazard to essential trace metal homeostasis of various organs, co-exposure can pose a major threat since animals exposed to ethanol absorb much more cadmium than their unexposed coun terparts. J. Nutr. 121:87-91, 1991. INDEXING KEY WORDS:
•cadmium •ethanol •copper •zinc •rats
Heavy metals constitute a major portion of envir onmental pollutants. Among a wide range of heavy metals emitted in air which are injurious to health, cadmium has been placed at the top of the priority list by the World Health Organization (1). The problem of cadmium toxicity has become especially important as cadmium concentrations in the envir onment have begun to rise tremendously because of a variety of human activities such as mining, the metal lurgical industry, coal combustion and the use of cadmium-containing fertilizers. The main routes of cadmium absorption are via the respiratory and gas trointestinal tracts. The absorption rate is 10-40% through respiratory organs and 4.7-7% from the gas trointestinal tract (2). Conversely, excessive consumption of ethanol is currently recognized as among the most prevalent
'Financial assistance provided by the Indian Council of Medical Research, New Delhi, is duly acknowledged.
0022^166/91 $3.00 ©1991 American Institute of Nutrition. Received 24 May 1989. Accepted 23 July 1990. 87
Downloaded from https://academic.oup.com/jn/article-abstract/121/1/87/4738658 by Tulane University user on 11 February 2019
GEETA SHARMA, RAJAT SANDH1R, RAVINDRA NATM AND KIRANDIP GILL
SHARMA ET AL.
88
cadmium co-exposure on Cd accumulation and on the homeostasis of copper and zinc.
METHODS
RESULTS Tables 1-3 show the concentrations of cadmium, zinc and copper in various tissues of control and
TABLE 1 Effect of intragastric cadmium (Cd), ethanol (Et) and their combination oa cadmium concentration in various tissues of rats' 1 (control)0.13 TissueLiverKidneyIntestineSpleenHeartLungsCroup
2 l+Cd)MS14.97 (+Et)Cd/g
4
6 (+Cd+Et)27.54
wet wt0.30 3.15*8.80 ± 0.07*0.44 ± 4.13*"15.45 ± 0.010.12 ± 0.82*8.69 ± 0.22"50.99 ± 2.11*-*20.71 ± 0.010.23 ± 0.88*5.75 ± 0.07*1.36 ± 2.69*'*8.95 ± 0.050.53 ± 1.54*2.31 ± 0.49NS0.93 ± 0.34*-»2.94 ± ±0.110.28 0.21*0.72 ± 0.17™0.22 ± 0.27*-*1.89 ± 0.070.12 ± ±0.22*Group ±0.051*Group ±0.55*'* ±0.01Croup 'Each value is the mean ± so of 5-7 animals. Statistical analysis was conducted using preplanned orthogonal contrasts following ANOVA. F values less than that of 5% level were considered significant. *•*: Values are significantly different as compared to group 1 and group 2, respectively; NS - nonsignificant.
Downloaded from https://academic.oup.com/jn/article-abstract/121/1/87/4738658 by Tulane University user on 11 February 2019
Animals. Male albino rats (Wistar strain) weighing 100-150 g were obtained from the Institute animal house. The animals were housed in polypropylene cages with stainless steel lids and fed a pelleted nonpurified rat diet (Hindustan Lever, Bombay, India) and water ad libitum. Experimental design. Animal«were divided into the following seven groups of five to seven animals each and were treated for 30 d. Group 1. Animals were fed the nonpurified diet and water ad libitum. This group served as the control group. Group 2. Each day for 30 d, animals were intragastrically given 10 mg cadmium (as CdCl2)/kg body weight and were fed the nonpurified diet and water ad libitum. Group 3, Animals were fed the nonpurified diet in the same amount consumed by group 2. This group thus served as the cadmium pair-fed group. Group 4. Animals were given 7 mL of 10% ethanol (v/v) intragastrically. The daily intake of ethanol thus amounted to 5.56 g/kg body weight. Nonpurified diet was given ad libitum. Group 5. To make an ethanol pair-fed group, animals in this group were given isoenergetically sub stituted sucrose in place of ethanol and were fed nonpurified diet in the same amount as consumed by group 4. Group 6. Cadmium was administered as in group 2 along with ethanol as in group 4. Group 7. Cadmium (10 mg/kg body weight) as CdCl2 and isoenergetically substituted sucrose were given along with diet equal in amount to that taken
by group 6. This group thus served as a cadmium + ethanol pair-fed group. After 30 d of treatment, animals were fasted over night, anesthetized and killed by decapitation. Various organs, including liver, kidney, intestine, lungs, spleen and heart, were removed and washed thoroughly in 9 g/L NaCl. Tissues were frozen at -20"C until further use. (
