Toxic effects vitamins

Some vitamins (A, D, E, and K) have very nonpolar molecular structures and therefore dissolve only in nonpolar solvents. In the body, the nonpolar solvents are the lipids we have classified as fats, so these vitamins are called fat-soluble. The fat-soluble vitamins have diverse functions in the body, and they act somewhat like hormones (Table 12.3). Care must be taken to avoid overdoses of the fat-soluble vitamins. Toxic effects are known to occur, especially with vitamin A, when excess amounts of these vitanfins accumulate in body tissue. Excesses of water-soluble vitamins are excreted readily through the kidneys and are not normally a problem. 

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Some hydroxy metabolites of coplanar PCBs, such as 4-OH and 3,3 4,5 -tet-rachlorobiphenyl, act as antagonists of thyroxin (Chapter 6, Section 6.2.4). They have high affinity for the thyroxin-binding site on transthyretin (TTR) in plasma. Toxic effects include vitamin A deficiency. Biomarker assays for this toxic mechanism include percentage of thyroxin-binding sites to which rodenticide is bound, plasma levels of thyroxin, and plasma levels of vitamin A. 

Perumal, A.S., Gopal, V.B., Tordzro, W.K., Cooper, T.B. and Cadet, J.L. (1992). Vitamin E attenuates the toxic effects of 6-hydrooxydopamine on free radical scavenging systems in rat brain. Brain Res. Bull. 29, 699-701. 

It is important that children have proper nutrition and eat a balanced diet of foods that supply adequate amounts of vitamins and minerals, especially calcium and iron. Good nutrition lowers the amount of swallowed lead that passes to the bloodstream and also may lower some of the toxic effects of lead. 

Both vitamin E and vitamin C are able to react with peroxynitrite and suppress its toxic effects in biological systems. For example, it has been shown [83] that peroxynitrite efficiently oxidized both mitochondrial and synaptosomal a-tocopherol. Ascorbate protected against peroxynitrite-induced oxidation reactions by the interaction with free radicals formed in these reactions [84]. 

Yonemoto, J., H. Satoh, S. Himeno, and T. Suzuki. 1983. Toxic effects of sodium selenite on pregnant mice and modification of the effects by Vitamin E or reduced glutathione. Teratology 28 333-340. 

No information is available on the adverse health effects of hexachloroethane in humans. Animal studies revealed that hexachloroethane primarily causes liver and kidney toxicity. Effects on the nervous system and lungs have also been reported. The mechanism by which these effects are mediated is not well characterized. Reductive metabolism by cytochrome P-450 and production of a free radical intermediate have been suggested as factors in hexachloroethane-induced hepatotoxicity (Nastainczyk et al. 1982a Thompson et al. 1984 Town and Leibman 1984). Accordingly, one possible approach may be to reduce free radical injury. To that end, oral administration of N-acetylcysteine can be used as a means of reducing free radical injury. Also, oral administration of vitamin E and vitamin C may be of value since they are free radical scavengers. 

Selenium is readily available in a variety of foods including shrimp, meat, dairy products, and grains, with a recommended daily intake of 55 to 70 jug. It occurs in several forms with Se+6 being biologically most important. Selenium is readily absorbed by the intestine and is widely distributed throughout the tissues of the body, with the highest levels in the liver and kidney. It is active in a variety of cellular functions and interacts with vitamin E. Selenium appears to reduce the toxic effects of metals such as cadmium and mercury and to have anticarcinogenic activity. Selenium produces notable adverse effects both in deficiency and excess thus recommended daily intake for adults is approximately 70 Jg/day but should not exceed 200 pg/day. 

Itching associated with retention of bile acids is ameliorated by treatment with the bile acid binding resin cholestyramine. Fat soluble vitamin (A, D and K) deficiency may require administration of supplements. Direct toxic effects of alcohol associated with dietary deficiency may require soluble B vitamin administration. 

Toxic effects have been observed when large dosages of some vitamins are ingested. Generally the water-soluble vitamins are less toxic, since excess quantities are usually excreted in the urine. Excessive amounts of fat-soluble vitamins, however, are stored in the body, which makes toxic levels of these vitamins easier to obtain. 

The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort, and diarrhea), which occur in up to 20% of patients. They are dose-related, tend to occur at the onset of therapy, and are often transient. However, metformin may have to be discontinued in 3-5% of patients because of persistent diarrhea. Absorption of vitamin B12 appears to be reduced during long-term metformin therapy, and annual screening of serum vitamin B12 levels and red blood cell parameters has been encouraged by the manufacturer to determine the need for vitamin B12 injections. In the absence of hypoxia or renal or hepatic insufficiency, lactic acidosis is less common with metformin therapy than with phenformin therapy. 

Corticosteroids are extremely useful in elderly patients who cannot tolerate full doses of NSAIDs. However, they consistently cause a dose- and duration-related increase in osteoporosis, an especially hazardous toxic effect in the elderly. It is not certain whether this drug-induced effect can be reduced by increased calcium and vitamin D intake, but it would be prudent to consider these agents (and bisphosphonates if osteoporosis is already present) and to encourage frequent exercise in any patient taking corticosteroids. 

Prolonged administration of large doses of vitamin K can produoe hemolytic anemia and jaundice in the infant, due to toxic effects on the membrane of red blood cells. 

Populations that are unusually susceptible to toxic effects of silver exposure are those that have a dietary deficiency of vitamin E or selenium, or that may have a genetically based deficiency in the metabolism of these essential nutrients. Individuals with damaged livers may also be more susceptible to the effects of silver exposure. In addition, populations with high exposures to selenium may be more likely to develop argyria. Furthermore, some individuals may exhibit an allergic response to silver. 

The toxic effects associated with PCN exposures in humans and wildlife are, in general, characteristic of effects due to chlorinated hydrocarbons such as 2,3,7,8-TCDD. For instance, chloracne, vitamin A depletion, edema and liver damage have been observed in animals exposed to TCDD. The human toxicity and mechanistic relationship of PCNs to TCDD may be useful in understanding these classes of compounds. Particularly, acute and subacute exposures of humans and cattle to PCNs may provide important clues to the toxic effects at high levels for other dioxin-like compounds. 

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