Vitamin hepatotoxicity

ElSisi, A.E.D., Earnest, D.L. and Sipes, LG. (1993a). Vitamin-A potentiation of carbon tetrachloride hepatotoxicity -enhanced lipid peroxidation without enhanced biotransformation. Toxicol. Appl. Pharmacol. 119, 289-294. 

Prognosis is more favorable in the pyridoxine-respon-sive patients. Patients who respond to large doses of vitamin B6 (250-500 mg/day for several weeks) have the best prognosis. Efficacy of treatment usually is reflected in a reduction of blood homocystine and methionine to normal or near-normal levels. Since supplementation with pyridoxine can cause a deficiency of folic acid, the latter should be given (2-5 mg daily) at the same time. Any patient receiving pyridoxine should be monitored carefully for any signs of hepatotoxicity and for a peripheral neuropathy (see Ch. 36). 

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. 

Miscellaneous Hepatotoxicity stored in 0.01% thymol light sensitive Coronary steal maintains renal blood flow Hepatotoxic avoid in renal impairment Renal toxicity Oxidizes cobalt ion in vitamin B12... 

No specific antidote has been shown to be effective in treating 1,2-dibromoethane intoxication once absorption into the bloodstream has occurred (Ellenhorn and Barceloux 1988). Intravenous infusions of glucose may limit the hepatotoxicity of 1,2-dibromoethane (ERA 1989b). During the recovery phase, a diet rich in vitamin B and carbohydrates may limit liver damage (Dreisbach and Robertson 1987 Lawrence and Michaels 1984). Hemodialysis may be needed to regulate extracellular fluid and electrolyte balance and to remove metabolic waste products if renal failure occurs (ERA 1989b). 

The activity of vitamin A is related to vision process, tissue differentiation, growth, reproduction, and the immune system. A deficiency of this micronutrient mainly leads to visual problems, impaired immune function, and growth retardation in children. Hypervitaminosis could lead to hepatotoxicity, affect bone metabolism, disrupt lipid metabolism, and teratogenicity [417]. The isomerization of P-carotene, due to technological processes in foods, leads to a reduction of the vitamin A activity it is therefore important to analyze it. 

Haloalkanes. Certain haloalkanes and haloalkane-containing mixtures have been demonstrated to potentiate carbon tetrachloride hepatotoxicity. Pretreatment of rats with trichloroethylene (TCE) enhanced carbon tetrachloride-induced hepatotoxicity, and a mixture of nontoxic doses of TCE and carbon tetrachloride elicited moderate to severe liver injury (Pessayre et al. 1982). The researchers believed that the interaction was mediated by TCE itself rather than its metabolites. TCE can also potentiate hepatic damage produced by low (10 ppm) concentrations of carbon tetrachloride in ethanol pretreated rats (Ikatsu and Nakajima 1992). Acetone was a more potent potentiator of carbon tetrachloride hepatotoxicity than was TCE, and acetone pretreatment also enhanced the hepatotoxic response of rats to a TCE-carbon tetrachloride mixture (Charbonneau et al. 1986). The potentiating action of acetone may involve not only increased metabolic activation of TCE and/or carbon tetrachloride, but also possible alteration of the integrity of organelle membranes. Carbon tetrachloride-induced liver necrosis and lipid peroxidation in the rat has been reported to be potentiated by 1,2- dichloroethane in an interaction that does not involve depletion of reduced liver glutathione, and that is prevented by vitamin E (Aragno et al. 1992). 

Nutritional status can also influence the toxic potency of carbon tetrachloride. Animal studies have clearly demonstrated that brief fasting or consumption of diets low in antioxidants (vitamin E, selenium, methionine) can lead to increased carbon tetrachloride hepatotoxicity. The same may be true for humans, although this is not known for certain. Another aspect of nutritional status affecting carbon tetrachloride toxicity is hepatic energy status. Hepatic ATP levels might influence the ultimate outcome of toxicity (low levels may inhibit recovery mechanisms). 

Hooser, S.B., Rosengren, R.J., Hill, D.A., Mobley, S.A. Sipes, I.G. (1994) Vitamin A modulation of xenobiotic-induced hepatotoxicity in rodents. Environ. Health Perspect., 102 (Suppl. 9), 39-43... 

Wijeweera, J.B., Gandolfi, A.J., Badger, D.A., Sipes, I.G. Brendel, K. (1996) Vitamin A potentiation of vinylidene chloride hepatotoxicity in rats and precision cut rat liver slices. Fundam. appl. Toxicol., 34, 73-83... 

A wide range of substances can cause hepatotoxicity. Even an essential vitamin, vitamin A,... 

The liver hepatomegaly, hyperlipidemia, and histological changes in the liver, including increased coUagen formation. Alcohol potentiates the hepatotoxicity of vitamin A. 

Hepatic Fibrosis/Cirrhosis Fibrosis usually results from chronic inflammation which can be the result of continuous exposure to a variety of hepatotoxic chemicals such as organic arscnicals, vinyl chloride, or high doses of vitamin A (Zimmerman, 1999), chronic ethanol ingestion and nonalcoholic fatty liver disease. Fibrosis usually occurs around the portal area, in the space of Disse, and around the central veins. This results in loss of liver architecture and function. The hepatocytes are replaced with fibrous material and thus there is hepatocyte loss. Periportal fibrosis may lead to portal hypertension. 

The hepatotoxic effects of vitamin A have been reported after consumption of doses of about 100 000 lU/day for periods ranging from weeks to months, as well as after daily supplementation with 25 000 lU for a couple of years, accompanied by an increase in plasma vitamin A concentration to 10 times normal in users of health foods. The smallest daily supplement of vitamin A reported to be associated with liver cirrhosis is 25 000 lU taken for 6 years (15). 

Another feature of vitamin A hepatotoxicity, namely respiratory symptoms caused by hepatic hydrothorax, associated with excessive vitamin A consumption has been reported (49). 

In alcohohcs vitamin A supplementation, which might be a useful therapeutic measure, is complicated by the hepatotoxicity of large doses of the vitamin and the fact that chronic alcohol consumption results in an enhanced susceptibility to this effect (87). 

Alcohol may also act indirectly by causing liver disease, which in turn can affect the capacity of the liver to export vitamin A, thereby enhancing its local toxicity. In alco-hoUcs the carrying capacity of retinol binding protein was increased, even in those with low serum retinol concentrations (97). In such cases, caution in the amount of vitamin A used for therapy is recommended. Similarly, diets that are severely deficient in protein can affect the capacity of the liver to export vitamin A and enhance its hepatotoxicity. 

Minuk GY, Kelly JK, Hwang WS. Vitamin A hepatotoxicity in multiple family members. Hepatology 1988 8(2) 272-5. 

Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 1999 69(6) 1071-85. 

Adverse effects of niacin are most commonly seen when this vitamin is used at pharmacological doses above I g/day in the treatment of dyslipidemia. Notable adverse effects include flushing due to vasodilatation dermatological effects including dry skin pruritus and hyperkeratosis gastrointestinal effects including peptic ulcer,. stomach pain, nausea. and diarrhea elevations in serum uric acid and glucose and hepatotoxicity. ... 

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