Atrophy, liver

As regards toxicity, pyrazole itself induced hyperplasia of the thyroid, hepatomegaly, atrophy of the testis, anemia and bone marrow depression in rats and mice (72E1198). The 4-methyl derivative is well tolerated and may be more useful than pyrazole for pharmacological and metabolic studies of inhibition of ethanol metabolism. It has been shown (79MI40404) that administration of pyrazole or ethanol to rats had only moderate effects on the liver, but combined treatment resulted in severe hepatotoxic effects with liver necrosis. The fact that pyrazole strongly intensified the toxic effects of ethanol is due to inhibition of the enzymes involved in alcohol oxidation (Section 4.04.4.1.1). 

Pain, headache, asthenia, abdominal pain, chest pain, flu symptoms, fever, liver toxicity, insomnia, nausea, constipation, testicular atrophy, dyspnea, pain, asthenia... 

HCDD. Administration of 0.1-100 / g HCDD/kg/day was associated with a dose-related decrease in maternal weight-gain during gestation. Gross necropsy examination at the time of cesarean section revealed evidence of maternal toxicity only among dams receiving 100 /xg/kg/day (pale, friable liver 3/20 dams serous atrophy of fat, 1/20 dams). 

The quantity and organization of the mucosa are critical determinants of GIT functions. Feeding chicks and rats diets with tannins causes mucosal atrophy and villus shortening, with liver damage, and decreases growth and survival... 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is distinctly rare and even more devastating clinically than deficiencies of glucose-6-phosphatase or fructose-1,6-bisphosphatase. PEPCK activity is almost equally distributed between a cytosolic form and a mitochondrial form. These two forms have similar molecular weights but differ by their kinetic and immunochemical properties. The cytosolic activity is responsive to fasting and various hormonal stimuli. Hypoglycemia is severe and intractable in the absence of PEPCK [12]. A young child with cytosolic PEPCK deficiency had severe cerebral atrophy, optic atrophy and fatty infiltration of liver and kidney. 

Defects of the Krebs cycle. Fumarase deficiency was reported in children with mitochondrial encephalomyop-athy. Usually, there is developmental delay since early infancy, microcephaly, hypotonia and cerebral atrophy, with death in infancy or early childhood. The laboratory hallmark of the disease is the excretion of large amounts of fumaric acid and, to a lesser extent, succinic acid in the urine. The enzyme defect has been found in muscle, liver and cultured skin fibroblasts [16]. 

Chromium has proved effective in counteracting the deleterious effects of cadmium in rats and of vanadium in chickens. High mortality rates and testicular atrophy occurred in rats subjected to an intraperitoneal injection of cadmium salts however, pretreatment with chromium ameliorated these effects (Stacey et al. 1983). The Cr-Cd relationship is not simple. In some cases, cadmium is known to suppress adverse effects induced in Chinese hamster (Cricetus spp.) ovary cells by Cr (Shimada et al. 1998). In southwestern Sweden, there was an 80% decline in chromium burdens in liver of the moose (Alces alces) between 1982 and 1992 from 0.21 to 0.07 mg Cr/kg FW (Frank et al. 1994). During this same period in this locale, moose experienced an unknown disease caused by a secondary copper deficiency due to elevated molybdenum levels as well as chromium deficiency and trace element imbalance (Frank et al. 1994). In chickens (Gallus sp.), 10 mg/kg of dietary chromium counteracted adverse effects on albumin metabolism and egg shell quality induced by 10 mg/kg of vanadium salts (Jensen and Maurice 1980). Additional research on the beneficial aspects of chromium in living resources appears warranted, especially where the organism is subjected to complex mixtures containing chromium and other potentially toxic heavy metals. 

Adult males, age 16 weeks, fed pelleted commercial duck diet for 10 weeks diet formulated to contain 24% lead-contaminated sediment (3400 mg Pb/kg DW sediment = 816 mg Pb/kg DW total diet) 1 of 10 died vs. none in controls survivors had atrophied breast muscles, green staining of feathers around the vent, viscous bile green staining of the gizzard lining, and renal intranuclear inclusion bodies. Blood had 6.1 mg Pb/kg FW, liver had 2.8 mg Pb/kg FW, and feces had 1660 mg Pb/kg DW 61... 

Gy, 5 species Dead rodents had histopathology of lymph nodes, thymus, bone marrow, liver, lung, and gonads male survivors had atrophied testes 26... 

Classic beri-beri, rarely seen in the United States and Europe, except in alcoholism (P4), is endemic in the Far East because of the prevalent diet of decorticated rice (F6). It occurs in two forms wet beri-beri, characterized by edema and cardiovascular symptoms (G6), and dry beri-beri with peripheral neuritis, paralysis, and atrophy of the muscles. Conditions which may predispose to deficiency by increasing thiamine requirements are pregnancy (see section 2.4), and lactation, hyperthyroidism, malignant disease, febrile conditions, increased muscular activity, high carbohydrate diets, and parenteral administration of glucose solutions. A constant supply of thiamine is required for optimal nutrition because storage in the liver and elsewhere is limited. Thiamine is synthesized by bacteria in the intestinal tract of various animals, but this is not a dependable source for man. 

These data are insufficient to clarify the precise relationship among testicular atrophy, high testosterone, and low zinc, but the study authors speculated that testicular atrophy may depend on phthalate induction of elevated levels of testosterone in the testis, accompanied by reduced zinc levels in both the testis and the liver. 

Townsend E. 1939. Acute yellow atrophy of the liver. Two cases, with one recovery. Br Med J 2 558-560. 

Only one report of human death attributed to 1,4-dichlorobenzene exposure has been located in the literature. A 60-year-old man and his wife died within months of each other due to acute yellow atrophy of the liver (also known as massive hepatic necrosis or fulminant hepatitis) (Cotter 1953). Their home had been "saturated" with 1,4-dichlorobenzene mothball vapor for a period of about 3-4 months, but no air measurements were available. Clinical symptoms included severe headache, diarrhea, numbness, clumsiness, slurred speech, weight loss (50 pounds in 3 months in the case of the husband), and jaundice. The wife died within a year of the initial exposure however, it was not clear if 1,4-dichlorobenzene was the primary cause of death. This case study did not address whether these individuals consumed excessive amounts of alcohol or had previous medical problems, such as a chronic liver infection. 

The second case is that of a 34-year-old woman who had been exposed to vapors of 1,4-dichlorobenzene at work and became acutely ill with nausea and vomiting, and was hospitalized with hemorrhage from the gastrointestinal tract (Cotter 1953). The physical and chemical findings led to the diagnosis of subacute yellow atrophy and cirrhosis of the liver from 1,4-dichlorobenzene exposure. No further information was located. 

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