Liver lipid metabolism in T-2 toxicosis

The acute effects of oral administration of a single dose of T-2 toxin (2.0 mg/kg body wt) to rats on whole liver lipid metabolism were studied at 8, 16 and 24 h post-treatment. Administration of T-2 toxin significantly increased liver and microsomal total lipids, free cholesterol, esterified cholesterol and triglycerides initially at 8 h, which subsequently returned to control values at 24 h. However, no significant alterations were observed in the contents of whole liver and liver microsomal total phospholipids and phosphatidyl choline, except that phosphatidyl ethanolamine and sphingomyelin + lysophosphatidyl ethanolamine contents in liver at 16 and 24 h and sphingomyelin + lysophosphatidyl ethanolamine content in liver microsomes at all three periods were significantly lower. The incorporation of 1-¹⁴C-acetate into whole liver and liver microsomal total lipids was reduced at 16 and 24 h post feeding. However, the incorporation of 1-¹⁴C-acetate into liver and microsomal free cholesterol, esterified cholesterol and triglycerides was significantly higher at 8 h, subsequently returning to the control value at 24 h; incorporation was significantly lower even into microsomal triglycerides. The incorporation of 1-¹⁴C-acetate into liver and its microsomal total phospholipids, phosphatidyl choline, phosphatidyl ehtanolamine and sphingomyelin + lysophosphatidyl ethanolamine, was significantly decreased at all three periods post toxin treatment. The results suggested that T-2 toxin inhibited the incorporation of ¹⁴C-acetate mainly into liver and its microsomal phospholipids and their subfractions in rats.     

Lipid spectrum in different tissues of MT81 toxin-treated mice

The effects of different intraperitoneal doses of MT81 (2.5 mg/kg, 5.0 mg/kg and 7.5 mg/kg, respectively) for a 2-week, 4-week and 6-week treatment on concentration of total lipid and its different fractions of liver, brain, kidney, testis and serum in mice were studied. The following were measured: total lipid, free and total cholesterol, total phospholipid and its fractions (lecithin, lysolecithin, phosphotidylethanolamine and lysophosphotidylethanolamine), triglyceride, free fatty acid; lipase activity was also measured in serum, liver, and testis. Ascorbic acid content of testis was also measured. This mycotoxin (MT81) caused biochemical disorders of the tissues. Total cholesterol, free cholesterol, total phospholipid and its fractions, triglycerides and total lipids were elevated significantly in liver, serum, kidney and testis of toxin-treated animals. Free fatty acid increased significantly at a later stage in serum and remained constant in other tissues of toxin-treated mice. All the lipid fractions except total phospholipid and its fractions remained constant in brain of treated animals; total phospholipid and its fractions decreased significantly in brain of toxin-treated mice. Lipase activity decreased significantly in serum, liver and testis of treated mice. Ascorbic acid content of testis of treated animals increased significantly. Such disorders of lipid concentrations in the aforesaid tissues might be associated with the CNS depressant action and structural and functional toxicity of other tissues induced by the MT81 toxin.     

Effect of oral administration of T-2 toxin on glutathione shuttle enzymes, microsomal reductases and lipid peroxidation in rat liver

Effects of T-2 toxin on liver lipid peroxidation, glutathione shuttle enzymes and microsomal reductases have been studied in rats at 8, 16 and 24 hr after feeding a single dose of toxin (2.0 mg/kg) and at 7, 14 and 21 days after feeding of toxin (0.75 mg/kg) daily. Feeding of a single dose of T-2 toxin caused significant increase in liver lipid peroxidation in rats at 8, 16 and 24 hr post treatment. The liver lipid peroxidation was also significantly increased at 14 and 21 days after feeding of 0.75 mg/kg of T-2 toxin daily to rats. The activities of liver GSH-shuttle enzymes, i.e. glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, were significantly higher in rats after both feeding schedules of T-2 toxin. NADPH-cytochrome c reductase activity was significantly lower at 8, 16 and 24 hr in liver of rats fed a single dose of T-2 toxin, whereas NADH-cytochrome b5 reductase was significantly higher until 16 hr and then declined below normal at 24 hr post treatment. In rats fed multiple doses of T-2 toxin, both liver microsomal reductases were significantly reduced. These results suggest that T-2 toxin/or its metabolites in the liver may be involved in the generation of free radicals which cause the observed increase in lipid peroxidation.     

Effects of T-2 toxin gavage on the synthesis and contents of rat-liver macromolecules

Effects of oral administration of T-2 toxin (0.75 mg/kg body weight/day) for 7, 14 or 21 days on the liver and plasma of young male rats were studied. A significant decrease in body weight and an increase in liver weight were observed in rats treated with T-2 toxin. Liver protein and glycogen levels were significantly lower than in controls after 21 days of treatment, but no significant differences were observed after 7 or 14 days. Levels of RNA in liver were significantly increased after 7, 14 and 21 days of treatment whereas liver DNA levels were significantly lower than in controls at each time interval. Liver microsomal protein was significantly decreased after 14 and 21 days, but microsomal RNA contents were significantly increased at 7 days and significantly decreased at 21 days. The levels of serum protein at 7, 14 and 21 days and of blood glucose at 14 and 21 days were significantly lower in T-2 toxin-treated rats. The levels of incorporation of [14C]leucine and [3H]uridine into liver protein and RNA, and into liver microsomal protein and RNA, were higher than in controls at 7 days, but then decreased. The incorporation of [3H]thymidine into liver DNA was not significantly altered in animals treated with the toxin.     

Cardiovascular pathology induced by passive transfer of splenic cells from syngeneic rats treated with T-2 toxin

Mononuclear cells were separated from spleens and lymph nodes of Lewis rats treated 5 weeks previously with repeated small doses of T-2 toxin or solvent only. The cells from each site were then injected intraperitoneally into 4 groups of syngeneic Lewis rats. The animals injected with spleen cells from T-2 toxin-treated donors developed marked cardiovascular changes which were similar to those due to T-2 toxin itself. Rats injected with lymph node cells as well as those given each kind of cell from solvent-treated donors showed only occasional mild vascular changes. The changes seen after splenic cell transfer may be due to superinduction of interleukin 2 by T-2 toxin.     

Influence of T-2 toxin on BCG vaccine efficacy against murine pulmonary tuberculosis

Unvaccinated mice were treated with T-2 toxin either 6 days before or 1 day after exposure to aerosols of virulent Mycobacterium tuberculosis. Mice were also treated with T-2 toxin 6 days before vaccination with Mycobacterium bovis (BCG). There was a T-2 toxin mediated increase in the number of viable vaccine organisms recovered from the spleens of toxin-treated mice at 3 weeks after vaccination, and splenomegaly at post-vaccine weeks 3 through 5. At the seventh week after vaccination, toxin-treated vaccinated, toxin-treated non-vaccinated, vaccinated, and untreated mice were exposed to aerosols of viable M tuberculosis. The number of viable mycobacteria in the lungs was determined at weeks 3, 5, 7, and 9 after pulmonary infection. The number of viable tubercle bacilli recovered from the lungs of vaccinated mice was significantly lower than from unvaccinated mice. However, T-2 toxin-treatment did not alter the vaccine efficacy.     

Influence of castration and testosterone propionate on prostatic and seminal vesicular lipids in mature monkeys

The effect of castration and administration of testosterone propionate (TP) has been studied in mature monkeys in relation to prostatic and seminal vesicular lipids to castrates on prostatic and seminal vesicular lipids were studied in mature monkeys. Castration decreased prostatic total lipid, total phospholipids and total glyceride glycerols. Among neutral lipid classes only diacyl glycerol was decreased due to castration. Similarly among phospholipid classes, phosphatidyl choline and ethanolamine were decreased. A marked decrease in the seminal vesicular total lipid, total phospholipids, total cholesterol and total glyceride glycerol were observed due to castration. Mono and diacyl glycerols and phosphatidyl choline and ethanolamine also registered a significant decrease after castration. Administration of TP to castrates brought back all the lipid classes to normal level which showed a decrease due to castration. However, TP treated to castrates on both seminal vesicles and prostates had no effect on other classes of lipids which were unaltered by castration. The present study reveals that lipid metabolism in the male accessory sex organs is under androgenic control. Nevertheless, the influence of testicular androgen is specific to different classes of lipids as a number of phospholipids and neutral lipid classes were resistant to castration or administration of TP.     

Hypoglycaemic and hypolipaemic effects of Cyamopsis tetragonoloba (guar) in normal and diabetic guinea pigs

Information available in literature is contradictory regarding the glycaemic and cholesterolaemic activities of various legume proteins. Present work deals with the study of the effect of 'Guar' feeding on serum total lipids, free and esterified cholesterol, triglycerides and phospholipids. Normal and alloxan induced diabetic guinea pigs were kept on the whole seed diet of 'Guar' for four weeks. Blood sugar and total lipid levels were found to be decreased significantly in normal and as well as diabetic animals; free and esterified cholesterol levels were also observed to be lowered significantly in normals, whereas esterified fraction alone was found to be lowered in diabetics. Significant fall in the levels of other lipids i.e., triglycerides, phospholipids and total lipids was also noticed.     

Effect of T-2 toxin on in vivo lipid peroxidation and vitamin E status in mice.

The effects of an acute administration of T-2 toxin on vitamin E status and the corresponding degree of lipid peroxidation, as determined by the plasma and organ content of malondialdehyde (MDA), was studied in mice. The effects of T-2 toxin administration on the body weight and weights of liver, spleen and thymus were also assessed. T-2 toxin was administered in doses ranging from 1 to 6.25 mg/kg body weight, depending on the experiment, while the dietary content of vitamin E ranged from near 0 to 5000 IU/kg. There was a significant decrease in vitamin E content of plasma after the administration of the toxin with the concentrations remaining low for periods as long as 48-72 h. MDA content of liver increased significantly after 24-48 h of toxin administration in contrast to the controls. However, MDA levels returned to the control range after 72 h. The concentrations of MDA in liver were inversely related to the vitamin E content of the diet, and were always higher for the toxin-treated animals (significant linear regression between MDA content of liver and the log10 of vitamin E content of the diet). Weights of spleen and thymus decreased after T-2 toxin administration; however, the weight of liver either increased or did not change in the different experiments. In conclusion, T-2 toxin treatment of mice increased lipid peroxidation in the liver as measured by MDA production. This process was maximal after 48 h of T-2 challenge, and decreased thereafter. Plasma alpha-tocopherol levels decreased as soon as 6 h after the toxin challenge, while MDA did not increase until there was a severe depletion of vitamin E. These changes were accompanied by decrease in weight of spleen and thymus.     

Effect of scorpion (Leiurus Quinquestriatus H and E) venom on lipid metabolism.

Injection of rats with a sublethal dose (200 μg per kg) of Leiurus quinquestriatus venom, induces an increase in the total lipid, cholesterol and phospholipid content of the liver. In the serum an increase in the free and esterified cholesterol, esterified fatty acids, phosphatidylcholine, phosphatidylethanolamine and a decrease in free fatty acids, sphingomylin and lysolecithin was demonstrated. An increase in the albumin, alpha₁-and alpha₂-globulins, and a decrease in the beta and gamma globulins of the serum was also observed.     

Delay of the Onset of Puberty in Female Rats by Prepubertal Exposure to T-2 Toxin

Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 μg/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG) axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of the present study provide valuable information for the health risk assessment in children.     

Effect of T-2 toxin on regional blood flow and vascular resistance in the conscious rat

The acute effect of T-2 toxemia on local blood flow and vascular resistance in hindquarter, mesenteric, and renal vascular beds was continuously measured by the directional pulsed Doppler technique in conscious, male Sprague-Dawley rats. Intravenous injection of T-2 toxin (1 mg/kg) in the conscious rat reduced blood flow and increased vascular resistance in all blood vessels studied but had no significant effect on mean arterial pressure or heart rate. The blood flow in hindquarters gradually decreased to a minimum of -77 +/- 9% (mean +/- SE) 6 hr after the toxin injection. The hindquarter vascular resistance concomitantly increased to a maximum value of +323 +/- 69% above the resistance before toxin administration. Mesenteric and renal blood flow initially increased (slightly) and then gradually decreased. The maximum drop of blood flow, -90 +/- 13% and -76 +/- 13% for the mesenteric and renal vascular beds, respectively, was achieved 4 hr after T-2 toxin injection and the blood flow values remained low for up to 6 hr. Simultaneously with the impairment of blood flow the mesenteric and renal vascular resistance increased to reach the maximal values of +404 +/- 99% and +556 +/- 15%, respectively. In addition, plasma renin activity was markedly elevated (+653 +/- 160%) at the time of reduced renal blood flow. Intravenous injection of the same value of vehicle (10% ethanol in saline) had no significant effect on any of the cardiovascular variables studied. Two of five rats in the T-2 toxin-treated group died within 5 hr after the T-2 toxin injection and only one animal survived 24 hr while all the control animals survived over 24 hr. The results suggest that strong vasoconstriction in skeletal muscle, mesenteric, and renal vascular beds leads to impairment of local blood flow. The ischemia in vital organs together with the earlier reported decrease in cardiac output by T-2 toxin might then be the cause of rapid death in acute T-2 toxemia.     

Effect of 17 alpha-ethinyl estradiol on the blood serum lipid indices of rats

The administration of 17-ethinyl estradiol (0.25 mg/kg) to male Wistar rats caused on the 3rd day a decrease of the levels of free and esterified cholesterol, blood serum triglycerides and also a reduction of the content of esterified cholesterol with respect to total cholesterol while the lecithin-cholesterol-acyltransferase activity appeared to be unchanged. The effect of ethinyl estradiol on blood lipid parameters against the background of lipemia induced by triton WR 1339 was reduced.     

Changes of lipid spectrum in different tissues of Furadan-treated mice

The effects of multiple intraperitoneal doses of Furadan (0.125 mg/kg, 0.25 mg/kg and 0.50 mg/kg, respectively) for the 2nd week, 4th week and 6th week of treatment on the concentrations of total lipid and its different fractions and lipase activity in mice were studied. The following were measured in liver, kidney, brain and serum; total lipid, cholesterol (total and free), phospholipid (total and its fractions--lecithin, lysolecithin, phosphatidyl ethanolamine and lysophosphatidylethanolamine), triglyceride, free fatty acid. Lipase activity was measured in liver and serum. Furadan caused biochemical disorders of the tissues. All the aforesaid lipid fractions (except free fatty acid) are elevated significantly in liver, kidney and serum of Furadan-treated mice. Free fatty acid increased significantly in serum and remain constant in other tissues of pesticide-treated mice. All the lipid fractions except phospholipid and its fractions remained constant in brain of treated mice; total phospholipid and its fractions decreased significantly in brain of treated mice. Lipase activity decreased significantly in liver and serum of treated mice. Such disorders of lipid levels in the aforesaid tissues might be associated with CNS depressant action and structural and functional toxicity of other tissues induced by Furadan.     

Untersuchungen über die Phospholipoide des Kalbsthymus

Investigations of the Phospholipids of Calf Thymus The thymus of freshly slaughtered calves was found to contain 4,1 % of lipids, of which 1 – 3 % consisted of hydrocarbons, 66 – 69 % of neutral lipids and 22,5 – 24 % of phospholipids. In the latter fraction were identified: phosphatidyl choline, phosphatidyl ethanolamine, sphingomyelin, phosphatidyl serine and phosphatidyl inositol. The main components are: phosphatidyl choline (0,56 %), phosphatidyl ethanolamine (0,27 %) and sphingomyelin (0,12 %). Their analysis was done by Kieselgel/magnesium silicate thinlayer chromatography using the colorimetric determination of phosphorus.     

Long-term effects of a single oral dose of polybrominated biphenyls on serum and liver lipids in rats

Adult (5 months) male Sherman strain rats received a single dose of either 0 or 500 mg polybrominated biphenyls (PBB) in corn oil/kg body weight by stomach tube. After an 18-month recovery period, serum and liver samples were examined. The primary serum lipid response was an increase in cholesterol (both free and esterified) and in total phospholipids. The percentage of esterified cholesterol was not significantly different from that of the controls, and no significant differences in the cholesterol ester fatty acid composition were observed. Serum triglycerides were also unaffected. In the PBB-dosed animals, the total hepatic fatty acids contained significantly less palmitic acid and more stearic acid, consistent with an increase in palmitic acid chain elongation activity. No significant differences could be detected in the n-3 or n-6 acids except for a slight decline in the content of 22:6 (n-3). Hepatic microsomal phospholipids were slightly higher (per milligram protein) in the PBB-dosed animals, and the cholesterol content was lower. Consequently, the cholesterol-phospholipid ratio was reduced, and microsomes from the latter group appeared to have an altered lipid domain on the basis of steady-state fluorescence anisotrophy measurements. In addition, total hepatic thiobarbituric acid-reactive substances (assayed as malondialdehyde) were significantly increased in the PBB-dosed animals. This observation appeared to reflect an increased susceptibility to peroxidative stress in the latter group, probably resulting from reduced membrane antioxidant concentrations. The PBB-dosed rats had significantly lower serum retinol levels and a reduced content of this vitamin in liver microsomes. Microsomes were also deficient in alpha-tocopherol in the PBB-dosed animals, although serum levels were normal.     

T-2 toxin induced changes in liver and serum enzymes of rats

The effects on liver and serum enzymes of feeding a single dose (2 mg/kg) and daily doses (0.75 mg/kg) of T-2 toxin were studied in young male rats. Sample times were 8, 16 and 24 hr for single dose administration and 7, 14 and 21 days for daily dose administration. T-2 toxin in single and daily doses significantly reduced activities of hepatic glutamate pyruvate transaminase (GPT) and alkaline and acid phosphatases at all the sampling periods. In both feeding trials, levels of serum GPT increased, while that of acid and alkaline phosphatases significantly decreased at all the sampling times. This study indicates that the liver is affected by feeding T-2 toxin to rats.     

Prevention of T-2 toxin-induced morphologic effects in the rat by highly activated charcoal

The efficacy of a highly activated charcoal in preventing the morphologic effects of T-2 toxin was examined in female rats. T-2 toxin at 25 mg/kg (6×LD₅₀) was given orally to all rats. Half the rats also received the charcoal, at a dose of 9 ml/kg and a concentration of 104 mg/ ml, while the other half received water. A charcoal-treated rat (T-2 toxin + charcoal) was killed at the time of death of each positive control animal (T-2 toxin alone). Severe necrosis was seen in the spleen, thymus, stomach, small intestine, liver and adrenal glands of the positive controls (T-2 toxin alone). Lesions were absent or minimal in the paired charcoal-treated rats (T-2 toxin + charcoal).     

Role of lipid peroxidation in the toxicity of T-2 toxin

A. , G. , B. and W. . Role of lipid peroxidation in the toxicity of T-2 toxin. Toxicon 25, 1321 – 1328, 1987.—Recent reports suggest that lipid peroxidation may be involved in the toxicity of T-2 toxin. In the present study the influence of T-2 toxin on two parameters of lipid peroxidation was examined: the formation of thiobarbituric acid reactive material in isolated hepatocytes and liver homogenates from rats and ethane exhalation in vivo. In isolated hepatocytes there was no significant increase in thiobarbituric acid reactive material, neither after addition of T-2 toxin in vitro nor when the toxin had been applied to the rats 15 hr before preparation of hepatocytes. In liver homogenates the amount of thiobarbituric acid reactive material was increased up to 50% over the controls, depending on the dose of T-2 toxin. The increased values are difficult to interpret, because the extent of the increase depends on the method used for determination of thiobarbituric acid reactive material. Measuring another parameter of lipid peroxidation, i.e. ethane exhalation, there was no difference between the T-2 toxin treated rats and the controls whereas carbon tetrachloride treated rats exhaled high amounts of ethane. These results suggest that lipid peroxidation does not play a major role in T-2 toxin toxicity.     

Hepatotoxicity in albino rats exposed to n-octane and n-nonane

Effects of n-octane and n-nonane (1 ml per kg body weight daily) on hepatic and serum enzymes, which reflect abnormal liver function and concentration of lipid and nucleic acid (serum and liver), were studied after 2 and 7 days intraperitoneal administration to albino rats. Decreased activities of serum acetylcholine esterase and carboxyl esterase were observed, together with an increase in FDP aldolase activity. Significant decrease in the concentration of albumin, total protein, and total and esterified cholesterol in serum have been noted after n-octane and n-nonane administration for 7 days. Also, free cholesterol content of liver was elevated significantly after solvents exposure.