Disturbance of microsomal detoxication mechanisms in liver by chlorophenol pesticides

The pesticide pentachlorophenol known as an uncoupler of mitochondrial oxidative phosphorylation was shown to disturb liver microsomal detoxication functions by a selective inhibition of the terminal oxygenation enzyme P-450. At lower concentrations the flavin moiety of this enzyme chain is not inhibited but rather is stimulated, whereby a qualitative shift in detoxication of aromatic amines from C-oxygenation to N-oxygenation is obtained. The effects were due to the pentachlorophenol itself and not to a metabolite.Similar effects of varying strength were also obtained with other chlorophenol pesticides; 2,4,di-, 2,4,6,-tri and 2,3,4,6-tetrachlorophenol, di- and hexachlorophen, tri- and nonachloro-2-hydroxydiphenyl ethers.The relevance of these findings to the possible synergistic influence of chlorophenols on the carcinogenic effects of polyaromatic amines and hydrocarbons is discussed.     

Dynamics of antioxidant protection and detoxication processes affected by strobilurin fungicides in the liver of cyprinids

The effects of three fungicides of a new generation were studied for cyprinid young of the year. Acute toxicity (96 h of exposure) has an extremely negative effect on fish. The minimal lethal concentrations of fungicides (LC₁₆) caused metabolic disorders and the activation of detoxication processes in carp liver at the very beginning of exposure to toxins (24–96 h). The increase in exposure led to the lipid peroxidation process intensifying and to a simultaneous decrease in the effectiveness of antioxidant protection (AOP) and detoxication. The inhibition of the activity of superoxide dismutase, catalase, and glutathione-S-transferase was observed, and the depletion of reduced glutathione reserves in the liver was found. The progression of intoxication over 15 days resulted in morphological and functional alterations in the fish liver and death in 49% of fish exposed to toxins.     

Status of the detoxication function of the liver after vagal denervation

In 14 and 25 days of bilateral subdiaphragmatic+ vagotomy perimeter of the endoplasmic reticulum (EPR) of hepatocytes, content of the enzyme (cytochrome R-450) built into the membrane in microsomal fractions, speed of hydroxylation of substrates and oxygen absorption decreased and the section area of EPR and duration of the hexonal sleep increased. The results demonstrate certain disturbances of the detoxication function of the denervated liver.     

甲亢性肝损害116例临床分析

目的探讨甲状腺功能亢进症（甲亢）肝损害的临床特点。方法收集228例甲亢患者的临床资料,分为肝损害组及无肝损害组,对两组患者的年龄、性别、甲亢病程、肝功能及甲状腺功能等指标进行分析比较。结果 228例甲亢患者中发生肝损害116例,发生率为50.72%。甲亢患者的性别与甲亢性肝损害的发生率无相关性;而年龄越大甲亢性肝损害发生率越高,病程越长甲亢性肝损害发生率也越高。甲亢性肝损害患者甲状腺功能指标TT4、FT3明显高于甲亢肝功能正常的患者,差异有统计学意义（P〈0.05）;肝功能测定以ALT、ALP升高多见。结论甲亢性肝损害的发病率较高,病情的严重程度与年龄、病程、甲状腺激素水平有密切关系;建议临床医生对初诊及复诊甲亢患者进行肝功能常规测定,以便合理选用治疗方案,使甲亢性肝损害得以及早治疗。     

Estrogen metabolism in hyperthyroidism and in cirrhosis of the liver.

Estrogen metabolism was studied in spontaneous hyperthyroidism (Graves disease) and in alcoholic cirrhosis of the liver. The plasma concentration of estradiol-17beta (PCE2) was increased in men with hyperthyroidism. Although the metabolic clearance rate of estradiol-17beta (MCRE2) was reduced, the production rate (PR) of the steroid was increased above normal. The MCRE2 was also decreased in women with hyperthyroidism but the PCE2 and PRE2 was unchanged from normal. The conversion ratio of estradiol-17beta (CRE2E1) was increased in both hyperthyroid men and women. The PCE2 was significantly increased in men with cirrhosis of the liver. The MCRE2 was normal and this resulted in an increase in the PRE2 in this disorder. The CRE2E1 was significantly higher than normal. The plasma concentration of estrone (E1) was elevated in men with both disorders.     

Formation of lamellar bodies in rat liver mitochondria in hyperthyroidism

In the present work, ultrastructural changes of rat liver mitochondria in hyperthyroidism were studied. Hyperthyroidism was induced in male Wistar rats by daily administration of 100 μg thyroxin per 100 g body weight for 5 days. The level of triiodothyronine and thyroxine increased 3- and 4-fold, respectively, in comparison with the same parameters in the control group, indicating the development of hyperthyroidism in experimental animals. It was found that under this experimental pathology 58% of the mitochondria are swollen, with their matrix enlightened, as compared to the control. In 40% of the profiles, the swollen mitochondria in the liver under hyperthyroidism exhibited rounded mono- or multilayer membrane structures, called lamellar bodies (LBs), presumably at different stages of their development: from the formation to the release from the organelles. Most LBs were located in the mitochondria near the nuclear zone (27%), while their number was reduced in the part of the cell adjacent to the plasma membrane. In a number of swollen mitochondria the cristae were shown to change their orientation, being directed radially toward the center of the mitochondria. We suggested that it is the first stage of formation of LBs. The second stage can be attributed to the formation of monomembrane structures in the center of the organelles. The third stage is characterized by the fact that the membrane of the lamellar bodies consists of several layers, and in this case the bodies were located closer to the outer mitochondrial membrane. The evagination of the outer mitochondrial membrane and its connection with lamellar structure can be recognized as the fourth stage of formation of LBs. At the fifth stage the developed lamellar formations exited the mitochondria. At the same time, following the exit of LBs from the mitochondria, no damage to the mitochondrial membrane was registered, and the structure of the remaining part of the mitochondria was similar to the control. The nucleus of the hepatocyte also underwent structural changes in hyperthyroidism, exhibiting changes in the membrane configuration, and chromatin condensation. The nature and structure of the LBs, as well as their functional role in the liver mitochondria in hyperthyroidism, require further investigation.     

Comparative detoxication. The detoxication of aromatic acids by invertebrates: detection of agmatine conjugates in scorpions

1. Benzoic acid and p-nitrobenzoic acid were converted in the scorpion Palamnaeus into N(1)-benzoylagmatine and N(1)-p-nitrobenzoylagmatine. 2. Some benzoyl- and p-nitrobenzoyl-arginine were also formed and these compounds were probable precursors of the agmatine derivatives. 3. p-Nitrobenzoyl- and p-aminobenzoyl-arginine were formed in millipedes dosed with the aromatic acids. 4. Woodlice excreted p-amino- and p-nitro-benzoic acid as their glycine conjugates and no conjugation could be found in the crab Gecarcinus and a freshwater crayfish Astacus.     

Experimental hyperthyroidism causes inactivation of the branched-chain alpha-ketoacid dehydrogenase complex in rat liver

Hyperthyroidism induced by 3-day treatment of rats with thyroid hormone (T(3); 3,5,3'-triiodothyronine) at 0.1 or 1 mg/kg body wt/day resulted in a reduced activity state (% of enzyme in its active, dephosphorylated state) of the hepatic branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. One treatment with 0.1 mg T(3)/kg body wt caused a significant effect on the activity state of BCKDH complex after 24 h, indicating that the reduction of the activity state was triggered by the first administration of T(3). Hyperthyroidism also caused a stable increase in BCKDH kinase activity, the enzyme responsible for phosphorylation and inactivation of the BCKDH complex, suggesting that T(3) caused inactivation of the BCKDH complex by induction of its kinase. Western blot analysis also revealed increased amounts of BCKDH kinase protein in response to hyperthyroidism. No change in the plasma levels of branched-chain alpha-keto acids was observed in T(3)-treated rats, arguing against an involvement of these known regulators of BCKDH kinase activity. Inactivation of the hepatic BCKDH complex as a consequence of overexpression of its kinase may save the essential branched-chain amino acids for protein synthesis during hyperthyroidism.     

Effects of hyperthyroidism on synthesis, secretion and metabolism of the VLDL apoproteins by the perfused rat liver

Livers from fed male Sprague-Dawley rats, made hyperthyroid by treatment with triiodothyronine (T3), were isolated and perfused in vitro. T3 (9.6 micrograms/day) was administered by osmotic minipump implanted intraperitoneally. Treatment with T3 for either 7 or 28 days reduced hepatic output of very-low-density lipoprotein (VLDL) and net synthesis of total associated apoproteins. After 7 days treatment, incorporation of [4,5-3H]leucine by livers from hyperthyroid rats into VLDL apo E was reduced while incorporation into apo B100, apo B48, and apo C's did not differ from euthyroid controls. The depressed incorporation of radioactivity into total VLDL protein was accounted for almost entirely on the basis of apo E. Incorporation of leucine into the total lipoprotein apo E isolated in the d less than 1.210 was also diminished by the hyperthyroid state, while that into apo B100, apo B48, and apo C in the total perfusate lipoprotein was similar to that of the euthyroid, as was found for the VLDL. Increased amounts of radioactive apo B100 and apo B48, however, were detected in the HDL fraction isolated from the medium perfusing livers from hyperthyroid rats. Hepatic uptake of VLDL protein and lipid was similar in euthyroid and hyperthyroid rats. Reduction of VLDL lipid and protein in the medium perfusing livers from T3-treated rats, therefore reflects hormonal action on synthesis and secretion, rather than uptake. Since the availability of apo B is thought to be required for secretion of VLDL, our observation suggests that synthesis of apo B is not depressed by treatment with T3 and that apoprotein synthesis is not a significant factor in the decreased output of VLDL by the liver, but that, as reported earlier, the lower output is a consequence of decreased synthesis of TG, the result of a diminished supply of hepatic glycero-3-phosphate in the hyperthyroid. The diminished amount of VLDL protein appears to be accounted for by the decreased quantity of apo E associated with a smaller VLDL particle secreted by livers from T3-treated rats.