Repeated administration of ethambutol in therapeutic dose causes testes alteration and spermatogenesis disruption in Wistar rats.

Ethambutol (EMB) is conventionally used to treat tuberculosis and atypical Mycobacterium infections in combination with other antimycobacterial drugs. Eventually, EMB testicular toxicity has not been explored extensively yet. The aim of the study is to evaluate testicular toxicity of EMB. We explored the impact of EMB on male rats' fertility, testosterone level and germ cells state, testicular pro- and anti-oxidant status and DNA damage, as well as identified EMB effects on cytochrome P-450 2E1 (CYP2E1) both with computer simulation and in vivo. We demonstrated that EMB administration to male rats decreased in epididymal sperm count (19%) and fertility index (53%). These events were accompanied by reduction in serum testosterone content (1.6 times) and appearance of spermatogenic epithelium damages. It was also found in testes the intensification of lipid peroxidation, decrease in reduced glutathione content and changes in DNA fragmentation. Additionally, computer simulation showed direct interaction of EMB with CYP2E1 active site and heme. On the top of this, we demonstrated that level of testicular CYP2E1 messenger RNA in EMB-treated rats was increased 8.7 folds and p-nitrophenol hydroxylase activity in testes rose three folds. As this shows, EMB-caused CYP2E1 induction, oxidative stress, and apoptosis in the testes contribute to inhibition of steroidogenesis enzymes and spermatogenesis disruption.

[Degree of lipid peroxidation and vitamin E level during the treatment of peptic ulcer]. / Uroven' perekisnogo okisleniia lipidov i kontsentratsiia vitamina E pri lechenii bol'nykh iazvennoi bolezn'iu.

The study of 468 ulcer patients treated by laser irradiation plus choline blocking agents with adjuvant alpha-tocopherol antioxidants (alpha-tocopherol acetate, wild rose and sea-buckthorn oils) provided evidence in favour of the antioxidants addition. Combination of hyperbaric oxygenation (5-6 sessions) or riboxin with choline blocking agents made antioxidants unnecessary. Biochemical findings (vitamin E and malonic dialdehyde concentrations), electron microscopic, ++histo-enzyme and amino acids studies supported the clinical evidence.

[Disorders of the bioenergetics and microcirculation in the gastric mucosa in peptic ulcer with concomitant involvement of the hepatobiliary system]. / Narusheniia bioénergetiki i mikrotsirkuliatsii v slizistoi obolochke zheludka pri iazvennoi bolezni s soputstvuiushchim porazheniem gepatobiliarnoi sistemy.

UNLABELLED: The histological structure, distribution of neutral glycoseaminoglycanes, the content of glycogen in the cells, activity of succinate dehydrogenase, cytochromoxidase, magnesium-dependent ATP-ase, alkaline phosphatase, lactate dehydrogenase were studied in the biopsies of the gastric mucosa removed from the anterior third of the anterior part of its body in 104 patients. RESULTS: essential decrease of the enzymes of oxidative phosphorylation, increased reaction to lactate dehydrogenase, inhibition of enzymes controlling the microcirculation in the gastric mucosa in ulcer disease. These changes deteriorate in elderly patients as well as concomitant diseases of the hepatobiliary system.

Epigenetic changes in the rat livers induced by pyrazinamide treatment.

Drug-induced liver injury, including drug-induced hepatotoxicity during the treatment of tuberculosis infection, is a major health problem with increasingly significant challenges to modern hepatology. Therefore, the assessment and monitoring of the hepatotoxicity of antituberculosis drugs for prevention of liver injury are great concerns during disease treatment. The recently emerged data showing the ability of toxicants, including pharmaceutical agents, to alter cellular epigenetic status, open a unique opportunity for early detection of drug hepatotoxicity. Here we report that treatment of male Wistar rats with antituberculosis drug pyrazinamide at doses of 250, 500 or 1000 mg/kg/day body weight for 45 days leads to an early and sustained decrease in cytosine DNA methylation, progressive hypomethylation of long interspersed nucleotide elements (LINE-1), and aberrant promoter hypermethylation of placental form glutathione-S-transferase (GSTP) and p16(INK4A) genes in livers of pyrazinamide-treated rats, while serum levels of bilirubin and activity of aminotransferases changed modestly. The early occurrence of these epigenetic alterations and their association with progression of liver injury specific pathological changes indicate that alterations in DNA methylation may be useful predictive markers for the assessment of drug hepatotoxicity.

[Histological characteristics of the reactions of cerebral neuroglia in laboratory animals]. / Gistologicheskaia kharakteristika reaktsii neiroglii golovnogo mozga laboratornykh zhivotnykh.

Literature data and the authors' results, concerning structural and functional peculiarities of all varieties of the cerebral neuroglia under effect of a cranial-cerebral trauma, neurotropic chemical products and oxygen insufficiency have been considered. Ideas that neuroglial reactions under the conditions mentioned are proved to be constant and in dependence of certain peculiarities of each case are either progressive or regressive. The reaction degree is mainly proportional to the disturbance power. Nevertheless, certain discrepancies (ariactivity including) can be observed; this is also determined by a combination of prerequisites and by a peculiarity of individual reactivity of the CNS. The greatest stability of astroglia has been stated. Possible variations in relation between changes of neurons and gliocytes are mentioned. Suggestions are made that diffuse-focal progressive reactions of macroglia under conditions of neurotoxicoses can be determined not by proliferation of cells, but by their migration.