Acute liver injury caused by PHMG-hydrochloride or PHMG in combination with either ethanol or diethyl phthalate can be characterized as cholestatic hepatitis with a severe inflammatory component causing high mortality.

We studied the status of proliferation processes (by Ki-67 expression) and biogenesis of free radicals (by chemiluminescence method) in skin biopsy specimens from patients with atopic dermatitis and lichen planus. The index of Ki-67-positive nuclei significantly (p<0.05) increased to 28.40±2.00% in patients with dermatitis and to 32.6±1.9% in patients with lichen planus vs. 8.65±1.31% in the reference sample. Decompensated accumulation of free-radical oxidation products and inhibition of detoxification systems in skin biopsy specimens indicate the development of local oxidative stress. After therapy consisting of two 10-day courses of thymodepressin injections (0.1%, 1.0 ml) over 30 days, normalization of epidermis proliferation was observed. Labeling index in atopic dermatitis and lichen planus significantly decreased (p<0.05) to 17.00±1.87 and 10.9±1.1%, respectively. The role of free radicals in the development of hyperregeneratory processes during dermatoses is discussed.

We studied the protective effect of antioxidant echinochrome A on bleomycin-induced pulmonary fibrosis in rats at the early stages of postnatal ontogeny. Administration of echinochrome A was shown to reduce the severity of bleomycin-induced oxidative stress in the lungs, prevented the development of hypertrophy of interalveolar connective tissue and peribronchial lymphoid infiltration, and normalized the ratio of volume densities of interalveolar septa and alveolar lumen.

Administration of indomethacin (250 mg/kg) to mice was followed by the formation of severe ulcerative and erosive injury to the gastric mucosa, inhibition of DNA synthesis, and development of oxidative stress. Fivefold pretreatment with sedatin (100 microg/kg) decreased the area of indomethacin-induced ulcers and erosions, stimulated DNA synthesis, and reduced the severity of oxidative stress. Non-arginine dermorphin analogue did not stimulate DNA synthesis and had no effect on the degree of oxidative stress. After pretreatment with L-NAME, sedatin did not modulate the synthesis of DNA under conditions of indomethacin-induced injury to the gastric mucosa.

We studied the effect of dalargin and its analogue [Dala]2-leu-enkephalin on the gastric mucosa in indomethacin-receiving animals. Indomethacin treatment was followed by severe injury to the gastric mucosa, decrease in proliferative activity of the epithelium, and stimulation of free-radical processes in gastric tissues. Dalargin significantly decreased the area of erosive and ulcerative lesions, had a normalizing effect on proliferation of epithelial cells, and reduced the degree of oxidative stress. Administration of [Dala]2-leu-enkephalin did not improve the state of the gastric mucosa.

Body weight, absolute and relative heart weight, DNA-synthetic activity of cardiomyocytes, and number of nucleoli in cardiomyocyte nuclei were reduced in newborn albino rats exposed to antennal hypoxia. All these changes developed against the background of oxidative stress. In mature animals, the absolute and relative heart weights were decreased, but the ratio of mononuclear cardiomyocytes in both ventricles was higher than in the control. These changes were accompanied by an increase in the percent of collagen fibers in the myocardial stroma. In the right ventricle, an increase in the cardiomyocyte length to width ratio and a decrease in the number of nucleoli were found. The observed changes can probably induce heart function disturbances under pathological conditions.

Administration of singe doses of lead citrate (200 mg/kg) to pregnant rats (on day 18 of pregnancy) was followed by the appearance of destructive changes in brains at age 40 days, with cysts, foci of gliocyte proliferation, pyknotic neurons, and decreases in NADH and NADPH diaphorase activities in neocortical and hippocampal neurons. Decreases in the density of neurons in the cortex and decreases in cortical thickness were also observed. The intensity of free-radical oxidation in the cortex increased three-fold, along with a 3.9-fold increase in the concentration of lipid peroxides, providing evidence of oxidative stress. The possible mechanisms by which these alterations develop are analyzed.

Objective ― Our study aimed to evaluate the possibility of correcting cardiac consequences of intrauterine hypoxia (IUH) by injecting leu-enkephalin analog, lacking affinity for opiate receptors, in the early postnatal period. Material and Methods ― To model IUH, we placed pregnant Wistar rats in a hypobaric chamber with an oxygen partial pressure of 52 mmHg. The procedure was repeated for 4 h daily over the 15th-19th days of gestation. From the 2nd through the 6th days of their lives, the offspring were injected intraperitoneally with non-opiate leu-enkephalin analog at a dose of 100 μg/kg (NALE: Phe-D-Ala-Gly-Phe-Leu-Arg). This analog did not have affinity for opiate receptors. The 7- and 60-day old offspring of female rats subjected to IUH were investigated. The control group included the descendants of intact animals. We investigated gravimetric indicators, DNA-synthetic activity of cardiomyocytes (CMC) by tritium-labeled thymidine autoradiography method, the size of the CMC nuclei, as well as size and amount of nucleoli in the CMC nuclei. The activity of free radical oxidation was evaluated in cardiac homogenates by chemiluminescence. Results ― In 7-day old rats subjected to IUH vs. control animals, we observed decreases in body mass by 32.6%, in heart mass by 27.3%; in the proportion of 3Н-thymidine labeled CMC nuclei by 32.7% in the left ventricle and by 30.4% in the right ventricle; in the number of nucleoli in the CMC nuclei (in the left ventricle: control – 2.384±0.027, IUH – 2.282±0.027*, p<0.05; in the right ventricle: control – 2.409±0.038; IUH – 2.240±0.012*, p<0, 05). Increase in CML indices of cardiac homogenates was revealed, indicating the activation of free radical oxidation. In 7-day old rats subjected to IUH and administration of the NALE peptide from the 2nd through the 6th days of their lives, the proportion of 3H-thymidine labeled nuclei in the CMC did not differ from the control (in the left ventricle: control – 12.79±0.89%, IUH + NALE – 10.98±0.95%, p>0.05; in the right ventricle: control – 11.61±0.78%; IUH + NALE – 11.26±0.58%, p>0.05). The number of nucleoli in the CMC nuclei of the left and right ventricles in the heart of 7-day old animals in the IUH + NALE group did not differ from the control too. The CML indices of heart homogenates in the IUH + NALE group were significantly lower than those in the IUH group. In 60-day old male rats exposed to IUH, there was a decrease in heart mass by 18.5%, sizes of CMC nuclei by 7.5% and 16.1% in the left and right ventricles, respectively, and in the total nucleoli area in the CMC nuclei of the left ventricle (control – 3.953±0.085; IUH – 3.372±0.078*; p<0.05). In 60-day old male rats subjected to IUH and injections of the NALE peptide from the 2nd to the 6th days of their lives, heart mass (control – 692.73±26.81 mg; IUH + NALE – 631.0±29.79 mg; p>0.05) and the size of the CMC nuclei of the right ventricle (control – 54.25±0.84; IUH + NALE – 55.24±0.94; p>0.05) did not differ significantly from the control. The size of the nuclei, the number and size of the nucleoli in the CMC of the left ventricle, as well as the area of the nucleoli in the CMC of the right ventricle in 60-day old male rats of the IUH + NALE group significantly exceeded control group values. Conclusion ― Administration of the NALE peptide to albino rats subjected to IUH normalized DNA-synthetic activity and the number of nucleoli in the nuclei of CMC in 7-day old animals, and also reduced the severity of oxidative stress in the heart tissue. In 60-day old albino male rats exposed to IUH, injecting NALE from the 2nd to the 6th days of their lives eliminated declines in heart mass and sizes of the CMC nuclei and nucleoli, and also led to an increase in the values of the nucleus-and-nucleolus complex indices compared with the control.