Vol 15, No 4 (2024)

BACKGROUND: Modeling toxic pulmonary edema for the purpose of studying the effectiveness of drugs is associated with difficulties in model validation and objectification of drug effectiveness criteria. To confirm the significance of changes in pulmonary coefficients and visual changes in lung tissue, acid-base balance and blood gas analysis are often used to objectify emerging gas exchange disorders.

AIM: To investigate the acid-base composition and blood gases in mice during the progression of toxic pulmonary edema caused by inhalational phosgene exposure.

MATERIAL AND METHODS: Toxic pulmonary edema was induced by exposing mice to phosgene at a dose corresponding to LCt₅₀ in an inhalation chamber. Blood samples were analyzed for acid-base balance and gas parameters, including partial oxygen pressure (pO₂), partial carbon dioxide pressure (pCO₂), total hemoglobin (tHb), oxyhemoglobin (O₂Hb), carboxyhemoglobin (COHb), methemoglobin (MetHb), reduced hemoglobin (RHb), oxygen saturation (sO₂), oxygen concentration (O₂ct), oxygen capacity (O₂cap), partial oxygen pressure at 50 % saturation (P₅₀), total carbon dioxide (tCO₂), true and standard bicarbonate (HCO_3–, SBC), actual and standard base excess (BE_b, BE_ecf), anion gap, lactate, and concentrations of sodium, potassium, chloride, and ionized calcium. Measurements were performed using a gas analyzer at 30 minutes, 3 hours, and 24 hours after exposure initiation.

RESULTS: Significant shifts in blood gas composition and acid-base balance were observed 3 hours after pulmonary edema initiation. These included decreased acid-base balance, reduced oxyhemoglobin levels, lowered oxygen saturation, and elevated partial carbon dioxide pressure, indicating respiratory insufficiency and compensated respiratory acidosis. Major changes in acid-base parameters were observed after 24 hours, with normalization of pH accompanied by increases in true and standard bicarbonate levels, as well as total carbon dioxide content. Changes in actual and standard base excess were observed, reflecting a reduction in base deficit. Electrolyte levels remained unchanged in all experimental groups throughout all observation periods.

CONCLUSIONS: The study elucidated the progression of respiratory hypoxia during toxic pulmonary edema and confirmed that respiratory hypoxia serves as a key pathogenic link, leading to significant disruptions in energy metabolism during the progression of pulmonary edema.

In 2022, researchers from China identified a novel form of copper-dependent cell death, termed cuproptosis, which is distinct from all previously known types of cell death. Cuproptosis is initiated by the binding of copper ions to lipoated enzymes within the Krebs cycle, leading to protein aggregation, proteotoxic stress, and, ultimately, cell death. Copper, as an essential trace element, plays a critical role in numerous physiological processes across nearly all cell types. However, intracellular copper overload can cause oxidative stress and disrupt cellular functions, necessitating tight regulation of copper homeostasis. This article provides a comprehensive summary of current knowledge on copper metabolism, copper-related diseases, and the unique characteristics and regulatory mechanisms of cuproptosis. Furthermore, it explores the role of cuproptosis in the pathogenesis of conditions such as Wilson’s disease, Menkes disease, neurodegenerative disorders, cancer, and cardiovascular diseases, alongside its potential as a therapeutic target for pharmacological intervention.

Pyotr Prokofyevich Denisenko (1923–2011) was a distinguished Russian pharmacologist, Doctor of Medical Sciences, Professor, and Honored Scientist of the RSFSR. A veteran of the Great Patriotic War (1941–1945), he was awarded with 11 military honors. For 26 years (1963–1989), he served as the head of the Department of Pharmacology at the Sanitary and Hygienic State Medical Institute of the Ministry of Health of the RSFSR. He is widely recognized for his pioneering research on synaptic transmission pharmacology and the cholinergic mechanisms regulating bodily functions. Denisenko authored groundbreaking studies and monographs, including Gangliolytics (1959), Central Cholinolytics (1965), and The Role of Cholinoreactive Systems in Regulatory Processes (1980). He mentored a generation of Russian pharmacologists, supervising 28 doctoral and 127 candidate dissertations. Denisenko played a direct role in the development of numerous pharmaceuticals, including ganglioblockers (benzhexonium), central cholinolytics (metamizil), anxiolytics (tarden), anti-ischemic agents (etmaben), antiviral drugs (mixovirin), anti-shock agents (mizidol), burn and wound healing treatments (bathizin, santoparin), hepatoprotectors (geranol, polyen, sinabet), peptic ulcer treatments (benzhexonium, labaznik, polyen), antihypoxants (isothiormin), antioxidants (violuric acid), and disinfectants (aquabor). Additionally, he provided the first detailed pharmacological characterization of the natural product mumiyo.

BACKGROUND: The kisspeptin system in the brain is crucial for regulating reproductive functions in humans and animals. In contrast to mammals, the brains of Danio rerio express two types of kisspeptins — Kiss1 and Kiss2. The role of these kisspeptins in hormonal regulation in fish remains an important area of investigation.

AIM: To examine the effects of Kiss1 and Kiss2 on corticoliberin and gonadoliberin gene expression in the midbrain and diencephalon of Danio rerio.

MATERIALS AND METHODS: Kisspeptins Kiss1 and Kiss2 are oligopeptides consisting of 13 and 9 amino acid residues, respectively. Danio rerio fish were administered intracerebroventricular injections of 1 ng and 4 ng of each peptide at 1 μL volumes. At 1 and 4 hours post-administration, the fish brains were extracted, and the midbrain and diencephalon were isolated as a single complex. Gene expression levels of corticoliberin and gonadoliberin were analyzed using real-time polymerase chain reaction (PCR).

RESULTS: Intracerebroventricular administration of Kiss1 and Kiss2 significantly modulated corticoliberin and gonadoliberin gene expression in the midbrain and diencephalon of Danio rerio. In the group injected with 4 ng of Kiss1, corticoliberin gene expression increased 17- and 65-fold after 4 hours compared to the control groups. In the group administered 1 ng of Kiss2, corticoliberin gene expression increased by 23- and 92-fold compared to the control groups after 1 hour. In the group administered 4 ng of Kiss1, gonadoliberin gene expression decreased threefold compared to the control group euthanized at 1 hour. In the group administered 1 ng of Kiss2, gonadoliberin gene expression decreased fourfold compared to the control group after 1 hour. In the group administered 1 ng of Kiss2, gonadoliberin gene expression decreased threefold compared to the control group after 4 hours.

CONCLUSION: The experimental results reveal that Kiss1 and Kiss2 kisspeptins in Danio rerio stimulate corticoliberin gene expression while suppressing gonadoliberin gene expression in the midbrain and diencephalon.