Background and hypothesis: The high sensitivity of hematopoietic cells, especially stem cells, to radiation and to pro-oxidative and other leukemogenic agents is related to certain of their morphological and metabolic features. It is attributable to the low (minimal) number of active mitochondria and the consequently slow utilization of O₂ entering the cell. This results in an increased intracellular partial pressure of O₂ (pO₂) and increased levels of reactive oxygen (ROS) and nitrogen (RNS) species, and a Δ(PO – AO) imbalance between the pro-oxidative (PO) and antioxidative (AO) constituents. Proposed mechanism: Because excessive O₂ is toxic, we suggest that hematopoietic cells exist in a kind of unstable dynamic balance. This suggestion is based on the idea that mitochondria not only consume O₂ in the process of ATP production but also constitute the main anti-oxygenic stage in the cell's protective antioxidative system. Variations in the mitochondrial base capacity (quantity and quality of mitochondria) constitute an important and highly efficient channel for regulating the oxidative stress level within a cell. The primary target for leukemogenic agents is the few mitochondria within the hematopoietic stem cell. Disturbance and weakening of their respiratory function further enhances the initial pro-oxidative state of the cell. This readily results in peroxygenation stress, creating the necessary condition for inducing leukemogenesis. We propose that this is the main cause of all related genetic and other disorders in the cell. ROS, RNS and peroxides act as signal molecules affecting redox-sensitive transcription factors, enzymes, oncogenes and other effectors. Thereby, they influence the expression and suppression of many genes, as well as the course and direction of proliferation, differentiation, leukemogenesis and apoptosis. Differentiation of leukemic cells is blocked at the precursor stage. While the transformation of non-hematopoietic cells into tumor cells starts during proliferation, hematopoietic cells become leukemic at one of the interim stages in differentiation, and differentiation does not continue beyond that point. Proliferation is switched to differentiation and back according to a trigger principle, again involving ROS and RNS. When the leukemogenic Δ_L(PO – AO) imbalance decreases in an under-differentiated leukemia cell to the differentiation level Δ_D(PO – AO), the cell may continue to differentiate to the terminal stage. Conclusion: The argument described in this article is used to explain the causes of congenital and children's leukemia, and the induction of leukemia by certain agents (vitamin K3, benzene, etc.). Specific research is required to validate the proposals made in this article. This will require accurate and accessible methods for measuring and assessing oxidative stress in different types of cells in general, and in hematopoietic cells in particular, in their different functional states.

Background: The use of natural hepatoprotective remedies represents an important path in modern phytotherapy. Objectives: In this context, our research aims to evaluate the phytochemical composition and the hepatoprotective and oxidative stress reduction potential of an Arctium tomentosum Mill. root extract. Methods: The phenolic profile of the tested extract, prepared by the subcritical fluid-assisted method were qualitatively and quantitatively analyzed by spectrophotometrical and HPLC/DAD/ESI methods. In vitro antioxidant capacity was assessed using DPPH and FRAP assays. Hepatoprotective activity of the extract was assessed on a model of CCl₄ experimentally induced hepatotoxicity in mice. Results: Phytochemical assays revealed the presence of important polyphenols, such as chlorogenic acid (17.20 ± 0.65 μg/mL) and acacetin 7-O-glucoside (56.80 ± 1.66 μg/mL). In vitro, the tested extract exhibited a significant oxidative stress reduction capacity, while in vivo it showed a dose-dependent hepatoprotective effect indicated by an improvement in plasma proteins profile and down-regulation of plasma transaminase activity (ALAT, ASAT, GGT). In liver tissue, the extract partially restored the activity of GPx, CAT, and SOD and attenuated lipid peroxidation. The protective effect of the A. tomentosum root extract was supported by the alleviation of histological injuries of the liver (centrilobular necrosis, granulocytic infiltrate, and fibrosis). Conclusions: The A. tomentosum subcritical fluid-assisted root extract proved to be able to provide a significant hepatoprotective effect mainly through an antioxidant mechanism.

Background/Objectives: Our work was designed to study the physicochemical properties, safety profile, pharmacokinetics, and prophylactic efficacy of an original iodine–dextrin-based pharmaceutical formulation (PA), both alone and in combination with azithromycin (AZ), in a murine model of LPS-induced sepsis. Methods/Results: UV–vis and ¹H-NMR spectroscopy confirmed the formation of a stable iodine–dextrin complex, with triiodide anions stabilized by hydrogen bonding and donor–acceptor interactions. No clinical signs of acute toxicity were observed at doses up to 5000 mg/kg, and subacute administration (62.5 and 125 mg/kg) showed no adverse effects on hematological or biochemical parameters. A mild, non-pathological enlargement of thyrocytes and parallel increases in TSH, T3, and T4 levels were observed at 125 mg/kg, consistent with physiological adaptation to iodine. Pharmacokinetic analysis revealed high oral bioavailability (~92%), prolonged half-life (~21 h), and wide tissue distribution with low clearance. In the sepsis model, pretreatment with AZ+PA alleviated clinical symptoms, maintained body weight, and significantly improved hematological parameters, reducing WBCs and CRP levels. The combination also decreased plasma IL-6 and TNF-α concentrations more effectively than either agent alone, indicating a synergistic anti-inflammatory effect. Histological analysis confirmed that PA, particularly in combination with AZ, mitigated LPS-induced tissue injury in the liver, kidney, and lungs. Conclusions: These findings suggest that PA is a safe, bioavailable compound with immunomodulatory properties that enhance azithromycin’s protective effects during systemic inflammation. This supports its potential use as a prophylactic agent in clinical settings, such as preoperative immune modulation to prevent sepsis-related complications.