ABSTRACT
Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent.
Subject(s)
Acute Lung Injury/chemically induced , Alkylating Agents/toxicity , Chemical Warfare Agents/toxicity , Disease Models, Animal , Lung/drug effects , Mustard Gas/toxicity , Respiratory Mucosa/drug effects , Acute Lung Injury/immunology , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/immunology , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/ultrastructure , Animals , Apoptosis/drug effects , Biomarkers/metabolism , Bronchoalveolar Lavage Fluid/chemistry , DNA Damage , Endoplasmic Reticulum, Rough/drug effects , Endoplasmic Reticulum, Rough/immunology , Endoplasmic Reticulum, Rough/metabolism , Endoplasmic Reticulum, Rough/ultrastructure , Lung/immunology , Lung/metabolism , Lung/ultrastructure , Lymphocyte Activation/drug effects , Male , Microscopy, Electron, Transmission , Microvilli/drug effects , Microvilli/immunology , Microvilli/metabolism , Microvilli/ultrastructure , Mitochondria/drug effects , Mitochondria/immunology , Mitochondria/metabolism , Mitochondria/ultrastructure , Oxidative Stress/drug effects , Rats, Sprague-Dawley , Respiratory Mucosa/immunology , Respiratory Mucosa/metabolism , Respiratory Mucosa/ultrastructure , Specific Pathogen-Free OrganismsABSTRACT
Objective: To observe effects of Yuzhang Decoction on in vitro proliferation of bone marrow CD_(34) cells in the patient of aplastic anemia (CAA) and its mechanism. Methods: To adopt monoclone antibody-immune magnetic beads separation system (MACS) to separate and purify CD_(34) cells in bone marrow of the patient of CAA, and make cell culture, applying ~3H-TdR incorporation to detect effect of Yuzhang Decoction on proliferation of CD_(34) cells of bone marrow. Results: CD_(34) cells of bone marrow showed concentration-dependent proliferation in the Yuzhang Decoction group with significantly differences (P
