There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.
Acute Radiation Syndrome ; blood ; immunology ; prevention & control ; Animals ; Blood Cells ; drug effects ; radiation effects ; Dose-Response Relationship, Drug ; Gamma Rays ; adverse effects ; Hydroxamic Acids ; therapeutic use ; Indoles ; therapeutic use ; Matrix Metalloproteinase Inhibitors ; therapeutic use ; Mice ; Radiation Injuries, Experimental ; blood ; immunology ; prevention & control ; Radiation-Protective Agents ; therapeutic use ; Spleen ; drug effects ; immunology ; radiation effects ; Survival Analysis ; Whole-Body Irradiation

OBJECTIVETo study the protective effect of baicalin solid dispersion (BSD) on D-galactosamine (D-GalN) induced acute hepatic injury in mice, and to compare it with baicalin alone.

METHODSSixty mice were randomly divided into six groups, i.e., the normal control group, the D-GalN model group, the bifendate group (at the daily dose of 200 mg/kg), the baicalin group (at the daily dose of 50 mg/kg), the low dose BSD group (at the daily dose of 50 mg/kg), and the high dose BSD group (at the daily dose of 100 mg/kg), 10 in each group. 0.5% CMC-Na at 20 mL/kg was administered to mice in the normal group and the model group by gastrogavage, while corresponding medication was administered to mice in the other three groups by gastrogavage. Seven days after administration, acute hepatic injury model was induced by intraperitoneal injection of D-GalN. The liver index and the spleen index were calculated. The serum activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST), the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver homogenate were measured. The pathological changes of the liver tissue were observed by HE staining.

RESULTSCompared with the normal control group, widespread inflammation and necrosis was significant in the liver tissue of the D-GalN model group; the liver index, serum ALT and AST levels and hepatic MDA content obviously increased, hepatic SOD activity decreased, showing statistical difference (P < 0.05). Compared with the model group, the liver index, the serum levels of ALT and AST, and hepatic MDA decreased, hepatic SOD increased, the degree of hepatic tissue injury was significantly improved in the low dose and high dose BSD groups. Besides, better effects were obtained in the low dose BSD group than in the baicalin group with statistical difference (P < 0.05).

CONCLUSIONBSD could significantly protect D-GalN induced acute hepatic injury of mice, and its effect was superior to that of baicalin alone.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; blood ; drug therapy ; Flavonoids ; therapeutic use ; Galactosamine ; adverse effects ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred Strains ; Protective Agents ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the therapeutic efficacy of Dangfei Liganning Tablet (DLT) in the treatment of antipsychotics induced mild hepatic damage.

METHODSTotally 80 mental inpatients with antipsychotics induced mild liver injury were randomly assigned to two groups, the treatment group (40 cases) and the control group (40 cases). Patients in the treatment group took DLT, two tablets each time, three times per day, while those in the control group took Liver-protecting Tablet (LT), four tablets each time, three times per day. The treatment course was 4 weeks for all. Changes of glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) were observed before treatment, week 1, 2, and 4 after treatment. The therapeutic efficacy was compared between the two groups.

RESULTSCompared with the former time point, ALT and AST gradually decreased in the two groups at week 1, 2, and 4 (P <0. 05). The cured rate was 72. 5% and the total effective rate was 97. 5% in the treatment group. They were 62. 5% and 90. 0% respectively in the control group. There was no statistical difference in the two indices between the two group (P >0.05). No obvious adverse reaction occurred in the two groups.

CONCLUSIONDLT could treat antipsychotics induced mild hepatic damage in a safe and effective way.

Alanine Transaminase ; metabolism ; Antipsychotic Agents ; adverse effects ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Humans ; Liver ; metabolism ; Protective Agents ; administration & dosage ; therapeutic use ; Tablets ; therapeutic use

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.
Animals ; Antithyroid Agents/*adverse effects/chemistry/therapeutic use ; Disease Models, Animal ; Drug-Induced Liver Injury/drug therapy/*etiology ; Graves Disease/drug therapy ; Humans ; Hyperthyroidism/drug therapy ; Protective Agents/therapeutic use ; Reactive Oxygen Species/metabolism ; Risk Factors

PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult ; Aged ; Androstanols/adverse effects/pharmacology ; Anesthetics/adverse effects/pharmacology ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Blood Pressure/drug effects ; Etomidate/adverse effects/pharmacology ; Female ; Heart/*drug effects ; Heart Rate/drug effects ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/pharmacology ; Male ; Middle Aged ; Piperidines/adverse effects/*therapeutic use ; Protective Agents/adverse effects/*therapeutic use

OBJECTIVETo observe the expression of P-selectin (Ps), intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-kappa B (NF-kappaB) in lung tissues of acute lung injury (ALI) rat model induced by oleic acid (OA) and to explore the protective effects of melatonin (MT) in lung tissues in rats.

METHODSAll rats were randomly divided into four groups: control group, OA group, MT + OA group and SB203580 + OA group. Rat model of ALI was established by intravenous injection of oleic acid (OA). Lung coefficient was measured, lung tissues were imbedded by paraffin to observe morphological changes and the expression of Ps, ICAM-1 and NF-kappaB in lung tissues by means of immunohistochemistry staining.

RESULTSCompared with control group, the lung coefficient increased significantly in OA group (P < 0.05). Alveolar septum thickened significantly in OA group, there had many infiltrated inflammatory cells and collapsed alveoli of lung; positive expression of Ps, ICAM-1 and NF-kappaB were very obvious (P < 0.05); the administration of MT and SB203580 mitigated above changes significantly (P < 0.05).

CONCLUSIONMT possesses obviously protective effect on lung tissues during ALI, its protective mechanism might be related to the inhibition of the expression of Ps, ICAM-1 and NF-kappaB.

Acute Lung Injury ; chemically induced ; physiopathology ; prevention & control ; Animals ; Down-Regulation ; drug effects ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Melatonin ; pharmacology ; therapeutic use ; NF-kappa B ; metabolism ; Oleic Acid ; adverse effects ; P-Selectin ; metabolism ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the protective effects of sodium aescinate (SA) preconditioning on the tourniquet-induced ischemia-reperfusion (I/R) injury after limbs operation.

METHODSSeventy-five patients with grade I-II issued by American Society of Anesthesiology undergoing lower limb operation were randomly assigned to 3 groups: the control group, low-dose SA-treated group and high-dose SA-treated group; each group enrolled 25 patients. The patients were treated with 5 mg and 10 mg SA 30 min before tourniquet inflation in the two treatment groups separately, while the patients in the control group received normal saline. Venous blood samples were obtained before tourniquet was inflated (T0 baseline). And 5 (T1), 10 (T2), 20 (T3) min after tourniquet was released. The nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined by commercial kits. Meanwhile, arterial pressure (MAP) and heart rate (HR) were monitored from an automatic invigilator.

RESULTSIn the control group, MDA and NO levels were increased, and SOD and MAP were decreased significantly after tourniquet deflation compared to T0 baseline (P<0.05). After tourniquet deflation, MDA and NO levels in the two treated groups were significantly decreased; meanwhile, SOD levels and MAP were increased, and the variations of HR were more stable compared with the control group (all P<0.05). There was no significant difference in all of the above between the two treated groups (P>0.05).

CONCLUSIONThe protective effects of SA preconditioning on tourniquet-induced limb I/R injury might possibly contribute to the increasing of SOD levels, and MAP and the decreasing of MDA and NO levels.

Adult ; Dose-Response Relationship, Drug ; Female ; Hemodynamics ; drug effects ; Humans ; Ischemic Preconditioning ; Leg ; blood supply ; pathology ; Male ; Middle Aged ; Protective Agents ; adverse effects ; pharmacology ; therapeutic use ; Reperfusion Injury ; blood ; drug therapy ; physiopathology ; Sodium ; adverse effects ; pharmacology ; therapeutic use ; Tourniquets ; Vital Signs ; drug effects ; Young Adult

Acute Disease ; Adult ; Chemical and Drug Induced Liver Injury ; diagnosis ; drug therapy ; etiology ; pathology ; Drugs, Chinese Herbal ; adverse effects ; isolation & purification ; Female ; Gastritis ; etiology ; Humans ; Liver ; pathology ; Liver Function Tests ; Male ; Middle Aged ; Olea ; chemistry ; Plant Bark ; chemistry ; Protective Agents ; therapeutic use ; Retrospective Studies

Amifostine ; therapeutic use ; Animals ; Head and Neck Neoplasms ; radiotherapy ; Humans ; Oral Health ; Radiation Injuries ; etiology ; prevention & control ; therapy ; Radiation-Protective Agents ; therapeutic use ; Radiotherapy ; adverse effects ; Radiotherapy, Conformal ; Salivary Glands ; radiation effects ; Salivation ; radiation effects ; Submandibular Gland ; surgery ; transplantation ; Xerostomia ; etiology ; prevention & control ; therapy

Radiation-induced lung injury (RILI) is the most common complication of the radiotherapy for thoracic tumor. It can lower the ratio of local control and seriously affect the patients' quality of life. At present, the clinical management of RILI is not more than the use of glucocorticoid and anti-inflammatory agent for symptomatic treatments. These treatments do not have any preventive effect but cause much side reactions. In this paper, we review the data from the contigency researches on the mechanism of RILI, from the researches on gene therapy and stem cell-therapy, and we dicuss the more safe, more stable and more efficacious treatment of RILI.
Antioxidants ; therapeutic use ; Genetic Therapy ; methods ; Humans ; Lung ; pathology ; radiation effects ; Lung Neoplasms ; radiotherapy ; Mesenchymal Stem Cell Transplantation ; methods ; Radiation Injuries ; etiology ; therapy ; Radiation Pneumonitis ; etiology ; therapy ; Radiation-Protective Agents ; therapeutic use ; Radiotherapy, Conformal ; adverse effects