Ferroptosis is a type of regulated cell death driven by iron-dependent lipid peroxidation that has received extensive attention in recent years. A growing body of evidence suggests that ferroptosis contributes to the progression of drug-induced liver injury. Therefore, the role and mechanism of ferroptosis in the process of drug-induced liver injury deserve further extensive and in-depth exploration, which will aid in the discovery of novel biomarkers as well as the identification of potential approches of targeting ferroptosis to intervene in drug-induced liver injury.
Humans ; Biomarkers/metabolism* ; Chemical and Drug Induced Liver Injury ; Ferroptosis ; Iron/metabolism* ; Lipid Peroxidation/physiology*

ObjectiveTo investigate the effects of resveratrol in the cryopreservation medium on the quality and function of post-thaw sperm.

METHODSSemen samples were obtained from 50 normozoospermic and 50 oligoasthenozoospermic men, liquefied and then cryopreserved in the glycerol-egg yolk-citrate (GEYC) medium with or without 30 μmol/L resveratrol. Sperm motility, viability and acrosome reaction (AR) were examined before and after thawing. Sperm lipid peroxidation and the level of reactive oxygen species (ROS) were measured using commercial malondialdehyde (MDA) and the ROS assay kit. Sperm mitochondrial membrane potential (MMP) and DNA damage were determined by Rhodamine 123 staining and TUNEL.

RESULTSThe percentage of progressively motile sperm (PMS), total sperm motility, sperm viability, MMP and AR were significantly decreased (P <0.05) while the levels of sperm ROS, MDA and DNA fragmentation index (DFI) remarkably increased in both the normozoospermia and oligoasthenozoospermia groups after cryopreservation as compared with those in the fresh ejaculate (P <0.05). In comparison with the non-resveratrol control, the post-thaw sperm cryopreserved with 30 μmol/L resveratrol showed markedly higher PMS (［32.7 ± 4.8］ vs ［43.1 ± 6.3］ %, P <0.05), total motility (［44.8 ± 6.9］ vs ［56.9 ± 7.4］ %, P <0.05), viability (［52.3 ± 6.1］ vs ［67.5 ± 5.6］ %, P <0.05), MMP (［56.5 ± 7.0］ vs ［63.4 ± 7.5］ %, P <0.05) and AR (［16.6 ± 3.8］ vs ［26.3 ± 4.7］ %, P <0.05) but lower ROS, MDA and DFI (all P <0.05) in the normozoospermia group, and so did the post-thaw sperm in the oligoasthenozoospermia group, with a particularly lower DFI (［28.5 ± 4.8］ vs ［36.3 ± 5.7］%, P <0.01).

CONCLUSIONSResveratrol in the cryopreservation medium can improve the quality and function of post-thaw human sperm by reducing cryopreservation-induced sperm injury and the level of ROS.

Acrosome ; drug effects ; Animals ; Antioxidants ; pharmacology ; Cryopreservation ; methods ; DNA Fragmentation ; Humans ; Lipid Peroxidation ; Male ; Malondialdehyde ; Membrane Potential, Mitochondrial ; Reactive Oxygen Species ; analysis ; Resveratrol ; pharmacology ; Semen Analysis ; Semen Preservation ; adverse effects ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; physiology

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.
Animals ; Diabetes Mellitus/enzymology/*metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Genotype ; Hippocampus/*enzymology/metabolism ; Lipid Peroxidation/*physiology ; Male ; Malondialdehyde/metabolism ; Physical Conditioning, Animal/*physiology ; Rats ; Rats, Zucker ; Superoxide Dismutase/genetics/*metabolism

The study focused on the therapeutic efficacy of Tibetan medicines on cerebral ischemia. The combined medication methods and administration habits in clinic for more than 10 years were simulated. Three typical Tibetan medicines, i.e., 25-Herb Shanhu pill, Wishful-Treasure pill and 20-Herb Chenxiang pill, were administered to the animal model of permanent middle cerebral artery occlusion in the morning, noon and evening, respectively. On the second day after the final administration, the activity of serum oxidative stress marker SOD and the content of MDA were evaluated. Infarct volumes were quantified through TTC staining. Inflammatory reaction maker NF-kappaB p65 gene and apoptosis. makers Bax and Cyct were selected to study the molecular mechanism of combined herbs with the immunohistochemistry technique. According to the result, the respective combination of 25-Herb Shanhu pill, Wishful-Treasure pill and 20-Herb Chenxiang pill in the morning, noon and evening showed unique advantages in reducing the damage of oxidative stress, infarct volumes, encephaledema caused by ischemia, inflammatory factor aggregation and inhibiting apoptosis, with consistent therapeutic efficacies in clinic.
Animals ; Brain Ischemia ; drug therapy ; metabolism ; Lipid Peroxidation ; Male ; Medicine, Tibetan Traditional ; Rats ; Superoxide Dismutase ; metabolism ; Time Factors ; Transcription Factor RelA ; physiology

OBJECTIVETo investigate the effect of hydrogen sulfide (H2S) on mitochondrial function in acute myocardial ischemia in rats.

METHODSAcute myocardial ischemia models were established by ligating the left anterior descending coronary artery (LADC) of rats. Fourty-eight male SD rats were randomly divided into 6 groups (n = 8): sham operation group, ischemia group, ischemia + sodium hydrosulfide (NaHS) low, middle and high dose groups and ischemia + DL-proparglycine(PPG) group. The ultrastructures of myocardial mitochondria were observed with electron microscope. The content of H2S in plasma and the activity of cystathionine-gamma-lyase (CSE) in myocardial tissue of rats were respectively detected. The swelling and activity of myocardial mitochondria were determined. The activities of ATPase, GSH-Px, SOD and the content of malondial-dehyde (MDA) in myocardial mitochondria of rats were also measured.

RESULTSCompared with those of the sham operation group, the content of H2S in plasma, the activity of CSE in myocardial tissue and the activity of myocardium mitochondria were significantly decreased. The activities of ATPase, SOD, GSH-Px in myocardial mitochondria were significantly decreased, The content of malondial dehyde(MDA) in myocardial mitochondria and the swelling of mitochondria were distinctly increased in the ischemia group (P < 0.01). Compared with those of the ischemia group, the content of H2S in plasma and the activity of CSE in myocardial tissue were increased, and the activities of mitochondria, ATPase, SOD, and GSH-Px in myocardial mitochondria were significantly increased in ischemia + NaHS low, middle and high-dose groups; the swelling of mitochondria and the content of MDA in myocardial mitochondria were significantly decreased in ischemia + NaHS middle and high-dose groups (P < 0.05 or P < 0.01). The administration of PPG could partially reduce the myocardial protection of hydrogen sulfide (P < 0.05 or P < 0.01).

CONCLUSIONIt could be concluded that the administration of hydrogen sulfide could enhance the activities of mitochondrial ATPase, SOD, GSH-Px, decrease the level of mitochondrial lipid peroxidation, and play a protective effect against acute myocardial ischemia.

Adenosine Triphosphatases ; metabolism ; Animals ; Glutathione Peroxidase ; metabolism ; Hydrogen Sulfide ; pharmacology ; Lipid Peroxidation ; drug effects ; Male ; Mitochondria, Heart ; drug effects ; metabolism ; physiology ; Myocardial Ischemia ; physiopathology ; prevention & control ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate oxidative stress, hemoglobin percentage and erythrocyte osmotic fragility in various aging groups.

METHODSA total of 200 healthy volunteers of both genders between age group 20-65 years were selected by random method. Determination of hemoglobin percentage was done employing modified cyanide method of Dacie and Lewis. The erythrocyte lysis was observed in hypotonic solution of buffered saline at varying concentrations and optical density was measured at 540 nm. The extent of lipid peroxidation in form of malondialdehyde was measured by thiobarbituric acid method.

RESULTSThe study found a significant decrease in hemoglobin percentage, increase in erythrocyte osmotic fragility and increased lipid peroxidation in form of malondialdehyde with increasing age.

CONCLUSIONSSupplementation of antioxidants may prevent the oxidative injury in elderly group of subjects.

Adult ; Aged ; Aging ; physiology ; Erythrocytes ; chemistry ; Female ; Hemoglobins ; analysis ; Humans ; Lipid Peroxidation ; physiology ; Male ; Malondialdehyde ; analysis ; metabolism ; Middle Aged ; Osmotic Fragility ; Oxidative Stress ; Young Adult

OBJECTIVETo evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin.

METHODSRats were exposed to warfarin by applying 10 μg of warfarin-sodium to 10-12 cm(2) skin (range 0.8-1 μg per 1 cm(2)) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application.

RESULTSRepeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo-morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA(+)) cells indicated reparative processes in injured skin. Infiltration of CD3(+) cells (T lymphocytes) along with the increased production of tumor necrosis factor-a (TNF-a) by epidermal cells from warfarin-treated skin and their co-stimulatory effect in an in vitro T-cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin.

CONCLUSIONPresented data have documented tissue damage associated with immune/inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.

Animals ; CD3 Complex ; genetics ; metabolism ; Dermatitis, Contact ; pathology ; Epidermis ; cytology ; Gene Expression Regulation ; physiology ; Inflammation ; metabolism ; Lipid Peroxidation ; Male ; Proliferating Cell Nuclear Antigen ; genetics ; metabolism ; Rats ; Rodenticides ; pharmacology ; Skin ; cytology ; drug effects ; metabolism ; T-Lymphocytes ; physiology ; Warfarin ; pharmacology

OBJECTIVETo explore the protective effects of ischemic preconditioning (IPC) on the lung injury following with limbs ischemia /reperfusion (LI/R).

METHODSThe models of LI/R injury were constructed in rabbits. The blood from right external jugular vein and left common carotid artery, into and out-flowing pulmonary blood (IPB, OPB) respectively. Superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) in IPB and OPB and lung tissues were measured, as well as total nitric oxide synthase (tNOS) and inducible nitric oxide synthase (iNOS) in lung tissues were detected in different groups. The effects of IPC on the lung injury were observed.

RESULTSCompared with sham and before ischemic, the activity of SOD decreased and the content of MDA and NO increased after 4 h ischemia followed by 4 h reperfusion in IPB, OPB and lung tissues. The activity of tNOS and iNOS in lung tissues increased remarkably as well, there was statistical significance (P < 0.05, P < 0.01). SOD increased and MDA, NO, tNOS, iNOS decreased significantly by IPC before ischemia/reperfusion. The correlation analysis indicated that MDA was negatively correlated with SOD and was positively correlated with MDA, NO, iNOS (P < 0.01).

CONCLUSIONOxygen free radicals metabolic confusion of lung occurred in the course of LI/R, IPC could strengthen the resistance of peroxidation in lung and had protective effects on the lung injury following with LI/R.

Animals ; Extremities ; blood supply ; Female ; Ischemic Preconditioning ; methods ; Lipid Peroxidation ; physiology ; Lung Injury ; metabolism ; physiopathology ; prevention & control ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rabbits ; Reperfusion Injury ; physiopathology ; Superoxide Dismutase ; metabolism

INTRODUCTIONHaemoglobin (Hb) E beta-thalassaemia is a common thalassaemic disorder in Southeast Asia and is very common in the eastern and north-eastern parts of India. The disease cause rapid erythrocyte destruction due to the free radical mediated injury but factors for the oxidative injury are not clearly known. We investigated the free reactive iron (non-haem) mediated insult in Hb E beta-thalassaemia.

MATERIALS AND METHODSThirty Hb E beta-thalassaemic patients (age range, 3 to 15 years) who had undergone blood transfusion at least 1 month prior to sampling and 32 normal healthy individuals (age range, 18 to 30 years) were included in this study. We estimated the ferrozine detected intracellular erythrocytic free reactive iron (nonhaem iron), reduced glutathione (GSH), glutathione reductase activity, cellular damage marker serum thiobarbituric acid reacting substances (TBARS) and also serum ferritin using standard methods.

RESULTSWe found that the erythrocytic free reactive iron was significantly higher (P <0.001) in Hb E beta patients and was about 30% more than in controls. The elevated level of erythrocytic non-haem iron was associated with a high level of serum TBARS which was about 86% higher in patients than in controls. The serum ferritin level was also significantly higher (P <0.001) compared to controls. The erythrocytic reduced glutathione level was significantly lower (P <0.001) at about 65% less in the patients' group and the erythrocytic glutathione reductase enzyme was also found to be significantly lower (P <0.001) in Hb E beta-thalassaemia.

CONCLUSIONSWe concluded that a significantly elevated level of erythrocytic free reactive iron and lipid peroxidation end product was associated with low erythrocytic GSH level. This reflects non-haem iron mediated cellular damage in Hb E beta-thalassaemia.

Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Erythrocytes ; metabolism ; Ferritins ; blood ; Glutathione ; blood ; Glutathione Reductase ; blood ; Hemoglobin E ; Humans ; Iron ; blood ; Lipid Peroxidation ; Oxidative Stress ; physiology ; Thiobarbituric Acid Reactive Substances ; metabolism ; beta-Thalassemia ; blood ; physiopathology

OBJECTIVETo study the effect of light intensity on physiological and biochemical characteristics of Chrysanthemum morifolium at the vegetative stage.

METHODThe dynamic response of physiological and biochemical indexes of Ch. morifolium were measured under different treatments (100%, 80%, 60%, 40% and 20% of the full sunlight) at the vegetative stage.

RESULTThe physiological and biochemical indexes of Ch. morifolium showed dynamic changes with the progress of growth and the increase of the treatment time. The soluble sugar content decreased when the light intensity reduced, and had a significant positive correlation with the light intensity. Soluble protein content rose firstly and fell later, malondialdehyde content increased, superoxide dismutase and catalase activity decreased initially and increased afterwards.

CONCLUSIONProper shading benefits the nitrogen accumulation of Ch. morifolium at the vegetative stage, and reduces the strength of stress condition. The suitable light environment for growth of Ch. morifolium at the vegetative stage is about 80%-60% of full sunlight and the optimum treatment time is 20-40 days.

Catalase ; metabolism ; Chrysanthemum ; physiology ; Light ; Lipid Peroxidation ; Superoxide Dismutase ; metabolism