Radioprotective effect of geraniin via the inhibition of apoptosis triggered by γ-radiation-induced oxidative stress

The radioprotective effect of geraniin, a tannin compound isolated from Nymphaea tetragona Georgi var. (Nymphaeaceae), against γ-radiation-induced damage was investigated in Chinese hamster lung fibroblast (V79-4) cells. Geraniin recovered cell viability detected by MTT test and colony formation assay, which was compromised by γ-radiation, and reduced the γ-radiation-induced apoptosis by the inhibition of loss of the mitochondrial membrane potential. Geraniin protected cellular components (lipid membrane, cellular protein, and DNA) damaged by γ-radiation, which was detected by lipid peroxidation, protein carbonyl formation, and comet assay. Geraniin significantly reduced the level of intracellular reactive oxygen species generated by γ-radiation, which was detected using spectrofluorometer, flow cytometer, and confocal microscope after 2′,7′-dichlorodihydrofluorescein diacetate staining. Geraniin normalized the superoxide dismutase and catalase activities, which were decreased by γ-radiation. These results suggest that geraniin protects cells against radiation-induced oxidative stress via enhancing of antioxidant enzyme activities and attenuating of cellular damage.     

The preventive effect of Se-methylselenocysteine on γ-radiation-induced oxidative stress in rat lungs

We investigated the preventive effect of Se-methylselenocysteine (MSC) administration on γ-radiation (whole body irradiation, single 10-Gy dose)-induced oxidative damage in rat lungs. Rats were pretreated with MSC (0.75 mg/rat/day) for 1 week before γ-irradiation. The MSC pretreatment prevented the irradiation-induced increase in lipid peroxidation and the concomitant decrease in cellular glutathione content. The prevention of irradiation-induced oxidative damage in MSC-pretreated rat lungs appeared to be associated with increased antioxidant capacity, particularly in the glutathione system. The 1-week MSC treatment resulted in an increase in glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase activities, which are involved in glutathione redox cycling. An increase in catalase activity was also observed in the rat lungs. Additionally, a significantly increased level of nuclear factor erythroid 2-related factor 2 (Nrf2) was exhibited in the MSC-treated rat lungs. Heme oxygenase 1, glutathione S-transferase pi, and peroxiredoxin 1, which are known target proteins of Nrf2, were also increased in MSC-treated lungs. These results implicate Nrf2 signaling in the MSC-induced activation of the antioxidant system.     

Protective effect of 17β-estradiol on oxidative stress and liver dysfunction in aged male rats

In aging liver oxidative stress increases due to the decrease in antioxidant bio-molecules such as estrogens which can be modified by hormonal replacement therapy (HRT). With this in mind, we hypothesized that age-related decline in steroidogenesis may be associated with the impairment of the antioxidant defense cells in liver, the increase in lipid peroxidation, hepatic dysfunction and histological changes; estrogens prevent all these changes induced by aging. 17beta-estradiol treatment was initiated in 12 month-old Wistar rats, and continued until 18 months of age. Our results showed that 17beta-estradiol (E2) level in the serum of the aged untreated rats was reduced by -32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase (GPX) activities were reduced by -47, -46, and -29% respectively in old rat liver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasma such as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well as bilirubin level increased significantly in old rats, and histological changes were investigated. In E2-treated rats, protective effects were observed. Indeed, 17beta-estradiol attenuates all changes induced by aging. The 17beta-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activities were higher by +28, +15, and +11% respectively. This anti-aging effect of estrogens was clarified by a lower level of lipid peroxidation and liver dysfunction parameters as well as by histological observation.     

Effects of α lipoic acid on noise induced oxidative stress in rats

This study was conducted to identify how exposure to ambient noise that is over 75 dB affects the oxidant-antioxidant profile using hematological and biochemical indicators, and to investigate the effects of a strong and current antioxidant, $\alpha$ lipoic acid, on rats that were subjected to noise stress. For this purpose, five groups of eight rats were formed as follows: Control (K), Noise Exposure (GK), Lipoic Acid (LA), Noise Pollution + $\alpha$Lipoic Acid (GK + LA) and Oil (Y). The blood samples collected from rats were analyzed and MDA (malondialdehyde), GSH (glutathione), SOD (superoxide dismutase), CAT (catalase), NO (nitrit oxide), GPx (glutathione peroxidase), leukocytes, monocytes, lymphocytes, erythrocytes, hemoglobin, hematocrit, glucose, cholesterol, total protein, triglycerides, HDL (high density lipoprotein), LDL (low density lipoprotein), and urea-N levels were measured. The physical factory environment in a textile factory was preferred to simulate the noise exposure. Ambient noise was measured to be 75 dB. Exposure to physical ambient noise was sustained for 30 days. MDA level was measured at the lowest level in the LA and GKLA groups while it was statistically significantly higher in other groups than it was in the control group. It was observed that GSH reached its lowest level in the group that was exposed to noisy environment, the 100 mg/kg/day $\alpha$lipoic acid administered on the experimental model increased this level to that of the control group and this change was statistically significant (p < 0.05). Considering the urea levels, the increases in GK and GKLA groups and the decreases in LA and Y groups were observed to be statistically significant. When glucose levels were compared to the control group, they were found to be statistically significantly lower in all groups. As a result, it was observed that exposure to noise for 30 days was likely to lead to leukocyte-based immune deficiency and using $\alpha$ lipoic acid as an antioxidant might provide a significant protection against the noise stress.     

Protective effect of Salvia miltiorrhiza aqueous extract on myocardium oxidative injury in ischemic–reperfusion rats

Salvia miltiorrhiza has strong antioxidative activity. They may have a strong potential as cardioprotective agents in ischemic–reperfusion injury. Experiments were carried out in Sprague–Dawley rats with myocardium ischemia reperfusion (IR). Myocardial injuries during IR were determined by changes in electrocardiogram analysis of arrhythmias, antioxidant enzyme activities, AST, CK-MB, lactate dehydrogenase (LDH) levels, and myocyte apoptosis. Results showed that S. miltiorrhiza aqueous extract (SAME) pre-treatment significantly decreased the ST-segment (ΣST₁₂₀) and myocardium MDA, AST, CK-MB, lactate dehydrogenase (LDH) levels, increased myocardium antioxidant enzyme activities, and inhibit myocardium cell apoptosis. Furthermore, the SAME pre-treatment significantly upregulated p-JAK2 and p-STAT3 protein expression, decreased myocardium TNF-α and IL-6 concentrations in IR rats. The levels of TNF-α and IL-6 were positively correlated with the changes in myocardium p-JAK2 and p-STAT3 protein expression levels in IR rats. It can be concluded that the SAME pre-treatment has anti-ischemic and anti-apoptosis activity in heart IR rats. SAME pre-treatment protects heart against IR injury, at least in part, through its stimulating effects on injury-induced deactivation of JAK2/STAT3 signaling pathway.     

Blueberry extract attenuates γ-radiation-induced hepatocyte damage by modulating oxidative stress and suppressing NF-κB in male rats

Radiation exposure is known to produce many harmful effects in biological systems, and these effects are often mediated by oxygen free radicals. Because blueberries are rich in antioxidant compounds such as anthocyanins and phenolic acids, we divided forty adult rats into four treatment groups of 10 (G1–4) as follows: G1 rats were used as a control, G2 rats were irradiated with 8?Gy at 2?Gy/week at a dose rate of 0.5?Gy/min, G3 rats were administered blueberry extract (200?mg/kg) and G4 rats were administered blueberry extract during the same irradiation period. In subsequent determinations, γ-irradiated rats had increased levels of cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL), and significantly elevated liver enzyme activities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and total bilirubin. In contrast, significant reductions in albumin, total protein and globulin were observed, whereas gamma irradiation decreased activities of the antioxidant enzymes glutathione (GSH), catalase (CAT), xanthine dehydrogenase (XDH) and superoxide dismutase (SOD). We also observed incremental increases in DNA fragmentation percentages and histopathological changes in liver tissues. Serum pro-inflammatory cytokine levels (IL-6, IL-10 and TNF-α) were significantly elevated and hepatic NF-кB was upregulated. In G4 rats, treatments with blueberry extract restored liver pro-oxidant status, reduced cytokine levels, ameliorated histopathological parameters and reduced DNA damage. In conclusion, γ-radiation exerts toxic effects in the rat livers, and blueberry extract is protective against these.     

Ameliorative effect of 20-OH ecdysone on streptozotocin induced oxidative stress and β-cell damage in experimental hyperglycemic rats

The present study was to evaluate the effects of 20-OH ecdysone on hyperglycemia mediated oxidative stress in streptozotocin induced diabetic rats. Diabetes was induced in experimental rats by single intraperitoneal injection of STZ (45 mg/kg b.w.) dissolved in 0.1 mol/L citrate buffer (pH 4.5). Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of non-enzymic antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic rats. Moreover, hepatic markers (aspartate aminotransferase and alanine aminotransferase) and renal markers (urea, creatinine) were significantly increased in diabetic rats as compared to control rats. Upon treatment with 20-OH ecdysone to diabetic rats showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that 20-OH ecdysone exerts a protective action on pancreatic beta cell function and overcomes oxidative stress through its hypoglycemic potential. The effect produced by the 20-OH ecdysone on various parameters was comparable to that of glibenclamide – an antidiabetic drug.     

Protective effect of β-casomorphin-7 on cardiomyopathy of streptozotocin-induced diabetic rats via inhibition of hyperglycemia and oxidative stress

β-Casomorphin-7 (β-CM-7) is regarded as the most representative milk-derived bioactive peptide. The present work studies the efficacy of β-CM-7 against myocardial injury in streptozotocin-induced diabetic rats, focusing on the following assays: (1) the level of blood glucose and advanced glycosylation end product (AGE), the activity of lactate dehydrogenase (LDH) in serum; (2) the level of hydrogen peroxide (H₂O₂), the activity of Na⁺K⁺-ATPase, Ca²⁺Mg²⁺-ATPase and enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) in myocardial tissue; (3) the protein expression of glucose transporter-4 (GLUT-4) in myocardial tissue. It showed that with the influence of β-CM-7, the levels of blood glucose of β-CM-7 treatment group decreased markedly compared with model group (P < 0.01) accompanied with their alleviated symptoms of diabetes. In the antioxidant and oxidant levels, β-CM-7 treatment group signified a remarkable increase in the activity of GSH-Px, SOD and CAT of the anti-oxidation system and meanwhile demonstrated a considerable reduction in H₂O₂ content (all P < 0.05) in comparison with model group. We also found both the content of AGE and the activity of LDH of β-CM-7 treated group considerably reduced while the content of GLUT-4 and the activity of Na⁺K⁺-ATPase and Ca²⁺Mg²⁺-ATPase of β-CM-7 treated group increased obviously (P < 0.05). Meanwhile the cardiac indexes were significantly lessened. Thus our assay validates that the remedy employing β-CM-7 may treat diabetic cardiomyopathy with high efficacy predominantly associated with the mechanism that β-CM-7 ameliorates myocardial energy metabolism and abates free-radical-mediated oxidative stress in blood and myocardium.     

Comparative effects of β-carotene and fucoxanthin on retinol deficiency induced oxidative stress in rats

This study aimed at comparing antioxidant potential of fucoxanthin (FUCO) with β-carotene in relieving lipid peroxidation (Lpx) caused by retinol deficiency (RD) in rats. RD rats (n = 45) were fed a dose of either β-carotene (0.81 μmol) or FUCO (0.83 μmol). Plasma and liver lipid peroxide levels and activity of antioxidant enzymes catalase (CAT) and glutathione transferase (GST) were measured for 8 h. Results revealed that RD increased (P < 0.05) Lpx in plasma and liver by 34.3% and 19.4%, while the CAT activity in plasma (89%) and liver microsomes (91%) and GST in liver homogenate (31%) and liver microsomes (30%) were decreased (P < 0.05) compared to control (rats fed basal diet). FUCO suppressed (P < 0.05) the Lpx level by 7–85% (plasma) and 24–72% (liver) as compared to β-carotene (51–76%, 33–65%) over a period of 8 h. The activity of CAT in plasma and liver microsomes was higher (P < 0.05) in FUCO (90–95%, 85–93%) and β-carotene (87–96%, 79–91%) groups as compared to RD group. Similarly, the activity of GST in liver and its microsomes was also elevated (P < 0.05) in FUCO (44–51%, 22–51%) and β-carotene (19–54%, 30–43%) groups as compared to RD group. Results demonstrate that FUCO has greater potential than β-carotene in modulating Lpx, CAT, GST in plasma and liver of RD rats.     

The protective effect of peroxiredoxin II on oxidative stress induced apoptosis in pancreatic β-cells

Cell signaling mediated by morphogens is essential to coordinate growth and patterning, two key processes that govern the formation of a complex multi-cellular organism. During growth and patterning, cells are specified by both quantitative and directional information. While quantitative information regulates cell proliferation and differentiation, directional information is conveyed in the form of cell polarities instructed by local and global cues. Major morphogens like Wnts play critical roles in embryonic development and they are also important in maintaining tissue homeostasis. Abnormal regulation of these signaling events leads to a diverse array of devastating diseases including cancer. Wnts transduce their signals through several distinct pathways and they regulate vertebrate embryonic development by providing both quantitative and directional information. Here, taking the developing skeletal system as an example, we review our work on Wnt signaling pathways in various aspects of development. We focus particularly on our most recent findings that showed that in vertebrates, Wnt5a acts as a global cue to establishing planar cell polarity (PCP). Our work suggests that Wnt morphogens regulate development by integrating quantitative and directional information. Our work also provides important insights in disease like Robinow syndrome, brachydactyly type B1 (BDB1) and spina bifida, which can be caused by human mutations in the Wnt/PCP signaling pathway.     

Effects of 17β-estradiol and antioxidant administration on oxidative stress and insulin resistance in ovariectomized rats

The prevalence of insulin resistance syndrome increases during menopause with the overproduction of reactive oxygen species and impairment of the free radical scavenger function. Therefore, we investigated the effects of 17β-estradiol (E(2)) and vitamin E, as an antioxidant, on lipid peroxidation and antioxidant levels in the brain cortex and liver of ovariectomized rats as well as on insulin resistance in those rats. Forty female Sprague-Dawley rats, 3?months of age and weighing 231.5?± 9.4 g, were divided into 4 groups: sham, ovariectomized (OVX), OVX treated with E(2) (40 μg/kg subcutaneously), and OVX treated with E(2) and vitamin E (100?mg/kg intraperitoneally). The 4 groups received the appropriate treatment every day for 8?weeks. Levels of glutathione, glutathione peroxidase, superoxide dismutase , catalase, and malondialdehyde in the brain cortex and liver of ovariectomized rats were measured. Also, fasting plasma insulin, glucose, and homeostatis model assessment of insulin resistance (HOMA-IR) were determined. Malondialdehyde increased and antioxidants (glutathione, glutathione peroxidase, catalase, superoxide dismutase) decreased in the brain cortex and liver of OVX rats. Also, fasting glucose, insulin, and HOMA-IR increased in OVX rats. E(2) and E(2) plus vitamin E decreased malondialdehyde and increased antioxidants in the brain cortex and liver of OVX rats. Moreover, they decreased fasting glucose, insulin, and HOMA-IR in ovariectomized rats. This study demonstrates that E(2) and E(2) plus vitamin E supplementation to OVX rats may improve insulin resistance, strengthen the antioxidant system, and reduce lipid peroxidation.     

Suppressive effect on food intake of a potato extract (Potein®) involving cholecystokinin release in rats

We have recently reported that oral gavage of a potato extract (Potein?) suppressed the food intake in rats. The satiating effect of the potato extract was compared in the present study to other protein sources, and the involvement of endogenous cholecystokinin (CCK) secretion was examined. Food consumption was measured in 18-h fasted rats after oral gavage of the potato extract or other protein sources. The CCK-releasing activity of the potato extract was then examined in anesthetized rats with a portal cannula. Oral gavage of the potato extract reduced the food intake in the rats, the effect being greater than with casein and a soybean β-conglycinin hydrolysate. The suppressive effect on appetite of the potato extract was attenuated by treating with a CCK-receptor antagonist (devazepide). The portal CCK concentration was increased after a duodenal administration of the potato extract to anesthetized rats. These results indicate that the potato extract suppressed the food intake in rats through CCK secretion.     

Some biochemical aspects of the protective effect of strontium chloride on γ-irradiated rats

The effect of treatment with SrCl₂ (10 mg 100 g^–) on rats 15 min prior to whole body -irradiation (7.5 Gy) was studied. The hazardous effects of irradiation were greatly corrected in the treated group. The hyperglycemic effect and liver glycogen accumulation in the untreated group decreased to normal level. The enzymatic activities of serum alkaline phosphatase, alanine and aspartate aminotransferases, and lactate dehydrogenase were greatly affected, showing insignificant changes in the treated group of animals. Life span calculated on 50% survival was also significantly elongated by 36.3%. These results show the potentiality of SrCl₂ as a radioprotective agent. A proposed mechanism is discussed.     

The effect of caseinate on inclusion complexes of γ-cyclodextrin for oxidative stabilization of fish oil

In this study, we investigated that when γ-cyclodextrin (γ-CD) forms the inclusion complexes for fish oils, the oxidation stability and retardation of odor can be effectively enhanced through the addition of sodium caseinate (SC). In order to evaluate the oxidative stability and the odor-masking effect, the inclusion complexes of γ-CD and SC incorporating fish oils at various ratios were thermally-oxidized for 5 days at a storage temperature of 55°C. The use of SC on the inclusion complexes of γ-CD could improve the oxidative stability of fish oils and the masking effect of the odor. When the inclusion complexes for fish oils were composed with 80% of γ-CD and 20% of SC, the improvement effect of the oxidative stability was better compared with the complexes of other ratios. Therefore, the use of γ-CD and SC can potentially protecting sensitive ingredients such as EPA and DHA in the food industry.     

The effect of dopamine on in vitro methemoglobin formation in erythrocytes of patients with Parkinson’s disease under oxidative stress

Using electron paramagnetic resonance, the dose-dependence effect of dopamine on methemoglobin formation in erythrocytes of patients with Parkinson’s disease under the activation of oxidative stress induced by acrolein and the possibilities for the correction of this pathological process using carnosine in vitro experiments have been examined. It was shown that incubation of erythrocytes with 1.5 mM dopamine did not change the methemoglobin content, while incubation with 15 mM dopamine caused a two fold increase in the methemoglobin content compared to its initial level; 10 μM acrolein increased methemoglobin formation threefold. Administration of 15 mM dopamine and, after 1 h, 10 μM acrolein to the incubation system increased methemoglobin formation tenfold compared to its initial level. Preincubation of erythrocytes with 5 mM carnosine followed by acrolein addition prevented the increase in the methemoglobin content, while carnosine had no effect on methemoglobin formation induced by dopamine.     

The effect of carbon irradiation is associated with greater oxidative stress in mouse intestine and colon relative to γ-rays

Carbon irradiation due to its higher biological effectiveness relative to photon radiation is a concern for toxicity to proliferative normal gastrointestinal (GI) tissue after radiotherapy and long-duration space missions such as mission to Mars. Although radiation-induced oxidative stress is linked to chronic diseases such as cancer, effects of carbon irradiation on normal GI tissue have not been fully understood. This study assessed and compared chronic oxidative stress in mouse intestine and colon after different doses of carbon and γ radiation, which are qualitatively different. Mice (C57BL/6J) were exposed to 0.5 or 1.3?Gy of γ or carbon irradiation, and intestinal and colonic tissues were collected 2 months after irradiation. While part of the tissues was used for isolating epithelial cells, tissue samples were also fixed and paraffin embedded for 4 µm thick sections as well as frozen for biochemical assays. In isolated epithelial cells, reactive oxygen species and mitochondrial status were studied using fluorescent probes and flow cytometry. We assessed antioxidant enzymes and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in tissues and formalin-fixed tissue sections were stained for 4-hydroxynonenal, a lipid peroxidation marker. Data show that mitochondrial deregulation, increased NADPH oxidase activity, and decreased antioxidant activity were major contributors to carbon radiation-induced oxidative stress in mouse intestinal and colonic cells. When considered along with higher lipid peroxidation after carbon irradiation relative to γ-rays, our data have implications for functional changes in intestine and carcinogenesis in colon after carbon radiotherapy as well as space travel.     

Effect of carnosine alone or combined with α-tocopherol on hepatic steatosis and oxidative stress in fructose-induced insulin-resistant rats

A diet high in fructose (HFr) induces insulin resistance in animals. Free radicals are involved in the pathogenesis of HFr-induced insulin resistance. Carnosine (CAR) is a dipeptide with antioxidant properties. We investigated the effect of CAR alone or in combination with α-tocopherol (CAR?+?TOC) on HFr-induced insulin-resistant rats. Rats fed with HFr containing 60 % fructose received CAR (2 g/L in drinking water) with/without TOC (200 mg/kg, i.m. twice a week) for 8 weeks. Insulin resistance, serum lipids, inflammation markers, hepatic lipids, lipid peroxides, and glutathione (GSH) levels together with glutathione peroxidase (GSH-Px) and superoxide dismutase 1 (CuZnSOD; SOD1) activities and their protein expressions were measured. Hepatic histopathological examinations were performed. HFr was observed to cause insulin resistance, inflammation and hypertriglyceridemia, and increased triglyceride and lipid peroxide levels in the liver. GSH-Px activity and expression decreased, but GSH levels and SOD1 activity and expression did not alter in HFr rats. Hepatic marker enzyme activities in serum increased and marked macro- and microvesicular steatosis were seen in the liver. CAR treatment did not alter insulin resistance and hypertriglyceridemia, but it decreased steatosis and lipid peroxidation without any change in the antioxidant system of the liver. However, CAR?+?TOC treatment decreased insulin resistance, inflammation, hepatic steatosis, and lipid peroxidation and increased GSH-Px activity and expression in the liver. Our results may indicate that CAR?+?TOC treatment is more effective to decrease HFr-induced insulin resistance, inflammation, hepatic steatosis, and dysfunction and pro-oxidant status in rats than CAR alone.     

Effect of γ-radiation on some elements in certain organs of albino rats

Energy-dispersive X-ray fluorescence (EDXRF) was used to determine the concentrations of Ca, Cl, Fe, Ni, P, K, Se, S, and Zn in heart, lung, liver, spleen, and kidney of adult albino rats 2 mo after they were subject to a single gamma γ-radiation dose from⁶⁰Co at 5 gy. In female rats, K levels were significantly higher and the Ca levels significantly lower for the irradiated animals when compared to age-matched nonirradiated controls. Significant differences between irradiated and nonirradiated tissues were observed for other elements, although no sex-related differences could be found. Tissue damage and disturbances of biological functions were observed as a result of γ-irradiation.     

Protective effect of 4,4′-diaminodiphenylsulphone against oxidative stress but not to apoptotic stress in human diploid fibroblasts

Abstract

The antibiotic drug 4,4′-diaminodiphenylsulphone (DDS) is used to treat several dermatologic diseases, including Hansen's disease. This study confirmed the antioxidant nature of DDS in hydrogen peroxide (H₂O₂)-induced oxidative stress and assessed its role in other apoptotic stresses in human diploid fibroblasts (HDFs). Oxidative stress was effectively reduced by DDS in a dose-dependent manner. Moreover, the oxidative stress-induced increases in the levels of the p53 and p21 proteins were inhibited by pre-treatment with DDS. In addition, H₂O₂ and DDS increased the level of cytochrome P450 (CYP450) IIE1 in HDFs, implicating a role for DDS in H₂O₂ scavenging via the activation of CYP450. DDS treatment increased the activity of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the GSH/GSSG ratio, indicating activation of the glutathione system against oxidative stress. However, DDS showed no protective effects on HDFs against other apoptotic stimuli, such as thapsigargin and staurosporine, suggesting that DDS would act only against oxidative stress. Therefore, in addition to its antibiotic function, DDS is a potent antioxidant against H₂O₂-induced oxidative stress in HDFs.