Wound healing by topical application of antioxidant iron chelators: kojic acid and deferiprone

Kojic acid and deferiprone are iron chelators used for skin lightening and iron‐overload treatment, respectively. As iron chelation and free radical scavenging are principal factors for wound healing, it was hypothesised that the local application of these compounds might accelerate wound healing in rats. Ointments of 3%, 6% and 9% of deferiprone and kojic acid were prepared and topical treatment was performed on in vivo wound models for 12 days twice in day for test and control groups. Topical treatment with 3%, 6% and 9% showed significant improvement in wound healing after 4 days (P < 0·001). Topical application of 3% and 6% deferiprone enhanced wound healing after 8 days (P < 0·026 and P < 0·001, respectively). Accelerated wound healing was seen using 3% and 6% deferiprone after 12 days (P = 0·003 and P < 0·001, respectively). DPPH scavenging assay was also performed to compare the antioxidant potencies of kojic acid and deferiprone. Deferiprone had more free radical scavenging power than kojic acid. Generally, deferiprone topical treatment, accelerated wound healing more than kojic acid because of its higher antioxidant and iron chelation abilities.     

The antioxidant tempol decreases acute pulmonary thromboembolism-induced hemolysis and nitric oxide consumption

Introduction

Acute pulmonary thromboembolism (APT) is a critical condition associated with acute pulmonary hypertension. Recent studies suggest that oxidative stress and hemolysis contribute to APT-induced pulmonary hypertension, possibly as a result of increased nitric oxide (NO) consumption. We hypothesized that the antioxidant tempol could attenuate APT-induced hemolysis, and therefore attenuate APT-induced increases in plasma NO consumption.

Materials and Methods

APT was induced in anesthetized sheep with autologous blood clots. The hemodynamic effects of tempol infused at 1.0 mg/kg/min 30 min after APT were determined. Hemodynamic measurements were carried out every 15 min. To assess oxidative stress, serum 8-isoprostanes levels were measured by ELISA. Plasma cell-free hemoglobin concentrations and NO consumption by plasma samples were determined. An in vitro oxidative AAPH-induced hemolysis assay was used to further validate the in vivo effects of tempol.

Results

APT caused pulmonary hypertension, and increased pulmonary vascular resistance in proportion with the increases in 8-isoprostanes, plasma cell-free hemoglobin concentrations, and NO consumption by plasma (all P < 0.05). Tempol attenuated the hemodynamic alterations by approximately 15-20% and blunted APT-induced increases in 8-isoprostanes, in cell-free hemoglobin concentrations, and the increases in NO consumption by plasma (P < 0.05). Tempol dose-dependently attenuated AAPH-induced in vitro hemolysis (P < 0.05).

Conclusions

Our findings are consistent with the idea that antioxidant properties of tempol decrease APT-induced hemolysis and nitric oxide consumption, thus attenuating APT-induced pulmonary hypertension.     

Bromocriptine prevents neuron damage following inhibition of superoxide dismutase in cultured ventral spinal cord neurons

Abstract

Rpsen et al. have reported point mutations in the cytosolic Cu/Zn superoxide dismutase (SOD 1) gene in some families with familial amyotrophic lateral sclerosis (ALS). To determine whether decreased SOD activity could contribute to neuronal damage, rat embryo ventral spinal cord neurons were incubated with diethyldithiocarbamate (DOC), an inhibitor of SOD. There was a marked increase in neuronal damage in cultures exposed to DOC and this phenomenon was dose-related. In this paradigm, these deteriorative changes were prevented by bromocriptine. DOC-treated ventral spinal cord neurons provide an in vitro model of free radical neurotoxicity secondary to decreased SOD activity. Simultaneous treatment with bromocriptine and DOC reduced neurotoxicity, indicating that bromocriptine has a neuroprotective effect against free radicals. [Neural Res 1997; 19: 389-392]     

Selenium Ameliorates Ibuprofen Induced Testicular Toxicity by Redox Regulation: Running Head: Se protects against NSAID induced testicular toxicity

Despite the Cox inhibitory anti-inflammatory and antipyretic effects of most widely used non-steroidal anti-inflammatory drugs (NSAIDs), such as Ibuprofen, their chronic use is associated with a plethora of patho-physiological insults. One such toxic effect on testicular tissues is not well studied and the underlying molecular mechanisms remain unexplored. Thus, the current study is designed to evaluate the antioxidant properties of essential trace element selenium (Se) to ameliorative Ibuprofen associated testicular toxic effects. Adult male Wistar rats were divided into 3 groups and fed on diets containing different concentrations of sodium selenite, viz. 0.01 mg/kg (Se- deficient), 0.2 mg/kg (Se-adequate), or 0.5 mg/kg (Se- supplemented) for 8 weeks. After diet feeding schedule, each group was divided into two subgroups i.e., with or without the treatment of Ibuprofen (120 mg/kg Bw). The protective effect of Se was evaluated by measuring testicular Se and selenoproteins status, spermatogenic markers, histopathology and testicular redox status. Ibuprofen diminished seminal volume, sperm count, sperm motility, which correlated well increased testicular reactive oxygen species. Se deficiency exacerbated these detrimental effects of ibuprofen by increasing oxidative stress. Alternatively, Se supplementation through antioxidant enzymes mediated protective effects. Se as essential antioxidant selenoproteins ameliorates Ibuprofen induced male reproductive toxicity.     

Gallic acid protects against cyclophosphamide‐induced toxicity in testis and epididymis of rats

The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg^?1 for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg^?1 on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg^?1) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg^?1 for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione‐S‐transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA‐treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.     

Lipid profile,inflammation, and oxidative status in peri- and postmenopausal women

Objective: To evaluate the effect of perimenopause and postmenopause on lipid profile, inflammation, and oxidative stress in women.

Methods: This cross-sectional study included 117 women (47?±?6 years) classified as perimenopausal (n?=?47), postmenopausal (n?=?40), or non-menopausal (n?=?30). In serum, we analyzed lipid profile, tumor necrosis factor-alpha (TNF-α), interleukin-1α (IL-1α), and C-reactive protein (CRP). Pro-oxidant status was assessed by thiobarbituric acid reactive substances (TBARS) and protein carbonyls. Antioxidant defense was performed by analysis of superoxide dismutase (SOD) and catalase activities.

Results: Compared to non-menopausal women, triacylglycerols (TG) were similar, total cholesterol and LDL-C were higher in perimenopausal and postmenopausal women, while HDL-C concentrations were decreased. TNF-α and IL-1α were higher in postmenopausal women, while CRP concentrations were elevated in both peri-and postmenopausal women (p?p?p?Conclusion: Menopausal transition and postmenopause were associated with dyslipidemia, inflammation, and unbalanced oxidative status exposing women to cardiovascular risk.     

Evaluation of the protective effects of hesperetin against cisplatin-induced ototoxicity in a rat animal model

ObjectivesWe aimed to investigate the effects of hesperetin as a flavanon both histopathologically and immunohistochemically on cochlear apoptosis in a rat model of cisplatin-induced ototoxicity (CIO). The evaluation of the effects of hesperetin on cisplatin-induced hearing loss was performed using distortion product otoacoustic emission (DPOAE).MethodsTwenty-eight wistar albino rats were used in the current study. The rats were randomly divided into four groups with seven rats in each group. Group C was exposed to a single dose of cisplatin (12 mg/kg) by intraperitoneal injection. Group CH received intraperitoneally cisplatin (12 mg/kg) and hesperetin (20 mg/kg). Group H was exposed to hesperetin (20 mg/kg) intraperitoneally. The sham group (group S) received normal saline (6 cc) intraperitoneally. The measurements of DPOAE and signal-noise ratios (SNR) were performed before the treatment and again on the first and 6 days after administration of the drugs. Rats were sacrificed and cochleae were dissected 10 days after drug administration. The cochlear tissue was assessed in all groups by histopathologic, immunohistochemical and TUNEL assay. In addition, serum oxidative stress markers and antioxidant parameters were analyzed.ResultsThere was a significant difference between the basal value and the sixth day at frequencies 8.4, 9.6 and 9.96 for group C. We also found a significant difference between the first and sixth day at frequencies 7.2, 8.4, 9.6 and 9.96. On the 6th day, there were significant differences between C and S groups at all frequencies except 2.4. We showed a significant difference between C and H groups at frequencies 4.8, 6.0, 8.4, 9.6 and 9.96. There was also a significant difference between C and CH groups at frequencies 2.4, and 3.6. We found lower levels of oxidants and higher levels of antioxidants in CH group as compared to C group. C group had a significantly greater number of TUNEL-positive cells than did S, H and CH groups. The number of TUNEL-positive cells in CH group was higher than in S and H groups. There was a significant difference between the positive PCNA cells of CH group compared to S and H groups in spiral ganglion and stria vascularis. In addition, there were no positive PCNA cells in C group.ConclusionsHesperetin may prevent ototoxicity by increased antioxidant enzymes and reduced oxidant parameters and protected against apoptosis resulting from a proliferation of cochlear cells in CIO.     

地鳖多糖提取物的体内外抗氧化作用

【摘要】 目的 研究地鳖多糖提取物体内外抗氧化作用。 方法 体外试验通过采用分光光度法、邻苯三酚自氧化法和Fe2 -邻二氮菲法分别检测地鳖多糖对二苯代苦味酰基自由基(DPPH?)、超氧阴离子自由基（O2-?）和羟自由基（OH?）的清除,检测体外红细胞氧化溶血和肝脏线粒体肿胀程度。体内试验采用小鼠连续灌胃不同剂量（0、40、80、160mg/kg）地鳖多糖提取物20天,硫代巴比妥酸（TBA）比色法法测定小鼠不同组织丙二醛（MDA）含量,分光光度法检测抗氧化酶（SOD、CAT、GSH-PX）活力 结果 与对照组比较,地鳖多糖组对自由基（DPPH?、O2-?和OH?）清除率随多糖浓度升高而显著提高;地鳖多糖浓度在0.4~2mg/mL范围内其对铁还原力逐渐提高;体外红细胞氧化溶血和线粒体肿胀显著降低。多糖组小鼠肝肾组织和血清中MDA含量降低,SOD、CAT、GSH-PX抗氧化酶活力提高并明显高于对照组。结论 地鳖多糖提取物能够清除自由基,降低自由基引起细胞氧化损伤,抑制组织中过氧化物生成,提高抗氧化酶活力,具有显著的体内外抗氧化作用。     

Serum levels of bcl-2 and cellular oxidative stress in patients with viral hepatitis

PURPOSE: This study was conducted to investigate the presence of bcl-2 protein in the serum of patients with viral hepatitis and to find out if there is any correlation between bcl-2 protein levels and cellular oxidative stress in the pathogenesis of viral hepatitis. METHODS: This study was carried out on 130 patients with viral hepatitis, 70 with chronic hepatitis, 30 with liver cirrhosis and 30 with hepatocellular carcinoma (HCC) in addition to 20 healthy persons as the control. Serum bcl-2 protein was estimated by enzyme-linked immunosorbent assay, serum malondialdehyde (MDA), nitric oxide (NO) and antioxidant enzymes (GSH, GSH-px, GR and SOD) were measured using spectrophotometric analysis. RESULTS: bcl-2 protein level was significantly elevated in the serum of HCC, cirrhosis and chronic hepatitis groups as compared to control group. There were significant positive correlations between higher bcl-2 protein level and viral hepatitis markers (HBsAg, anti-HCV antibodies) in HCC and cirrhotic patients as compared to chronic hepatitis group. An increase in oxidative stress markers (MDA, NO) and a decrease in antioxidant enzyme activities (SOD, GSH and GSH-px) were observed. However, there was a negative correlation between bcl-2 levels and GR in all studied patient groups. CONCLUSIONS: The release of oxidative free radicals, deficiency in antioxidant enzymes and the expression of bcl-2 protein might play a role in the pathogenesis of viral hepatitis. The ability to measure bcl-2 protein in the serum could be useful as a prognostic marker of cancer patients.