[Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Catalase and interleukin-6 serum elevation in a prediction of treatment-resistance in male schizophrenia patients.

BACKGROUND: Oxidative stress (OS) and neuroinflammatory pathways play an important role in the pathophysiology of schizophrenia. The present study investigated the relationship between OS, inflammatory cytokines, and clinical features in male patients with treatment-resistant schizophrenia (TRS). METHOD: We measured plasma OS parameters, including manganese-superoxide dismutase (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD), total-SOD (T-SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px); and serum inflammatory cytokines, including interleukin (IL)- 1α, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)-γ, from 80 male patients with chronic schizophrenia (31 had TRS and 49 had chronic stable schizophrenia (CSS)), and 42 healthy controls. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, plasma Mn-SOD, CuZn-SOD, T-SOD, GSH-Px, and MDA levels were significantly lower, while CAT and serum IL-6 levels were higher in both TRS and CSS male patients (all P < 0.05). Significant differences in the activities of CAT (F = 6.068, P = 0.016) and IL-6 levels (F = 6.876, P = 0.011) were observed between TRS and CSS male patients after analysis of covariance. Moreover, a significant positive correlation was found between IL-6 levels and PANSS general psychopathology subscores (r = 0.485, P = 0.006) and between CAT activity and PANSS total scores (r = 0.409, P = 0.022) in TRS male patients. CAT and IL-6 levels were predictors for TRS. Additionally, in chronic schizophrenia patients, a significant positive correlation was observed between IL-6 and GSH-Px (r = 0.292, P = 0.012), and the interaction effect of IL-6 and GSH-Px was positively associated with PANSS general psychopathology scores (r = 0.287, P = 0.014). CONCLUSION: This preliminary study indicated that variations in OS and inflammatory cytokines may be involved in psychopathology for patients with chronic schizophrenia, especially in male patients with TRS.

Effect of Normobaric Hypoxia on Alterations in Redox Homeostasis, Nitrosative Stress, Inflammation, and Lysosomal Function following Acute Physical Exercise.

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects of normoxia and hypoxia during acute physical exercise. The study is aimed at evaluating the relationship between enzymatic and nonenzymatic antioxidant barrier, total antioxidant/oxidant status, oxidative and nitrosative damage, inflammation, and lysosomal function in different acute exercise protocols under normoxia and hypoxia. Fifteen competitive athletes were recruited for the study. They were subjected to two types of acute cycling exercise with different intensities and durations: graded exercise until exhaustion (GE) and simulated 30 km individual time trial (TT). Both exercise protocols were performed under normoxic and hypoxic (FiO2 = 16.5%) conditions. The number of subjects was determined based on our previous experiment, assuming the test power = 0.8 and α = 0.05. We demonstrated enhanced enzymatic antioxidant systems during hypoxic exercise (GE: ↑ catalase (CAT), ↑ superoxide dismutase; TT: ↑ CAT) with a concomitant decrease in plasma reduced glutathione. In athletes exercising in hypoxia, redox status was shifted in favor of oxidation reactions (GE: ↑ total oxidant status, ↓ redox ratio), leading to increased oxidation/nitration of proteins (GE: ↑ advanced oxidation protein products (AOPP), ↑ ischemia-modified albumin, ↑ 3-nitrotyrosine, ↑ S-nitrosothiols; TT: ↑ AOPP) and lipids (GE: ↑ malondialdehyde). Concentrations of nitric oxide and its metabolites (peroxynitrite) were significantly higher in the plasma of hypoxic exercisers with an associated increase in inflammatory mediators (GE: ↑ myeloperoxidase, ↑ tumor necrosis factor-alpha) and lysosomal exoglycosidase activity (GE: ↑ N-acetyl-ß-hexosaminidase, ↑ ß-glucuronidase). Our study indicates that even a single intensive exercise session disrupts the antioxidant barrier and leads to increased oxidative and nitrosative damage at the systemic level. High-intensity exercise until exhaustion (GE) alters redox homeostasis more than the less intense exercise (TT, near the anaerobic threshold) of longer duration (20.2 ± 1.9 min vs. 61.1 ± 5.4 min-normoxia; 18.0 ± 1.9 min vs. 63.7 ± 3.0 min-hypoxia), while hypoxia significantly exacerbates oxidative stress, inflammation, and lysosomal dysfunction in athletic subjects.

Ginseng alleviates folliculogenesis disorders via induction of cell proliferation and downregulation of apoptotic markers in nicotine-treated mice.

BACKGROUND: Ginseng is a powerful phytoestrogen with high antioxidant properties. OBJECTIVE: This study aimed to evaluate the effect of Panax Ginseng (PG) on folliculogenesis, proliferation, and apoptosis in the ovary impaired by nicotine. METHODS: Forty adult mice were divided into five groups. Control, sham, and nicotine groups, and co-treated groups of nicotine and ginseng in doses of 0.5 and 1 g/kg. Folliculogenesis was assessed via histopathology and serum evaluation of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) by ELISA. Lipid peroxidation and antioxidant enzyme activities both in homogenate tissue and serum were assayed by colorimetric analysis. Apoptotic markers of cytochrome c (Cyt c), Bax, and Bcl-2 were evaluated by RT-PCR. Proliferative index was studied by the Ki-67 immunostaining procedure. RESULTS: In comparison to the control or sham groups, nicotine significantly reduced the levels of FSH, LH, and estradiol hormones. An insignificant reduction was observed in the progesterone hormone. Nicotine reduced all healthy follicle numbers, except primordial (P = 0.001). Malondialdehyde (MDA) was increased in tissue and serum in the nicotine group (P = 0.01). Serum catalase (CAT) and enzymatic activity of superoxide dismutase (SOD) both were reduced in tissue and the serum, in the nicotine group. Nicotine induced a reduction in the proliferative indexes of granulosa and theca cells in pre-antral and antral follicles (P = 0.001). However, its effect on the proliferative index of stroma cells was not significant. Apoptotic markers were elevated in the nicotine group (P = 0.001). Co-treatment with ginseng elevated all sex hormones, increased healthy follicles, and reduced tissue or serum lipid peroxidation, compared with the nicotine group (p < 0.05). Co-Treatment with ginseng also reduced the expression of apoptotic markers and increased the proliferative indexes in granulosa and theca cells in pre-antral and antral follicles and also in stroma cells, in comparison to the nicotine group (P = 0.001). All above-mentioned alterations following treatment with ginseng were remarkable, especially in the dose of 1 g/kg. CONCLUSION: This study showed ginseng protects folliculogenesis via alteration of hypothalamic- pituitary-gonadal (HPG) axis, induction of proliferation in ovarian somatic cells, reduction of lipid peroxidation, and downregulation of apoptotic markers in the mouse ovary, treated with nicotine.

Vitamin D3 supplementation alleviates chemically-induced cirrhosis-associated hepatocarcinogenesis.

Vitamin D3 (VD3) deficiency has been associated with increased risk for cirrhosis and hepatocellular carcinoma, a highly incident malignant neoplasia worldwide. On the other hand, VD3 supplementation has shown some beneficial effects in clinical studies and rodent models of chronic liver disease. However, preventive effects of dietary VD3 supplementation in cirrhosis-associated hepatocarcinogenesis is still unknow. To investigate this purpose, male Wistar rats submitted to a combined diethylnitrosamine- and thioacetamide-induced model were concomitantly supplemented with VD3 (5,000 and 10,000 IU/kg diet) for 25 weeks. Liver samples were collected for histological, biochemical and molecular analysis. Serum samples were used to measure 25-hydroxyvitamin D [25(OH)D] and alanine aminotransferase levels. Both VD3 interventions decreased hepatic collagen deposition and pro-inflammatory p65 protein levels, while increased hepatic antioxidant catalase and glutathione peroxidase activities and serum 25(OH)D, without a clear dose-response effect. Nonetheless, only the highest concentration of VD3 increased hepatic protein levels of VD receptor, while decreased the number of large preneoplastic glutathione-S-transferase- (>0.5 mm²) and keratin 8/18-positive lesions, as well the multiplicity of hepatocellular adenomas. Moreover, this intervention increased hepatic antioxidant Nrf2 protein levels and glutathione-S-transferase activity. In summary, dietary VD3 supplementation - in special the highest intervention - showed antifibrotic and antineoplastic properties in chemically-induced cirrhosis-associated hepatocarcinogenesis. The positive modulation of Nrf2 antioxidant axis may be mechanistically involved with these beneficial effects, and may guide future clinical studies.

Effect of Lactobacillus fermentum HFY03 on the Antifatigue and Antioxidation Ability of Running Exhausted Mice.

Yak yogurt is mainly produced in Qinghai-Tibet Plateau. It is a kind of naturally fermented dairy product. It contains abundant microorganisms. Lactobacillus fermentum (LF) HFY03 is a lactic acid bacteria derived from it. Our main research content is to study the influence of LF-HFY03 on the antifatigue and antioxidation ability of running exhausted mice. We gave different doses of LF-HFY03 to mice by gavage for 4 weeks. We selected vitamin C as the positive control group, mainly to study the relationship between antioxidant capacity and fatigue resistance and LF-HFY03 in mice with running exhaustion. The results showed that LF-HFY03 and vitamin C could significantly improve the running time of mice. And with the increase in LF-HFY03 concentration, the exhaustion time of mice was also extended. LF-HFY03 can reduce the content of urea nitrogen and lactic acid and also can increase the content of free fatty acids and liver glycogen. The levels of alanine aminotransferase, serum creatine kinase, and aspartate aminotransferase in mice decreased gradually as the antioxidant peptide level of walnut albumin increased. LF-HFY03 can reduce malondialdehyde (MDA) levels in a quantification-dependent manner and can also increase catalase (CAT) and superoxide dismutase (SOD) levels. LF-HFY03 can also increase the expressions of CAT mRNA, Cu/Zn-SOD, and Mn-SOD in the liver of mice. At the same time, LF-HFY03 can also increase the expression of protein of threonine transporter 1 (AST1)/alanine/cysteine/serine, mRNA, nNOS, and eNOS. At the same time, the solution could reduce the expression of TNF-α, syncytin-1, and inducible nitric oxide synthase (iNOS). The results showed that LF-HFY03 has a high development and application prospect as an antifatigue probiotic nutritional supplement.

Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System.

Numerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destruction and the related mechanisms therein are not yet fully understood. Here, we explored the impacts of supplemental ASTX on periodontal destruction and systemic complications in type I diabetic mice. To induce diabetes, C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg), and the hyperglycemic mice were orally administered with ASTX (12.5 mg/kg) (STZ+ASTX group) or vehicle only (STZ group) daily for 60 days. Supplemental ASTX did not improve hyperglycemic condition, but ameliorated excessive water and feed consumptions and lethality in STZ-induced diabetic mice. Compared with the non-diabetic and STZ+ASTX groups, the STZ group exhibited severe periodontal destruction. Oral gavage with ASTX inhibited osteoclastic formation and the expression of receptor activator of nuclear factor (NF)-κB ligand, 8-OHdG, γ-H2AX, cyclooxygenase 2, and interleukin-1ß in the periodontium of STZ-injected mice. Supplemental ASTX not only increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and osteogenic transcription factors in the periodontium, but also recovered circulating lymphocytes and endogenous antioxidant enzyme activity in the blood of STZ-injected mice. Furthermore, the addition of ASTX blocked advanced glycation end products-induced oxidative stress and growth inhibition in human-derived periodontal ligament cells by upregulating the Nrf2 pathway. Together, our results suggest that ASTX does not directly improve hyperglycemia, but ameliorates hyperglycemia-triggered periodontal destruction and oxidative systemic complications in type I diabetes.

Early (5-Day) Onset of Diabetes Mellitus Causes Degeneration of Photoreceptor Cells, Overexpression of Incretins, and Increased Cellular Bioenergetics in Rat Retina.

The effects of early (5-day) onset of diabetes mellitus (DM) on retina ultrastructure and cellular bioenergetics were examined. The retinas of streptozotocin-induced diabetic rats were compared to those of non-diabetic rats using light and transmission electron microscopy. Tissue localization of glucagon-like-peptide-1 (GLP-1), exendin-4 (EXE-4), and catalase (CAT) in non-diabetic and diabetic rat retinas was conducted using immunohistochemistry, while the retinal and plasma concentration of GLP-1, EXE-4, and CAT were measured with ELISA. Lipid profiles and kidney and liver function markers were measured from the blood of non-diabetic and diabetic rats with an automated biochemical analyzer. Oxygen consumption was monitored using a phosphorescence analyzer, and the adenosine triphosphate (ATP) level was determined using the Enliten ATP assay kit. Blood glucose and cholesterol levels were significantly higher in diabetic rats compared to control. The number of degenerated photoreceptor cells was significantly higher in the diabetic rat retina. Tissue levels of EXE-4, GLP-1 and CAT were significantly (p = 0.002) higher in diabetic rat retina compared to non-diabetic controls. Retinal cellular respiration was 50% higher (p = 0.004) in diabetic (0.53 ± 0.16 µM O2 min-1 mg-1, n = 10) than in non-diabetic rats (0.35 ± 0.07 µM O2 min-1 mg-1, n = 11). Retinal cellular ATP was 76% higher (p = 0.077) in diabetic (205 ± 113 pmol mg-1, n = 10) than in non-diabetic rats (116 ± 99 pmol mg-1, n = 12). Thus, acute (5-day) or early onslaught of diabetes-induced hyperglycemia increased incretins and antioxidant levels and oxidative phosphorylation. All of these events could transiently preserve retinal function during the early phase of the progression of diabetes.

Prophylactic effect of myricetin and apigenin against lipopolysaccharide-induced acute liver injury.

BACKGROUND: Liver has an important role in the initiation and progression of multiple organ failure that occurs in sepsis. Many natural active substances can be used to reduce the liver injury caused by sepsis. For this aim, the effects of myricetin and apigenin on mice model of acute liver injury was evaluated in this study. METHODS AND RESULTS: Thirty-six mice were randomly divided into six groups as; control, lipopolysaccharide (LPS) (5 mg/kg), LPS + myricetin (100 mg/kg), LPS + myricetin (200 mg/kg), LPS + apigenin (100 mg/kg), and LPS + apigenin (200 mg/kg) groups. Myricetin and apigenin were administered orally for 7 days, and LPS was administered intraperitoneally only on the 7th day of the study. 24 h after LPS application, all animals were sacrificed and serum biochemical parameters, histopathology and oxidative stress and inflammation markers of liver tissue were examined. Myricetin and apigenin pre-treatments increased serum albumin and total protein levels, liver GSH level and catalase and SOD activities and decreased serum ALT, AST, ALP, γ-GT, CRP, total and direct bilirubin levels, liver MPO activity, MDA, NOx, PGE2, TNF-α, IL-1ß, and IL-6 levels, iNOS and COX-2 mRNA levels, phosphorylation of NF-κB p65, IκB, and IKK proteins but not p38, ERK, and JNK proteins in LPS-treated mice. Myricetin and apigenin administration also regained the hepatic architecture disrupted during LPS application. CONCLUSION: Myricetin and apigenin pre-treatments led to reduction of liver injury indices and oxidative stress and inflammatory events and these flavonoids has probably hepatoprotective effects in acute liver injury.

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma.

Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p < 0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49 ± 4.7 vs. 67.93 ± 8.8, p < 0.001), AOPP (137.64 ± 21.9 vs. 119.08 ± 33.1, p < 0.001), MDA (3.56 ± 0.30 vs. 3.05 ± 0.33, p < 0.001), and ox-LDL (19.78 ± 0.97 vs. 16.94 ± 1.02, p < 0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d = -2.853, 95% CI 2.50-3.19) and MDA (d = -1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5 ± 156.7 vs. 1239.3 ± 290, p < 0.001) and CAT (2.34 ± 0.34 vs. 2.63 ± 0.38, p < 0.001), GPx (102.37 ± 6.58 vs. 108.03 ± 6.95, p < 0.001), and SOD (5.13 ± 0.39 vs. 5.53 ± 0.31, p < 0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d = 1.135, 95% CI 0.46-0.34) and GPx (d = 0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.

Redox State and Lysosomal Activity in Women with Ovarian Cancer with Tumor Recurrence and Multiorgan Metastasis.

The aim of the study is to evaluate oxidant-antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α1-antitrypsin, were studied in serum. The vitamin E and 8-iso-prostaglandin F2α concentrations as well as arylsulfatase activity were lower in the women with cancer compared to the controls (p = 0.006, p = 0.03, p = 0.001, respectively). In contrast, cathepsin D activity was lower in the controls (p = 0.04). In the peripheral blood of the women with cancer, oxidant-antioxidant and lysosomal disturbances were observed.

Ameliorative effects of fisetin in letrozole-induced rat model of polycystic ovary syndrome.

BACKGROUND: The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS). METHODOLOGY: Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method. RESULTS: Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS. CONCLUSION: Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene.

The widespread use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites in food for human consumption and thus pose a threat to human health. It has been found that glyphosate reduces energy metabolism in the brain, its amount increases in white muscle fibers. At the same time, the effect of chronic use of glyphosate on the dynamic properties of skeletal muscles remains practically unexplored. The selected biomechanical parameters (the integrated power of muscle contraction, the time of reaching the muscle contraction force its maximum value and the reduction of the force response by 50% and 25% of the initial values during stimulation) of muscle soleus contraction in rats, as well as blood biochemical parameters (the levels of creatinine, creatine phosphokinase, lactate, lactate dehydrogenase, thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione and catalase) were analyzed after chronic glyphosate intoxication (oral administration at a dose of 10 µg/kg of animal weight) for 30 days. Water-soluble C60 fullerene, as a poweful antioxidant, was used as a therapeutic nanoagent throughout the entire period of intoxication with the above herbicide (oral administration at doses of 0.5 or 1 mg/kg). The data obtained show that the introduction of C60 fullerene at a dose of 0.5 mg/kg reduces the degree of pathological changes by 40-45%. Increasing the dose of C60 fullerene to 1 mg/kg increases the therapeutic effect by 55-65%, normalizing the studied biomechanical and biochemical parameters. Thus, C60 fullerenes can be effective nanotherapeutics in the treatment of glyphosate-based herbicide poisoning.

Dietary dihydromyricetin supplementation enhances antioxidant capacity and improves lipid metabolism in finishing pigs.

Nowadays, chronic diseases have become a potential danger to human health and are highly concerning. Given that pigs are a suitable animal model for human nutrition and metabolism for its similar anatomical and physiological properties to those of humans, this study has used 24 castrated male Duroc × Landrace × Yorkshire (DLY) pigs as experimental subjects to explore the effects of dietary dihydromyricetin (DHM) supplementation on the antioxidant capacity and lipid metabolism. Results showed that dietary 300 and 500 mg DHM kg-1 diet supplementation increased the serum total superoxide dismutase (T-SOD) level, serum and liver reduced glutathione (GSH), muscle catalase (CAT) level and serum high-density lipoprotein cholesterol (HDL-C) level, and reduced the liver malondialdehyde (MDA) level and muscle triglyceride (TG) level in finishing pigs. Western blot analysis showed that dietary DHM supplementation activated the nuclear-related factor 2 (Nrf2) and AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signals. Real-time quantitative PCR analysis showed that dietary DHM supplementation upregulated the mRNA levels of lipolysis and fatty acid oxidation-related genes, and down-regulated the mRNA expression of lipogenesis-related genes in finishing pigs. Together, we provide evidence that dietary DHM supplementation improved the antioxidant capacity and lipid metabolism in finishing pigs.

Effects of nerol on paracetamol-induced liver damage in Wistar albino rats.

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.

The effects of melatonin treatment on oxidative stress induced by ovariohysterectomy in dogs.

BACKGROUND: As one of the most common surgeries performed in veterinary medicine, ovariohysterectomy (OHE) can induce oxidative stress in dogs. The antioxidant properties of melatonin have been confirmed in various studies. This study aimed to investigate the effects of melatonin administration on oxidative stress in dogs before and after OHE. In this study, 25 mature female intact dogs were selected and randomly divided into five equal groups: Melatonin (melatonin, no surgery), OHE (no melatonin, surgery), OHE + melatonin (melatonin, surgery), anesthesia+melatonin (melatonin, sham surgery), and control (no melatonin, no surgery) groups. Melatonin (0.3 mg/Kg/day, p.o.) was administrated to the dogs in the melatonin, OHE + melatonin, and anesthesia+melatonin groups on days - 1, 0, 1, 2, and 3 (day 0 = OHE). Blood sampling was performed on days - 1, 1, 3, and 5 of the study. Blood samples were immediately transferred to the laboratory and sera were separated and stored at - 20 °C. Superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and malondialdehyde (MDA) concentrations were measured with commercial kits. RESULTS: The levels of SOD, GPX and CAT were significantly higher in the melatonin and anesthesia+melatonin groups compared to those of the control group at days 3 and 5. The level of antioxidant enzymes significantly decreased in the OHE group compared to that of other groups at days 3 and 5. The administration of melatonin increased the level of antioxidant enzymes in ovariohysterectomized dogs. Ovariohysterectomy significantly increased the concentration of MDA in comparison to that of other groups at day 3. Melatonin administration significantly decreased the level of MDA in melatonin, anesthetized, and ovariohysterectomized dogs at day 3. CONCLUSIONS: Administration of melatonin on day - 1, 0, 1, 2 and 3 modulate the oxidative stress induced by OHE in dogs by increasing antioxidant enzymes concentration and decreasing MDA levels.

The effects of L-carnitine on renal function and gene expression of caspase-9 and Bcl-2 in monosodium glutamate-induced rats.

BACKGROUND: Monosodium glutamate (MSG) is frequently consumed as a flavor enhancer or food additive. Possible damages induced by MSG effects on some organs have been stated in experimental animal models. The aim of the present study was to evaluate the protective effects of L-carnitine (L-ca) on the renal tissue in MSG-Induced Rats. METHODS: In this regard, 60 male rats were randomly divided into six groups (n = 10/each): 1 (Control); 2 (sham); 3 (L-carnitine 200 mg/kg b.w); 4 (MSG 3 g/kg b.w); 5 (MSG + L-carnitine 100 mg/kg); and 6 (MSG + L-carnitine 200 mg/kg). After 6 months, the rats were sacrificed, the blood sample collected and the kidneys harvested for evaluation of biochemical analytes, genes expression, and histopathological changes. RESULTS: MSG significantly increased the serum level of MDA, BUN, creatinine, uric acid and renal Caspase-9, NGAL and KIM-1 expression, but it decreased the serum activity also renal expression of SOD, catalase, GPX, and Bcl-2 expression compared to the control group. Treatment with L-ca significantly reduced the serum BUN, creatinine, uric acid and MDA level and increased catalase, GPX and SOD compared to the MSG group. However, only administration of L-ca 200 significantly decreased the caspase-9, NGAL and KIM-1; also, it increased the Bcl-2 expression in the kidney compared to the MSG group. CONCLUSIONS: Our findings indicated that L-carnitine had a major impact on the cell protection and might be an effective therapy in ameliorating the complications of the kidney induced by MSG via its antioxidant and anti-apoptotic properties.

Assessment of reproductive toxicity and genotoxicity of Aconiti Lateralis Radix Praeparata and its processed products in male mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconiti Lateralis Radix Praeparata (Chinese name: Fuzi), the root of Aconitum carmichaelii Debx., is a representative medicine for restoring yang and rescuing patient from collapse. However, less studies had been reported on the reproductive toxicity and genotoxicity of Fuzi. According to the principle of reducing toxicity and preserving efficiency, only processed products of Fuzi are commonly applied in clinic, including Baifupian, Heishunpian and Danfupian. However, whether processing could alleviate the reproductive toxicity and genotoxicity of Fuzi had not been revealed. AIM OF THE STUDY: To assess the effect and possible mechanism of Fuzi and its processed products on reproductive toxicity and genotoxicity in male mice. MATERIALS AND METHODS: Aqueous extracts of Fuzi and its processed products (Baifupian, Heishunpian and Danfupian, 5.85 g/kg) were administrated by gavage once daily for fourteen consecutive days. The reproductive toxicity was evaluated by testis weight, testis ratio, testis histopathology, sperm count, sperm viability rate and sperm deformity rate. The genotoxicity was evaluated by comet assay and micronucleus test in sperm, peripheral blood cell and bone marrow cell. Possible mechanisms of attenuating toxicity by processing were analyzed by detecting the level of testosterone, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and catalase (CAT). RESULTS: Fuzi significantly caused different degrees of reproductive toxicity and genotoxicity, specifically reducing the weight and testicular coefficient of testis, causing obvious pathological changes in testicular tissue, reducing sperm count and sperm viability rate, increasing sperm deformity rate and DNA damage in sperm/peripheral blood cells/bone marrow cells. Moreover, Fuzi decreased the level of testosterone, SOD, GSH and CAT, while increased the level of MDA in serum. Notably, the reproductive toxicity and genotoxicity induced by the processed products, especially Heishunpian and Danfupian, were significantly lowered compared to Fuzi. Processing could increase the level of testosterone, SOD, GSH, CAT and decrease the level of MDA compared to Fuzi. CONCLUSION: Fuzi and its processed products had reproductive toxicity and genotoxicity, but the toxicity of processed products was significantly weakened compared to Fuzi. The protective mechanism of processing to reduce the toxicity of Fuzi might be related to increasing the level of testosterone and decreasing oxidative stress.

The Impact of Hepatitis C Virus Genotypes on Oxidative Stress Markers and Catalase Activity.

Hepatitis C virus (HCV) is a major cause of liver disease worldwide. Chronic HCV infections are usually associated with increased oxidative stress in the liver tissue. The intensity of oxidative stress may be a detrimental factor in liver injury and may determine the severity of the disease. The aim of the present case-control study was to determine the level of lipid peroxidation (TBARS), protein oxidative modification (AOPP), and catalase activity in sera of patients infected with HCV, in relation to different HCV genotypes and viral load. Considering the HCV patients with chronic hepatitis C (52) and control subject (50) recruitment, the study was designed as a case-control-type. The HCV RNA isolation, viral load, and HCV genotyping were performed according to the standard protocols. A significant difference compared to control healthy subjects was reported for TBAR (p < 0.001), AOPP (p = 0.001), and catalase activity (p = 0.007). In a gender-based comparison, a significantly higher level of AOPP for females was reported (p < 0.001). As stratified by HCV genotype, the most common was HCV-1 (HCV-1a and HCV 1b), with the overall participation of more than 60%, followed by genotype 3, while the least represented was genotype 2. No significant difference was documented among genotypes in regard to oxidative stress markers, although somewhat higher TBARS level, but not significant, was registered in patients infected with genotype 1b. A statistically significant positive correlation was found between the concentration of HCV genome copies and AOPP (r = 0.344; p = 0.012). A high level of HCV viral load was more likely to have a higher TBARS, but still without statistical significance (p = 0.072). In conclusion, the results obtained confirmed an imbalance between the ROS production and antioxidative defense system in HCV-infected patients. Since oxidative stress may have a profound influence on disease progression, fibrosis, and carcinogenesis, our results may meet the aspirations of mandatory introduction of antioxidants as early HCV therapy to counteract ROS consequences.

Ameliorative effects of betaine and ascorbic acid on endocrine and erythrocytic parameters of sexually-maturing female Japanese quails during the dry season.

This study investigated the ameliorative effects of betaine and ascorbic acid on some endocrine and erythrocytic parameters in female Japanese quails (Coturnix coturnix japonica) reared during the dry season. A total of 372 fourteen- day-old female quails sourced commercially was kept in cages for 56 days. After seven days acclimation, all birds were weighed and allotted by complete random design to four groups with 3 replicates per group. Every group having 93 quails, comprised of 31 birds per replicate. Experimental groups were birds fed: Control (basal); ascorbic acid (AA), at 200 mg/Kg; betaine (BET) at 2 g/kg and combination of AA (200 mg/Kg) + BET (2 g/kg) of diets. Daily dry-bulb temperature (DBT), relative humidity (RH) and temperature-humidity index (THI) measured at 08:00 h, 13:00 h and 17:00 h fluctuated widely and exceeded the zone of thermal comfort for Japanese quails. Serum levels of catalase (CAT), reduced glutathione (GSH), cortisol, sex hormones (luteinizing hormone, LH and estradiol) and erythrocyte parameters (packed cell volume, PCV; red blood count, RBC; haemoglobin concentration, Hb; mean corpuscular volume (MCV), hemoglobin (MCH) were obtained at 28, 49 and 70 days of age. In female quails, AA ± BET increased (P < 0.05) CAT and GSH, but decreased (P < 0.05) cortisol levels when compared with control values at varying ages. There were higher (P < 0.05) values of LH in quails fed dietary AA + BET (28 and 49 day-old) and estradiol in those which consumed either BET or AA + BET (28, 49 and 70 day-old) and AA (at 70 day-old). At 49 day-old, either BET or AA + BET increased (P < 0.05) RBC count, but lowered (P < 0.05) MCV and MCH. In conclusion, betaine and ascorbic acid supplementation improved activities of serum sex and stress hormones, and erythrocytic parameters of Japanese quails during the dry season.