Decrease In Superoxide Dismutase Levels Research Articles

Correlation of enhanced oxidative stress with altered thyroid profile: Probable role in spontaneous abortion.

Background:Spontaneous abortion or miscarriage is defined as the loss of a clinically recognized pregnancy that occurs before 20 weeks of gestational age. Changes in thyroid function can impact greatly on reproductive function before, during, and after conception. Oxidative stress affects both implantation and early embryo development by modifying the key of transcription. Malondialdehyde (MDA) is a major breakdown product of split off from lipid peroxidation. Superoxide dismutase (SOD) is responsible for detoxification of superoxide anion and required for normal health and reproduction.Aim:The aim of this study was to define the involvement of thyroid hormones, MDA and SOD levels and to establish MDA levels as an index of lipid peroxidation in women with spontaneous abortion by comparing the results with healthy pregnant females as controls.Materials and Methods:A cross-sectional case-control study was designed with two groups of women with 30 each in healthy pregnancy and with spontaneous abortion.Results:Demographic characteristics such as maternal age, paternal age, gestational age, body mass index, waist-hip ratio as well as biochemical parameters such as blood pressure, hemoglobin (Hb), sugar levels were found to be similar in both the participating groups. Characteristics like gravida and parity were found to be higher in the study group and differ significantly from control group. Spontaneous abortion before 24 weeks of gestational age was found to be associated with significant increase in mean serum thyroid stimulating hormone (TSH) (P = 0.0115) and MDA (P = 0.0001) levels and a significant decrease in mean serum T3 (P = 0.0003) and SOD (P = 0.0005) levels. The linear (Pearson) correlation analysis demonstrated a significant positive correlation of TSH with MDA and negative correlation with SOD in women with spontaneous abortion.Conclusion:The study demonstrates that altered thyroid profile, increased lipid peroxidation in terms of increased MDA levels and decreased SOD levels might be involved in the termination of otherwise wanted pregnancy.

Expression of neutrophil gelatinase-associated lipocalin in low osmolar contrast-induced nephropathy in rats and the effect of N-acetylcysteine.

Serum creatinine (Scr), which is a conventional indicator of contrast-induced nephropathy (CIN), is unable to reflect the damage of kidney promptly. The present study aimed to investigate the value of neutrophil gelatinase-associated lipocalin (NGAL) in kidney and serum of CIN rats to observe whether NGAL can be used as a superior indicator of CIN. Furthermore, N-acetylcysteine (NAC) was used to assess its effect on CIN. A total of 120 adult male Sprague Dawley rats were randomly divided into four groups (n=30/group): CIN rats (CIN), normal rats treated with NAC (NAC), CIN rats treated with NAC (NAC+CIN) and the control group (CON). Serum Scr and NGAL values were measured at 2, 12, 24, 48 and 72 h following the procedure. Immunohistochemistry and western blot analysis were used to detect NGAL within the kidney tissue. Hematoxylin and eosin staining were used to access the renal injury score. Oxidative stress within the kidney was analyzed via malondialdehyde (MDA) and superoxide dismutase (SOD). The level of NGAL in the serum and tissue of the CIN group increased significantly 2 h after the procedure (P<0.05). However, the Scr value did not exhibit a significantly change until 48 h later. Based on the renal injury scores, NAC reduced the kidney damage caused by the contrast. NAC treatment was associated with a decrease in SOD levels and an increase in MDA. These findings suggested that NGAL was a superior indicator of CIN than Scr, as NGAL was able to detect kidney damage much earlier. Furthermore, NAC treatment inhibited oxidative stress, thus protecting against CIN.

Zinc oxide nanoparticles induce renal toxicity through reactive oxygen species

Nanoparticles of zinc oxide (ZnO NPs) are applied in many fields nowadays. Consequently, concerns have been raised about its potential harmful effects. The present study focuses on its toxic effect on podocytes and rats. In vitro study, podocytes were treated with different concentrations of ZnO NPs (10, 50 and 100 μg/ml), the viability of cells was decreased as time prolonged according to MTT assay. Meantime, flow cytometry analysis indicated that ZnO NPs induced intracellular accumulation of reactive oxygen species (ROS) and apoptosis. The measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) showed that ZnO NPs decreased SOD level and increased MDA level. Interestingly, pretreatment with N-mercaptopropionyl-glycine, known as a type of ROS scavenger, could inhibit podocyte apoptosis induced by ZnO NPs. Meantime, a loss of nephrin can be detected, which may result in a direct damage to slit diaphragms. In vivo study, adult male Wistar rats were administrated with 3mg/kg/day ZnO NPs for 5 days, body weight and kidney index were significantly reduced. In addition, ZnO NPs decreased the activity of catalase and SOD in kidney cortex in vivo. It could be concluded that ZnO NPs present toxic effect on podocytes and Wistar rats, which was related with oxidative stress.

Protective effect of combined vitamin C and E against ovarian and endometrial toxicity in rats that receiving oral rhodamine B

This study aimed to investigate whether combined supplementation with vitamin C and vitamin E was able to modify the superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the ovarium of rats exposed to rhodamine B. Twenty-five female Wistar albino rats were divided into five groups (n=5 each), including control (untreated group); rhodamine B group; rhodamine B group which received vitamin C (0.2 mg)+vitamin E (0.04 IU/g body weight); rhodamine B group which received vitamin C (0.4 mg)+vitamin E (0.04 IU/g body weight); and the rhodamine B group which received vitamin C (0.8 mg)+vitamin E (0.04 IU/g body weight). Analysis of MDA levels as a marker of lipid peroxidation was done spectrophotometrically. Analysis of SOD levels was done by enzyme-linked immunosorbent assay technically. Endometrial histology was analyzed in hematoxylin eosin staining. This increase in ovarian MDA was significantly (p<0.05) attenuated by the two highest dose treatments of combined vitamin C and vitamin E. Rhodamine B significantly decreased SOD levels compared to the untreated group. This decrease in ovarian SOD level was significantly attenuated by the second and third doses of the combined vitamin C and vitamin E. The vascular number and gland density were significantly lower in the rhodamine B group compared to the untreated control group (p>0.05). All doses also significantly prevented rhodamine B-induced decrease in the vascular number and gland density. In conclusion, the protective effect of combined vitamin C and vitamin E against ovarian and endometrial toxicity in rats receiving oral rhodamine B is due to inhibition of the lipid peroxidation, modulation of SOD levels, and the endometrium repairing effect.

Effect of methotrexate and doxorubicin cumulative doses on superoxide dismutase levels in childhood acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is the mostcommon malignancy in children. Chemotherapeutic drugs forALL such as methotrexate (Mtx) and doxorubicin producereactive oxygen species (ROS), a type of free radical. The ROScan reduce levels of antioxidants in the body, including superoxidedismutase (SOD). Decreased SOD levels can cause DNA, lipid,and protein damage, which in turn may lead to adverse effectsand treatment failure.Objective To determine the effect of Mtx and doxorubicincumulative doses on SOD levels in children with ALL.Methods We conducted a retrospective cohort study in childrenwith ALL who underwent chemotherapy in Dr. Sardjito Hospitalin October 2011 who had completed the induction phase. Riskfactors for decreased SOD levels were analyzed by Cox regressionand hazard ratio, with a significant level of P &lt;0.05.Results Of 40 patients enrolled, Mtx ≥ 3000 mg/m2 significantlydecreased SOD levels (HR 9.959; 95%CI 2.819 to 35.183; P=0.001). However, doxorubicin ≥90 mg/m2 did not significantlydecrease SOD levels (HR 0.59 95%CI 0.194 to 1.765; P=0.34).Conclusion Methotrexate is associated with decreased SOD levelsin children with ALL. However, doxorubicin is not associated withdecreased SOD levels in the same patient population.

Cognitive enhancing, anti-acetylcholinesterase, and antioxidant properties of Tagetes patula on scopolamine-induced amnesia in mice

Background: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue and loss of neurons with a diminished level of the central cholinergic neurotransmitter acetylcholine. Objective: The present study was performed to examine the effect of ethanolic extract of Tagetes patula (EETP) on cognitive impairment induced by scopolamine, a muscarinic antagonist, in mice. Materials and Methods: Rats were treated with EETP and donepezil for 15 successive days followed by treatment with scopolamine (1 mg/kg) for 3 days. The changes in behavioral, biochemical, and neurotransmitters were assessed in rats. Cognitive functions were assessed using step‐through latency on a passive avoidance apparatus and Morris water maze test. Antioxidants parametes such as superoxide dismutase (SOD), glutathione reductase (GR), lipid peroxidation (LPO), and nitrates were assessed. Neurotransmitters including acetylcholinesterase (AChE), dopamine (DA), and serotonin were also assessed, and neuronal damage was also analyzed. Results: Scopolamine‐treated rats showed impaired learning and memory, increased activity of AChE, LPO and decreased levels of SOD, reduced glutathione, nitrates, serotonin, and DA. The EETP significantly reversed the scopolamine‐induced cognitive impairment in mice was measured by the passive avoidance test. In addition, EETP decreased escape latency in the Morris water maze. In probe trail session, EETP increased the latency time in the target quadrant. Ex vivo EETP inhibited AChE activity in the mice brain. EETP treated mice significantly increased the SOD, GR, nitrates, DA, and serotonin levels, and decreased the level of LPO when compared with scopolamine‐treated mice. Conclusion: These results indicate that EETP may exert anti‐amnesic effect through both by anti‐AChE and antioxidant mechanisms. Key words: Cognition, Morris water maze, passive avoidance, scopolamine, Tagetes patula, transfer latency

Effect of methotrexate and doxorubicin cumulative doses on superoxide dismutase levels in childhood acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is the mostcommon malignancy in children. Chemotherapeutic drugs forALL such as methotrexate (Mtx) and doxorubicin producereactive oxygen species (ROS), a type of free radical. The ROScan reduce levels of antioxidants in the body, including superoxidedismutase (SOD). Decreased SOD levels can cause DNA, lipid,and protein damage, which in turn may lead to adverse effectsand treatment failure.

N-Acetyl Cysteine Inhibits Endothelin-1-Induced ROS Dependent Cardiac Hypertrophy through Superoxide Dismutase Regulation.

Oxidative stress down regulates antioxidant enzymes including superoxide dismutase (SOD) and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine (NAC) can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1)-induced cardiac hypertrophy. In this experimental study at QAU from January, 2013 to March, 2013. ET-1 (50 µg/kg) and NAC (50 mg/kg) were given intraperitoneally to 6-day old neonatal rats in combination or alone. All rats were sacrificed 15 days after the final injection. Histological analysis was carried out to observe the effects caused by both drugs. Reactive oxygen species (ROS) analysis and SOD assay were also carried out. Expression level of hyper- trophic marker, brain natriuretic peptide (BNP), was detected by western blotting. Our findings showed that ET-1-induced cardiac hypertrophy leading towards heart failure was due to the imbalance of different parameters including free radical-induced oxidative stress and antioxidative enzymes such as SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative response associated with hypertrophy. ET-1-induced hypertrophic response is associated with increased ROS production and decreased SOD level, while NAC plays a role against free radicals-induced oxidative stress via SOD regulation.

Effects of Allopurinol and Apocynin on Renal Ischemia-Reperfusion Injury in Rats

BackgroundThis study evaluated the effects of allopurinol (ALP), a xanthine oxidase inhibitor, and apocynin (APC), a NADPH oxidase inhibitor, administered alone or together, on kidney damage caused by renal ischemia-reperfusion (IR) in rats. MethodsThirty rats were randomly assigned to 5 groups. Group 1 was a sham group. Group 2 was the renal IR control group (30-min ischemia followed by 24-h reperfusion). In groups 3 and 4, ALP or APC, respectively, was administered 1 h before the ischemia. In group 5, ALP and APC were co-administered. Blood urea nitrogen (BUN) and serum creatinine (Cr), renal tissue malondialdehyde (MDA) and superoxide dismutase (SOD), and histological changes were evaluated. ResultsA significant increase in BUN and Cr level, and histological damage was seen in the IR control group, indicating renal injury. Elevated MDA and decreased SOD levels in the IR control group demonstrated that renal damage occurred through oxidative stress. Pretreatment with ALP or APC alone or together prevented IR-induced renal damage. However, there was no significant difference between treatment with a single drug and co-administration of ALP and APC. ConclusionsThe use of ALP and/or APC before ischemia may be beneficial to ameliorate renal IR injury.

Isolation of major phenolics from Launaea spinosa and their protective effect on HepG2 cells damaged with t-BHP

Context: Some Launaea species (Asteraceae) are used traditionally to treat liver oxidative stress.Objective: The present study investigates the protective effects of isolated compounds from Launaea spinosa Sch. Bip. (Asteraceae) against oxidative stress on t-BHP-induced HepG2 cells.Materials and methods: Major phenolic content from flowering aerial parts of L. spinosa was isolated and identified. The protective effects of isolated compounds (10 and 20 μM) against oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells were investigated through the measurement of aspartate aminotransferase (AST), alanine transaminase (ALT), and superoxide dismutase (SOD) levels.Results: A new phenolic compound identified as 2,3-diferulyl R,R-(+) methyl tartrate (6), in addition to five known metabolites, esculetin (1), esculetin-7-O-d-glucoside (cichoriin) (2), fertaric acid (3), acacetin-7-O-d-glucoside (4), and acacetin-7-O-d-glucuronic acid (5), were isolated. Oxidant-induced damage by 200 μM t-BHP in HepG2 cells was inhibited by compounds 1, 4, and 5 (10 and 20 μM), or quercetin (10 μM; positive control). The protective effects of compounds 1, 4, and 5 were associated with decreasing in AST, ALT, and SOD levels. Compound 4 (20 μM) decreased the AST level from 128.5 ± 13.9 to 7.9 ±1.8 U/mL. Meanwhile, compound 1 (20 μM) decreased ALT activity from 20.3 ± 7.0 to 7.6 ± 2.4 U/mL, while compound 5 decreased SOD levels from 41.6 ± 9.0 to 28.3 ± 3.4 mU/mg.Conclusion: The major phenolic compounds isolated from L. spinosa displayed a significant cytoprotective effect against oxidative stress, leading to maintenance of the normal redox status of the cell.

Inhibition of endoplasmic reticulum stress by ethyl pyruvate attenuates simulated ischemia reperfusion injury of neonatal rat cardiomyocyte

Objective To explore the effect of ethyl pyruvate(EP)on the simulated ischemia reperfusion(SIR)injury of neonatal rat cardiomyocyteand the role of endoplasmic reticulum stress(ERS)in this procedure. Methods The cultured neonatal rat cardiomyocytes, pretreated with EP(5 or 10 mmol/L)for 2 h, were subjected to SIR injury(hypoxia for 2 h, reoxygenation for 4 h). Methyl thiazolyl tetrazolium (MTT)method was used to detect the cell viability,special kits were used to detected the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in culture medium.Western blotting was used to detect the expression of ERS related molecules glucose regulated protein 78(GRP78) and CCAAT/enhancerbinding protein homologous protein(CHOP).Further, EP treatment was added with the ERS activator thapsigargin(THA), the effect of THA on the protection of EP against SIR was observed. Results Both 5 and 10 mmol/LEP treatment dramatically increased the cell viability(0.424±0.016 and 0.517± 0.020), downregulated the increased MDA level[(16.17±1.75)and(11.45±1.20)μmol/L]and decreased SOD level[(58.61±4.70)and(72.60±4.35) U/L]in the culture medium(vs.the SIR group, P<0.05).Compared with the control group, the level of GRP78 and CHOP increased significantly in the SIR group(P< 0.05), while EP treatment significantly decreased the level of GRP78 and CHOP(vs.the SIR group, P<0.05).Further, the ERSactivator THA reversed the protection of EP, decreased the cell viability(vs.the EP+ SIR group, P< 0.05), upreguleted the expression of GRP78 and CHOP(vs.the EP+ SIR group, P<0.05). Conclusion EP treatment can protect against SIR injury of neonatal rat cardiomyocyte, this effect is associated with inhibition of ERS. Key words: Ethyl pyruvate; Cardiomyocyte; Simulated ischemia reperfusion; Endoplasmic reticulum stress

Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats

The aim of the current study was to investigate the probable protective effects of Pentoxifylline (PTX) and Alpha Lipoic Acid (ALA), which display anti-oxidative efficacy against hepatotoxicity and nephrotoxicity, those being the major side effects of Methotrexate (MTX). Rats were divided into four groups: a control group; MTX (20mg/kg/day) group; MTX+PTX (20mg/kg/day+50mg/kg/day) group; and an MTX+ALA (20mg/kg/day+100mg/kg/day) group. At the end of the experiment, biochemical, histochemical and immunohistochemical analyses were performed on liver and kidney tissues of rats. We determined Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA), Nitric Oxide (NO) and Xanthine Oxidase (XO) levels in the liver and kidney. Moreover, Gamma Glutamyl Transferase (GGT), Direct Bilirubin (DBil), Blood Urea Nitrogen (BUN), and urea levels were measured in the serum. The histochemical evaluation revealed a significant decrease in MTX caused damage in the PTX- and ALA-treated groups (especially in ALA group). On the other hand, the immune staining of iNOS and TNF-α were observed most densely in the MTX group, while the density decreased in the PTX- and ALA-administered groups. We determined increased GGT, BUN, urea and levels of CAT, MDA, NO, and XO values in both groups, while GSH-Px (an increase in liver tissue) and DBil levels were decreased in the group that received MTX. However, we determined decreased SOD levels in liver tissue. In the PTX and ALA groups, the levels of GGT, BUN and urea as well as the levels of CAT, MDA, NO and XO decreased (SOD increased in the liver tissue), and the levels of GSH-Px and DBil increased. In conclusion, it can be stated that, although ALA is more effective in preventing the toxic effects of MTX on the liver and kidney, PTX also has a preventive effect. As a result, we can readily suggest that ALA and PTX can have protective effects by decreasing MDA, NO, BUN and urea values as antioxidants against MTX-induced damage in liver and kidney of rats.

Ischemic preconditioning increases GSK-3β/β-catenin levels and ameliorates liver ischemia/reperfusion injury in rats.

Ischemic preconditioning (IPC) ameliorates ischemia/reperfusion (I/R) injury in a number of organs, and the glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway regulates I/R-induced proliferation and apoptosis in the central nervous system and heart. However, the function of this signaling pathway in IPC during liver I/R remains unclear. Thus, in this study, we aimed to investigte the role of the GSK-3β/β-catenin pathway during I/R and following ischemic preconditioning. For this purpose, 30 Sprague-Dawley rats were randomly divided into the sham-operated, the I/R and the IPC groups (n=10). Following reperfusion, liver pathology, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), maleic dialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed. Western blot analysis was performed to quantify the GSK-3β, Ser9-phospho-GSK-3β (p-GSK-3β), cytosolic and nuclear β-catenin, vascular endothelial growth factor (VEGF), Bcl-2 and survivin levels. In addition, the Bcl-2 and survivin mRNA levels were assessed by RT-qPCR. Compared with the sham-operated group, I/R increased serum ALT, AST and MDA activity and decreased SOD levels, while IPC significantly decreased serum ALT, AST and MDA activity and increased SOD levels, compared with the I/R group. Simultaneously, I/R increased p-GSK-3β protein expression, and decreased Bcl-2 and survivin protein and mRNA levels. IPC further increased the protein expression of p-GSK-3β, and also increased cytosolic and nuclear β-catenin and VEGF expression compared with the I/R group; the expression of Bcl-2 and survivin was also increased by IPC, both at the mRNA and protein level. The total GSK-3β expression remained unaltered in all the groups. In conclusion, our data demonstrate that IPC exerts protective effects against liver injury induced by I/R and activates the GSK-3β/β-catenin signaling pathway.

Detection and Quantification of Free Radicals in Peroxisomal Disorders: A Comparative Study with Oxidative Stress Parameters.

Free radicals have been thought to participate in pathogenesis of peroxisomal disorders. The aim of the work is to detect free oxide radicals in blood of patients with peroxisomal disorders and to study their relation with various oxidative stress parameters. Twenty patients with peroxisomal disorders and 14 age and sex matched healthy subjects were included in the study. Patients with peroxisomal disorders were subdivided according to diagnosis into peroxisomal biogenesis disorders and single enzyme deficiency. Oxidative stress was evaluated in both patients and control subjects by assessment of free radicals, malondialdehyde, nitric oxide metabolites and superoxide dismutase. There was increase in free radicals, malondialdehyde, nitric oxide metabolites in patients compared with control subjects. However, there was decrease in superoxide dismutase levels in patients compared with control subjects. We concluded that there is excess free radicals production accompanied with decrease in antioxidant defenses in patients with peroxisomal disorders. These results strongly support a role of free radicals in the pathophysiology of peroxisomal disorders and strengthen the importance of oxidative stress phenomenon in peroxisomal disorders pathogenesis.

The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

Methotrexate (MTX), used commonly as an antimetabolite drug in cancer therapy, leads to acute toxic side effects in tissues or organs containing rapidly dividing cells, such as bone marrow, gastrointestinal mucosa, and seminiferous tubules. In this study, we investigated the protective effects of vitamin E and L-carnitine against MTX-induced injury in rat testis. Rats were divided into 4 groups, including the control group. The study took 17 days and the animals received daily doses of 0.5 mL/kg saline, 250 mg/kg vitamin E, or 500 mg/kg L-carnitine intraperitoneally. The experimental groups received 20 mg/kg methotrexate intraperitoneally on days 3 and 10. Weight loss, testicular weight loss and marked histological injuries, increased malondialdehyde levels, and decreased superoxide dismutase levels were only observed in the MTX-treated groups. Vitamin E and L-carnitine treatments did not affect MTX-induced weight loss or testicular weight loss, but they inhibited MTX-induced testicular histological injuries. Vitamin E and L-carnitine treatments suppressed the increases in malondialdehyde levels and the decreases in superoxide dismutase levels. Vitamin E and L-carnitine treatments decreased MTX-induced testicular histological injuries, and these results were supported by biochemical measurements.

Impact of Co-administered Lopinavir/Ritonavir and Sulfamethoxazole/Trimethoprim on Reproductive Indices of Male Albino Rats

Antiretroviral drugs containing Lopinavir/ ritonavir (LPV/r) are usually co-administered with sulfamethoxazole / trimethoprim (SMX/TMP) in the management of HIV/AIDS and co infections. The concurrent use of these drugs may place more adverse burden on testicular function because reports have associated these drugs individually with decreased testicular function. This study therefore evaluated the effects of the co-administration of SMX/TMP + LPV/r on reproductive indices of male albino rats. Eighty (80) adult male rats which were divided into five (5) groups A-E were used in this study. Animals in group A which served as the control were treated with 1% ethanol while animals in groups B-E were treated orally with SMX/TMP, (22.4/4.6mg/kg), LPV/r (22.8/5.8mg/kg) and combined doses of SMX/TMP + LPV/r for 2-8 weeks respectively. Animals were sacrificed at the end of treatment, testes were collected and weighed. Sperm count, sperm motility, and morphology were evaluated. Testicular levels of malondialdehyde (MDA), super oxide dismutase (SOD) and histopathological changes were also analyzed. Single doses of LPV/r and SMX/TMP produced significant time dependent decrease in total sperm count and sperm motility, with increase in abnormal sperm morphology. Treatment with single doses of these agents time dependently increased testicular MDA, decreased SOD level and induced abnormal testicular histopathological changes. No significant synergistic effects were observed in all evaluated parameters when these agents were co-administered. Conclusion: Due to lack of significant synergistic effects on all evaluated parameters with the co-administration of these agents, the concurrent use of these agents in the management of HIV and co- infections may not have any deleterious effect on male reproductive function.

Investigation of fine chalk dust particles’ chemical compositions and toxicities on alveolar macrophages in vitro

The aim of the study is to investigate chemical compositions of fine chalk dust particles (chalk PM2.5) and examine their adverse effects on alveolar macrophages (AMs) in vitro. Morphologies and element concentrations of individual chalk particles were analyzed by using the quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA). The oxidative response of AMs and the potential to generate nitric oxide (NO) by luminol-dependent chemiluminescence (CL) and nitrate reductase method were assessed 4h following the treatment of AMs with differing dosages of fine chalk particles, respectively. Oxidative stress and cytotoxicity elicited by chalk PM2.5 were also examined. The results showed that fine chalk particles were mainly composed of gypsum, calcite, dolomite and a little amount of organic adhesives. Exposure to chalk PM2.5 at 100μgmL−1 or 300μgmL−1 significantly increased intracellular catalase, malondialdehyde, and NO levels and decreased superoxide dismutase level in AMs, leading to leakage of lactate dehydrogenase (LDH) and reduction of the cell viability. Furthermore, luminol-dependent CL from respiratory burst in AMs was enhanced. It was suggested that chalk PM2.5 could make oxidative damages on AMs and result in cytotoxicity, being likely attributed to excessive reactive oxygen species or reactive nitrogen species induced by mixture of fine gypsum and calcite/dolomite particles.

Protective Effects of Combined Therapy of Rutin with Silymarin on Experimentally-Induced Diabetic Neuropathy in Rats

The management of diabetic neuropathy (DN) is still a challenge for physicians. Hyperglycemia induced oxidative stress involves in the development of diabetic neuropathy, which could be reversed by supplementation of antioxidants. In the present study, it has targeted the oxidative stress mediated nerve damage in DN by using combined therapy of rutin (RT) and silymarin (SM). Diabetes was induced by single streptozotocin (STZ, 65 mg/kg i.p.) injection. The diabetic rats were treated daily with RT (100 mg/kg), SM (60 mg/kg) and RT (50 mg/kg) + SM (30 mg/kg) for 6 consecutive weeks. Pain-related behavior tests were performed including tail flick, paw-pressure analgesia and Rota-rod treadmill performance. Serum glucose, insulin, tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and interleukine-1β (IL-β) levels were estimated. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) were measured. Diabetic rats that developed neuropathy were revealed by decreased tail-flick latency, paw-withdrawal latency and motor coordination. RT (100 mg/kg/day) and SM (60 mg/kg/day) dosed to diabetic rats, ameliorated hyperalgesia, analgesia and led to improved motor coordination. However, the combined therapy of RT (50 mg/kg/day) with SM (30 mg/kg/day) showed more significant effects in these parameters. STZ significantly increased TBARS and decreased GSH levels in sciatic nerve whereas combined therapy of RT and SM produced higher significant protection compared to individual. Similarly, combined therapy showed more significant amelioration in decreased levels of SOD, CAT, GST, GS and GPx activities in sciatic nerve of diabetic rats. Present results concluded that the combined therapy of phenolic compounds such as RT and SM had higher protective effects than their individual supplementations against DM.

Hepatoprotective Effect of Manganese Chloride Against CCl4-Induced Liver Injury in Rats

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl4)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl4-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl4 increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl4 intoxication alone. Thus, the histopathological studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl4-induced oxidative liver damage.

Effects of compound traditional Astragalus and Salvia Miltiorrhiza extract on acute and chronic hepatic injury

Previous reports showed that Compound Astragalus and Salvia miltiorrhiza extract (CASE), which was mainly composed of astragalosides, astragalus polysaccharide and salvianolic acids, inhibited hepatic fibrosis by mediating transforming growth factor-<TEX>${\beta}$</TEX> (TGF-<TEX>${\beta}$</TEX>)/Smad signaling. Our aim was to examine the effects of CASE on D-galactosamine (D-GalN) treated liver injury in mice and carbon tetrachloride (<TEX>$CCl_4$</TEX>)-induced liver fibrosis in rats. CASE was administered to mice with D-GalN-induced liver injury and to rats with <TEX>$CCl_4$</TEX>-induced liver fibrosis, respectively. Liver injury was routinely evaluated by relative liver weight, serum levels of ALT, AST, hyaluronic acid (HA), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, hydroxyproline (HYP) and histopathologic changes. Treatment of mice with CASE (60, 120, and 240 mg/kg, ig) significantly lowered ALT, relative liver weight, and MDA levels when compared with D-GalN treated mice. CASE (120, 240 mg/kg) significantly lowered ALT, AST, HA, HYP, and MDA levels against <TEX>$CCl_4$</TEX> treated rats. Decreased SOD level was reversed with CASE treatment. Upon histopathological examination, CASE treatment had significantly inhibitory effect on the progression of hepatic fibrosis in rats. These results indicate that CASE might be effective in treatment and prevention of acute and chronic hepatic injury due to its antioxidant activity.