Ming Yie Liu

Effects of vitamin E and/or C on reactive oxygen species-related lead toxicity in the rat sperm

This study was undertaken to investigate whether treatment with vitamin E (VE) and/or vitamin C (VC) protects rat sperm by inhibiting reactive oxygen species generation induced by lead (Pb) exposure. Male Sprague-Dawley rats were assigned to the following five groups: vitamin-unsupplemented; 150 mg VE/kg chow supplemented; 300 mg VE/kg chow supplemented; 500 mg VC/l drinking water supplemented and 150 mg VE/kg chow + 500 mg VC/l drinking water supplemented group. Rats in each group were divided into Pb-unexposed and Pb-exposed subgroups, received weekly intraperitoneal injection of 10 mg sodium acetate or 10 mg Pb acetate/kg for 6 weeks, respectively. The blood and sperm Pb levels were analyzed by graphite furnace atomic absorption spectrophotometer. Chemiluminescence was measured to evaluate the generation of sperm reactive oxygen species (ROS). Motility and sperm-oocyte penetration rate (SOPR) were measured. In Pb-unexposed rats, epididymal sperm counts, motility, ROS, and SOPR were not different in the five supplemented groups. Lead exposure might decrease the defense capacity of sperm to the oxidative stress and therefore elevate the ROS generation, reduce sperm motility, and reduce SOPR. Supplementation with VE and/or VC reduced ROS generation, prevented loss of motility and capacity of oocyte penetration in Pb-exposed rats. This study suggests that supplementation with VE and/or VC inhibits Pb-related ROS generation, protects spermatozoa from loss of motility and oocyte penetration capability.

Lead exposure causes generation of reactive oxygen species and functional impairment in rat sperm

The relationships between blood lead, sperm lead, sperm reactive oxygen species (ROS) level, and sperm fertile capability were investigated to understand the effects of lead exposure on sperm function and the mechanism of these effects. Male Sprague-Dawley rats, 7 weeks old, were randomly divided into control group and lead-treated group. The controls and lead-treated animals received intraperitoneal injection of 10 mg sodium acetate and 10 mg lead acetate/kg body weight, respectively, weekly for 6 or 9 weeks. The blood lead and epididymal sperm lead were analyzed by graphite furnace atomic absorption spectrophotometer. Chemiluminescence was measured to evaluate the generation of sperm ROS. Sperm-oocyte penetration rate (SOPR) was measured to evaluate sperm function. After 6 weeks of lead exposure, the rats had average blood lead levels of 32 microg/dl, sperm lead levels of 0.67 +/- 0.11 microg/10(9) sperm, unchanged epididymal sperm counts, percent of motile sperms, and motile epididymal sperm counts compared with control animals. However, after 9 weeks of lead exposure, the rats had average blood lead levels of 48.0 +/- 4.3 microg/dl, sperm lead levels of 0.88 +/- 0.16 microg/10(9) sperm, statistically lower epididymal sperm counts, and lower motile epididymal sperm counts. There was a good correlation between the blood lead and sperm lead(r2 = 0.946, P < 0.001). The sperms of lead-exposed rats produced significantly higher counts ofchemiluminescence than did those from the control rats (P < 0.001). The chemiluminescence counts were positively associated with sperm lead level (r2 = 0.613, P < 0.001). Epididymal sperm counts, motility and motile epididymal sperm counts were negatively associated with sperm chemiluminescence (r2 = 0.255, 0.152, and 0.299; P < 0.01, 0.05, and 0.01, respectively). The SOPR were positively associated with epididymal sperm counts, motility and motile epididymal sperm counts (r2 = 0.136, 0.285, and 0.264; P < 0.05, 0.01, and 0.001, respectively). The sperm chemiluminescence was negatively associated with SOPR (r2 = 0.519, P < 0.001). It is concluded that lead exposure probably affected the sperm function by activating one of the pathways of ROS generation.

Phosphine-induced oxidative damage in rats: role of glutathione

Phosphine (PH(3)), generated from aluminium, magnesium and zinc phosphide, is a widely used pesticide. PH(3) induces oxidative stress in insects, mammalian cells, animals, and humans. The involvement of glutathione (GSH) in PH(3)-induced oxidative toxicity is controversial. GSH levels in various tested tissues were reduced in aluminium phosphide-poisoned rats and humans, while the levels remained unchanged in insects and mammalian cells. This study examines the effectiveness of endogenous GSH as a protective agent against PH(3)-induced oxidative damage in rats. The association of PH(3)-induced nephrotoxicity and cardiotoxicity with free radical production was also tested. Male Wistar rats, administered intraperitoneally (I.P.) with PH(3) at 4 mg/kg, were evaluated 30 min after treatment for PH(3) toxicity to organs. PH(3) significantly decreased GSH, GSH peroxidase and catalase, while significantly increased lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals), DNA oxidation (as 8-hydroxydeoxyguaonsoine) and superoxide dismutase (SOD) levels in kidney and heart. These changes were significantly alleviated by melatonin (10 mg/kg I.P., 30 min before PH(3)), with the exception of SOD activity in heart tissue. The study also found that buthionine sulfoximine (1 g/kg I.P., 24 h before PH(3)) significantly enhanced the effect of PH(3) on GSH loss and lipid peroxidation elevation in lung. These findings indicate that (1) endogenous GSH plays a crucial role as a protective factor in modulating PH(3)-induced oxidative damage, and (2) PH(3) could injure kidney and heart (as noted earlier with brain, liver and lung) via oxidative stress and the antioxidant melatonin effectively prevents the damage.

LEAD-INDUCED CHANGES IN SPERMATOZOA FUNCTION AND METABOLISM

The relationships between sperm reactive oxygen species (ROS) generation, the capacitation process and acrosome reaction, and the spermoocyte penetration rate (SOPR) were investigated to understand the effect of lead toxicity on sperm functions and the mechanisms of these effects. Male Sprague-Dawley rats received weekly intraperitoneal injections of 20 mg or 50 mg lead acetate/kg or 20 mg or 50 mg sodium acetate/kg (control) for 6 wk. Serum testosterone was measured by radioimmunoassay. In cauda epididymal spermatozoa, the chemiluminescence was measured to evaluate the sperm ROS generation. Chlortetracycline fluorescence assay was used to study the status of capacitation and acrosome reaction on fresh cauda epididymal spermatozoa and after 2, 4, or 24 h of incubation with 5 mg/ml bovine serum albumin. In lead-exposed rats, the serum testosterone levels were reduced, and the percentage of capacitation and the chemiluminescence were significantly increased in fresh cauda epididymal spermatozoa. The serum testosterone levels were negatively associated with the percentage of acrosome-reacted spermatozoa. Sperm chemiluminescence was positively correlated with the percentage of both capacitated and acrosome-reacted spermatozoa. The SOPR was negatively associated with the percentage of both capacitated and acrosome-reacted spermatozoa. In summary, this study showed that male rats exposed to lead had decreased serum testosterone levels and that this metal produced early onset of capacitation by one of the pathways of ROS generation. These effects might consequently result in premature acrosome reaction and reduced zona-intact oocyte-penetrating capability.

Sesamol delays mortality and attenuates hepatic injury after cecal ligation and puncture in rats: role of oxidative stress.

ABSTRACT Sesame oil potently protects rats against sepsis, and sesamol appears to be the protective ingredient in sesame oil. The aims of the present study were to examine the effects of sesamol on mortality and reactive oxygen species-associated liver injury in Wistar rats with cecal-ligation-and-puncture-induced sepsis (septic rats). After sepsis was induced, sesamol was administered every 6 h. The survival rate was determined during the ensuing 48 h. Hepatic injury was assessed using blood biochemistry and histological examination. Hepatic oxidative stress was assessed by determining the levels of liver lipid peroxidation, hydroxyl radical, and superoxide anion generation, and nitric oxide production 12 h after cecal ligation and puncture. Inducible nitric oxide synthase expression was also determined. Sesamol delayed mortality and attenuated hepatic injury in septic rats. Hepatic lipid peroxidation, hydroxyl radical, and superoxide anion levels were significantly lower in sesamol-treated septic rats. Furthermore, sesamol inhibited the production of nitrite and the expression of inducible nitric oxide synthase in the liver in septic rats. Therefore, sesamol may delay mortality and attenuate oxidative stress-associated liver injury by inhibiting the production of nitric oxide, at least partially, in septic rats.

Effect of sesame oil on oxidative-stress-associated renal injury in endotoxemic rats : Involvement of nitric oxide and proinflammatory cytokines

This study aimed to investigate the effect of sesame oil on oxidative stress-associated renal injury induced by lipopolysaccharide in rats. The effects of sesame oil on renal injury, oxidative stress, hydroxyl radical, superoxide anion, nitric oxide, and proinflammatory cytokines were assessed after a lipopolysaccharide challenge. Sesame oil attenuated lipopolysaccharide-induced renal injury, decreased lipid peroxidation, increased the activities of superoxide dismutase, catalase, and glutathione peroxidase, reduced hydroxyl radical generation and nitric oxide production, and had no effect on superoxide anion generation in lipopolysaccharide-challenged rats. In addition, sesame oil significantly decreased tumor necrosis factor-α and interleukin 1β production 1 and 6 h, respectively, after lipopolysaccharide administration in mice. Thus, sesame oil attenuates oxidative stress-associated renal injury via reduction of the production of nitric oxide and the generation of proinflammatory cytokines in endotoxemic rats.

Sesame oil attenuates multiple organ failure and increases survival rate during endotoxemia in rats.

ObjectiveTo investigate the effects and the possible mechanism of sesame oil on multiple organ failure induced by lipopolysaccharide in rats. DesignLaboratory in vivo study of the effects of sesame oil on serum aspartate aminotransferase, &ggr;-glutamyltransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, lipid peroxide, and nitric oxide concentrations. To assess the effect of sesame oil on xanthine oxidase, serum uric acid was measured. Furthermore, lipid peroxide concentrations in liver and kidney were determined. SettingUniversity laboratory. SubjectsMale Wistar rats. InterventionsBlood testing. Measurement and Main ResultsSerum aspartate aminotransferase, &ggr;-glutamyltransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, and uric acid concentrations were determined. Lipid peroxide was analyzed by using a commercial kit. Nitric oxide production was estimated by Griess reaction. Sesame oil ameliorated hepatic and renal damage in a dose-dependent manner and increased animal survival in lipopolysaccharide-treated rats. Sesame oil decreased lipid peroxide concentration in serum but not in liver and kidney. Serum nitrite production was unaffected by sesame oil ingestion. Furthermore, the activity of xanthine oxidase was reduced by sesame oil in lipopolysaccharide-challenged rats. ConclusionSesame oil ameliorated multiple organ failure and mortality via its inhibition of xanthine oxidase in lipopolysaccharide-dosed rats. Xanthine oxidase may play a critical role in sesame oil-associated organ protection during endotoxemia in rats.

Attenuation of endotoxin-induced oxidative stress and multiple organ injury by 3,4-methylenedioxyphenol in rats

ABSTRACT Endotoxin is a potent inducer of lipid peroxidation (LPO), which is associated with the development of endotoxemia. 3,4-Methylenedioxyphenol (sesamol) is one of the sesame oil lignans with a high anti-LPO effect. Whether sesamol can attenuate endotoxin-induced LPO and multiple organ injury is unknown. After a dose response for sesamol in endotoxin-challenged rats was established, experiments were conducted to assess its effects on hydroxyl radical, peroxynitrite, and superoxide anion counts, activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as the production of nitric oxide (NO) and the expression of inducible NO synthase. In addition, the effects of sesamol on endotoxin-induced hepatic and renal injuries were assessed. Sesamol (a) dose dependently reduced serum LPO inendotoxin-challenged rats, (b) decreased hydroxyl radical and peroxynitrite, but not superoxide anion counts, (c)increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in endotoxin-treated rats, (d)reduced NO production and inducible NO synthase expression, and (e) attenuated hepatic and renal injuries induced by endotoxin in rats. We concluded that sesamol might protect against organ injury by decreasing NO-associated LPO in endotoxemic rats.

The effect of sesamol on systemic oxidative stress and hepatic dysfunction in acutely iron-intoxicated mice.

This study investigated the effect of sesamol (3,4-methylenedioxyphenol) on systemic oxidative stress and hepatic function in acutely iron-intoxicated mice. Sesamol reduced the levels of lipid peroxidation, hydroxyl radical, iron production and superoxide anion generation, and xanthine oxidase activity in iron-intoxicated mice. In addition, sesamol decreased the serum levels of aspartate aminotransferase and alanine aminotransferase, and ameliorated iron-intoxication-induced histological changes in the liver. In summary, sesamol might attenuate systemic oxidative stress by reducing xanthine oxidase and improving hepatic function in iron-intoxicated mice.

Sesame oil protects against lipopolysaccharide-stimulated oxidative stress in rats

ObjectiveThe aim of this study was to determine the effects and the defense mechanisms of sesame oil on lipopolysaccharide-induced oxidative stress in rats. DesignLaboratory in vivo study of the effect of sesame oil on lipid peroxide, superoxide anion, superoxide dismutase, catalase, glutathione, and nitrite concentrations. To assess the effect of sesame oil on hepatic function, we determined serum aspartate aminotransferase, total bilirubin, and liver histology. SettingUniversity laboratory. SubjectsMale SPF Wistar rats. InterventionsBlood testing, administration of oils, and liver biopsies. Measurements and Main ResultsOxidative stress induced by lipopolysaccharide (5 mg/kg, intraperitoneally) was assessed by determination of lipid peroxidation. Sesame oil was given orally immediately after lipopolysaccharide administration, and lipid peroxidation concentrations were determined. The reactive oxygen species superoxide anion was measured by chemiluminescence analyzer. The enzyme activities of superoxide dismutase and catalase and the concentrations of glutathione and nitrite also were determined. Hepatic injury was evaluated by determining the concentrations of serum aspartate aminotransferase and total bilirubin and by liver histologic examination. Sesame oil significantly reduced lipid peroxidation but failed to affect nitrite concentrations in lipopolysaccharide-treated rats. Superoxide anion counts were decreased, and glutathione, but not superoxide dismutase or catalase, was increased in sesame oil-treated groups with lipopolysaccharide-induced oxidative stress. Only sesame oil-treated groups, but not corn oil- or mineral oil-treated groups, showed attenuated hepatic disorder induced by lipopolysaccharide. In addition, sesame oil given 6 hrs after lipopolysaccharide also attenuated lipid peroxidation and hepatic disorder. Furthermore, sesame oil given immediately or 6 hrs after lipopolysaccharide administration significantly reduced morphologic changes induced by lipopolysaccharide. ConclusionA single dose of sesame oil may attenuate oxidative stress and subsequently relieve hepatic disorder in endotoxemic rats.