Weiping Zhao

Bio: Weiping Zhao is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Oxidative stress & DNA damage. The author has an hindex of 8, co-authored 13 publications receiving 179 citations.

Ginsenoside Re promotes human sperm capacitation through nitric oxide-dependent pathway.

Abstract: The regulation of sperm capaci- tation is important for successful fertilization. Ginseno- sides, the biologically effective components of ginseng, have been found to enhance intracellular nitric oxide (NO) production and the latter has recently been indicated to play a significant role in modulation of sperm functions. We investigated the effect of Ginseno- side Re on human sperm capacitation in vitro and the mechanism by which the Ginsenosides play their roles. Spermatozoa were separated by Percoll and incubated with 0, 1, 10, or 100 mM of Ginsenoside Re. The percentages of spontaneous and lysophosphatidylcho- line (LPC)-induced acrosome reaction (AR), as a measure of sperm capacitation, were assayed with fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA). The intracellular cGMP level was measured by ( 3 H) cGMP radioimmunoassay system. The results showed that the percentages of both spontaneous and LPC-induced AR and intracel- lular cGMP level were significantly enhanced by Ginsenoside Re with a concentration-dependent man- ner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside Re. And pretreatment with a NOS inhibitor N o -nitro-L-arginine methyl ester (L-NAME, 100 mM) or a NO scavenger N-acetyl-L-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside Re. Furthermore, the AR- inducing effect of Ginsenoside Re was significantly reduced in the presence of the soluble guanylate cyclase inhibitor LY83583 or cGMP-dependent protein kinase (PCK) inhibitor KT5823, whereas addition of the cGMP analogue 8-Br-cGMP significantly increased the AR of human spermatozoa. Data suggested that Ginsenoside Re is beneficial to sperm capacitation and AR, and that the effect is accomplished through NO/ cGMP/PKG pathway. Mol. Reprod. Dev. 74: 497- 501, 2007. 2006 Wiley-Liss, Inc.

Exogenous melatonin modulates apoptosis in the mouse brain induced by high‐LET carbon ion irradiation

Abstract: The aim of this study was to investigate whether melatonin, a free radical scavenger and a general antioxidant, regulates the brain cell apoptosis caused by carbon ions in mice at the level of signal transduction pathway Young Kun-Ming mice were divided into five groups: control group, irradiation group and three melatonin (1, 5, and 10 mg/kg daily for 5 days ip) plus irradiation-treated groups An acute study was carried out to determine oxidative status, apoptotic cells, and mitochondrial membrane potential (ΔΨm) as well as pro- and anti-apoptotic protein levels in a mouse brain 12 hr after irradiation with a single dose of 4 Gy In irradiated mice, a significant rise in oxidative stress and apoptosis (TUNEL positive) was accompanied by activated expression of Bax, cytochrome c, caspase-3, and decreased ΔΨm level Melatonin supplementation was better able to reduce irradiation-induced oxidative damage marked by carbonyl or malondialdehyde content, and stimulate the antioxidant enzyme activities (superoxide dismutase and catalase) together with total antioxidant capacity Moreover, administration with melatonin pronouncedly elevated the expression of Nrf2 which regulates redox balance and stress Furthermore, melatonin treatment mitigated apoptotic rate, maintained ΔΨm, diminished cytochrome c release from mitochondria, down-regulated Bax/Bcl-2 ratio and caspase-3 levels, and consequently inhibited the important steps of irradiation-induced activation of mitochondrial pathway of apoptosis Thus, we propose that the anti-apoptotic action with the alterations in apoptosis regulator provided by melatonin may be responsible at least in part for its antioxidant effect by the abolishing of carbon ion–induced oxidative stress along with increasing Nrf2 expression and antioxidant enzyme activity

Melatonin modulates acute testicular damage induced by carbon ions in mice

Abstract: The present study was performed to obtain evidence of the radioprotective function of melatonin at different administration levels on carbon ion-induced mouse testicular damage. Outbred Kun-Ming strain mice were divided into six groups, each composed of eight animals: control group, melatonin alone group, irradiation group and three melatonin plus irradiation-treated groups. An acute study was carried out to determine alterations in DNA-single strand break, cell apoptosis, and oxidative stress parameters as well as histopathology in mouse testis 24 h after whole-body irradiation with a single dose of 4 Gy. The results showed that pre-treatment and post-treatment with high-dose melatonin (10 mg/kg) both significantly alleviated carbon ion-induced acute testicular damage, a greater radioprotective effect being observed in the pre-treatment group. On the other hand, low-dose melatonin (1 mg/kg) had a limited radioprotective effect on irradiation-induced degeneration and DNA lesions in mouse testis. Taken together, the data suggest that prophylactic treatment with a higher dose of melatonin is probably advisable to protect against the effects of heavy-ion irradiation.

Effects of carbon ion beam irradiation on lung injury and pulmonary fibrosis in mice

Abstract: Radiation-induced lung injury is a well-described complication of nuclear accidents, marrow-transplant pretreatment and thoracic radiotherapy. The mechanism is complex and no special therapy for it is available at present. To study radiation pulmonary injury following heavy ion radiotherapy for thoracic tumors, Kunming mice were randomly divided into 4 groups: normal control and 2, 4 and 6 Gy irradiation groups which underwent whole-body exposure to 235 MeV/u (12)C(6+) administered at the Heavy Ion Research Facility in Lanzhou (HIRFL). The pathological changes were observed by hematoxylin and eosin staining and the hydroxyproline (HP) content was assessed by spectrophotometry at months 1, 2, 3, 4, 5 and 6 after radiation exposure. In addition, the expression of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β in the lung tissues was measured. The results showed that, compared with the control group, the lung tissue HP content was increased following irradiation but did not statistically significantly change after 4 months in the 4- and 6-Gy-treated groups. However, in the 2-Gy-treated group, the HP content was markedly increased between months 1 and 4 and decreased after month 4. The extent of the lung injury was significantly increased by the higher radiation dosages but was relieved in the 2 Gy group as the time since irradiation increased. The results also revealed that the levels of TNF-α were upregulated and reached a maximum at month 2, but decreased noticeably 2 months later in the experimental groups. The expression of TGF-β increased markedly in month 4 and was altered little in the 4- and 6-Gy-treated groups but decreased sharply in the 2 Gy irradiation group after month 4. These findings suggest that heavy ion radiotherapy for chest tumors causes lung injury to a certain extent, while there is likely to be little injury to lungs treated with <2 Gy, which provides scientific evidence for the use of heavy ion therapy for thoracic tumors.

Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin's primary function and evolution in eukaryotes

Abstract: Mitochondria and chloroplasts are major sources of free radical generation in living organisms. Because of this, these organelles require strong protection from free radicals and associated oxidative stress. Melatonin is a potent free radical scavenger and antioxidant. It meets the criteria as a mitochondrial and chloroplast antioxidant. Evidence has emerged to show that both mitochondria and chloroplasts may have the capacity to synthesize and metabolize melatonin. The activity of arylalkylamine N-acetyltransferase (AANAT), the reported rate-limiting enzyme in melatonin synthesis, has been identified in mitochondria, and high levels of melatonin have also been found in this organelle. From an evolutionary point of view, the precursor of mitochondria probably is the purple nonsulfur bacterium, particularly, Rhodospirillum rubrum, and chloroplasts are probably the descendents of cyanobacteria. These bacterial species were endosymbionts of host proto-eukaryotes and gradually transformed into cellular organelles, that is, mitochondria and chloroplasts, respectively, thereby giving rise to eukaryotic cells. Of special importance, both purple nonsulfur bacteria (R. rubrum) and cyanobacteria synthesize melatonin. The enzyme activities required for melatonin synthesis have also been detected in these primitive species. It is our hypothesis that mitochondria and chloroplasts are the original sites of melatonin synthesis in the early stage of endosymbiotic organisms; this synthetic capacity was carried into host eukaryotes by the above-mentioned bacteria. Moreover, their melatonin biosynthetic capacities have been preserved during evolution. In most, if not in all cells, mitochondria and chloroplasts may continue to be the primary sites of melatonin generation. Melatonin production in other cellular compartments may have derived from mitochondria and chloroplasts. On the basis of this hypothesis, it is also possible to explain why plants typically have higher melatonin levels than do animals. In plants, both chloroplasts and mitochondria likely synthesize melatonin, while animal cells contain only mitochondria. The high levels of melatonin produced by mitochondria and chloroplasts are used to protect these important cellular organelles against oxidative stress and preserve their physiological functions. The superior beneficial effects of melatonin in both mitochondria and chloroplasts have been frequently reported.

Mutation research/fundamental and molecular mechanisms of mutagenesis: special issue: DNA repair and genetic instability.

Abstract: Ionizing radiation (IR) induces DNA strand breaks leading to cell death or deleterious genome rearrangements. In the present study, we examined the role of N-acetyl-L-cysteine (NAC), a clinically proven safe agent, for it’s ability to protect against -ray-induced DNA strand breaks and/or DNA deletions in yeast andmammals. In the yeast Saccharomyces cerevisiae, DNA deletions were scored by reversion to histidine prototrophy. Human lymphoblastoid cells were examined for the frequency of -H2AX foci formation, indicative of DNA double strand break formation. DNA strand breaks were also measured in mouse peripheral blood by the alkaline comet assay. In yeast, NAC reduced the frequency of IR-induced DNA deletions. However, NAC did not protect against cell death. NAC also reduced -H2AX foci formation in human lymphoblastoid cells but had no protective effect in the colony survival assay. NAC administration via drinking water fully protected against DNA strand breaks in mice whole-body irradiated with 1Gy but not with 4Gy. NAC treatment in the absence of irradiation was not genotoxic. These data suggest that, given the safety and efficacy of NAC in humans, NAC may be useful in radiation therapy to prevent radiation-mediated genotoxicity, but does not interfere with efficient cancer cell killing. © 2009 Published by Elsevier B.V.

History and development of radiation-protective agents

Abstract: Purpose: The search for ideal protective agents for use in a variety of radiation scenarios has continued for more than six decades. This review evaluates agents and procedures that have the potential to protect against acute and late effects of ionising radiation when administered either before or after radiation exposure.Conclusion: Over the years, extensive experimental studies of radiation-protective agents have enhanced our knowledge of radiation physics, chemistry, and biology. However, translation of agents from animal testing to use in various scenarios, such as prophylactic adjuncts in radiotherapy or post-exposure treatments for potential victims of radiation accidents/incidents, has been slow. Nevertheless, a number of compounds are now available for use in a variety of radiation situations. These include agents approved by the U.S. Food and Drug Administration for use in reducing exposure to internal radionuclides (Prussian blue, calcium diethylenetriamene pentaacetate (DTPA) and zinc DTPA, po...

A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials.

Abstract: Panax ginseng C.A. Meyer is a well-known medicinal herb native to China and Korea, and has been used as a herbal remedy in eastern Asia for thousands of years. However, there is different evidence of ginseng efficacy between traditional Chinese medicine (TCM), modern pharmacological experiments and clinical trials. In TCM, ginseng is a highly valued herb and has been applied to a variety of pathological conditions and illnesses such as hypodynamia, anorexia, shortness of breath, palpitation, insomnia, impotence, hemorrhage and diabetes. Modern pharmacological experiments have proved that ginseng possesses multiple constituents (ginsenosides, polysaccharides, peptides, polyacetylenic alcohols, etc.) and actions (central nervous system effects, neuroprotective effect, immunomodulation, anticancer, etc.), ginsenosides as the active ingredients, especially, having antioxidant, antiinflammatory, antiapoptotic and immunostimulant properties. Recently, ginseng has been studied in a number of randomized controlled trials investigating its effect mainly on physical and psychomotor performance, cognitive function, immunomodulation, diabetes mellitus, cardiovascular risk factors, quality of life, as well as adverse effects. Equivocal results have been demonstrated for many of these indications. Because of the poor quality of most clinical trials on ginseng, reliable clinical data in humans are still lacking. Therefore, a broader understanding of medical knowledge and reasoning on ginseng is necessary.