ABSTRACT
<p><b>Objective</b>To explore the antagonistic effect of vitamin E (VE) on male reproductive toxicity induced by di-2-ethylhexyl phthalate (DEHP) in pubertal SD rats and its underlying mechanisms.</p><p><b>METHODS</b>Thirty 5-week-old male SD rats were randomly divided into five groups of equal number, corn oil control, low-dose (10 mg/kg/d), medium-dose (100 mg/kg/d) and high-dose DEHP exposure (500 mg/kg/d), and VE intervention (high-dose DEHP + VE ［100 mg/kg/d］), and treated respectively for 30 successive days. At 3 days after treatment, the testes of the animals were harvested for determination of the oxidative stress index, serum reproductive hormone levels, cauda epididymal sperm parameters, and expressions of cell apoptosis-related genes and proteins.</p><p><b>RESULTS</b>Compared with the control group, the rats of the medium- and high-dose DEHP groups showed significant decreases in the levels of such serum reproductive hormones as follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T), sperm parameters as average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), straightness (STR), linearity (LIN) and wobble (WOB), and the activities of superoxide dismutase (SOD) and glutathione peroxide (GSH-Px), but significant increases were observed in the latter two groups in the content of malondialdehyde (MDA)(［3.32±0.87］ nmol/mg pro vs ［2.13±0.49］ nmol/ mg pro), mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio, and protein expressions of Cytochrome C and Caspase-3. In comparison with the high-dose DEHP group, the VE intervention group exhibited remarkably increased serum LH and T levels, sperm VAP, VSL, VCL, STR and WOB, and activities of SOD and GSH-Px, but markedly decreased mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio as well as the protein expressions of Cytochrome C and Caspase-3 in the testis tissue (P<0.05).</p><p><b>CONCLUSIONS</b>Exposure to DEHP induces androgen secretion disorders, causes oxidative damage to the testicular tissue, activates the mitochondrial apoptosis pathway in the testis, and ultimately reduces the quality of epididymal sperm, while VE can protect the rat testis from DEHP-induced reproductive toxicity.</p>
Subject(s)
Animals , Male , Rats , Antioxidants , Pharmacology , Apoptosis , Genetics , Autophagy-Related Protein 5 , Metabolism , Caspase 3 , Metabolism , Diethylhexyl Phthalate , Epididymis , Follicle Stimulating Hormone , Blood , Luteinizing Hormone , Blood , Malondialdehyde , Metabolism , Mitochondria , Oxidative Stress , Oxidoreductases , Metabolism , Random Allocation , Rats, Sprague-Dawley , Reproduction , Spermatozoa , Physiology , Superoxide Dismutase , Metabolism , Testis , Testosterone , Blood , Vitamin E , PharmacologyABSTRACT
This study is to investigate protective effect of safflor yellow B (SYB) against vascular endothelial cells (VECs) injury induced by angiotensin-II (Ang-II). VECs were cultured and divided into six groups: control group, Ang-II group, Ang-II + SYB (1 micromolL(-1)) group, Ang-II + SYB (10 micromolL(-1)) group, Ang-II + SYB (100 micromolL(-1)) group and Ang- II + verapamil (10 micromolL(-1)) group. Except control group, all of VECs in other groups were treated with Ang- II at the final concentration of 0.1 micromolL(-1). Mitochondria membrane potential (MMP) and free calcium concentration ([Ca2+]i) were measured by laser scanning confocal microscopy, and mitochondria complex IV activity was detected by BCA method. The levels of reactive oxygen species (ROS) in VECs were analyzed by fluorescence detector and apoptosis of VECs was observed by flow cytometer. Caspase 3 was determined by Western blotting method. Comparing with control group, Ang-II was able to increase [Ca2+]i and ROS level, decrease MMP level, inhibit complex IV activity and enhance caspase 3 activity in VECs, as a result, enhance apoptosis of VECs. But SYB could significantly reduce the result induced by Ang- II relying on different dosages (P < 0.05 or P < 0.01). SYB was able to eliminate the effect of Ang-II on VECs via regulating [Ca2+]i, mitochondrial structure and function and inhibiting apoptosis.
Subject(s)
Humans , Angiotensin II , Antioxidants , Pharmacology , Apoptosis , Calcium , Metabolism , Carthamus tinctorius , Chemistry , Caspase 3 , Metabolism , Cells, Cultured , Chalcone , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Electron Transport Complex IV , Metabolism , Endothelial Cells , Cell Biology , Metabolism , Membrane Potential, Mitochondrial , Mitochondrial Proton-Translocating ATPases , Metabolism , Plants, Medicinal , Chemistry , Reactive Oxygen Species , Metabolism , Vasoconstrictor AgentsABSTRACT
<p><b>OBJECTIVE</b>To study the protective effect of ligusticum chuanxiong phthalides on cerebral ischemia in rats and its related mechanism of action.</p><p><b>METHOD</b>Middle cerebral artery occlusion (MCAO) model, thrombosis formation, platelet aggregation and hemorrheological parameters were measured to evaluate the protective effect of ligusticum chuanxiong phthalides.</p><p><b>RESULT</b>Ligusticum chuanxiong phthalides could markedly decrease the infarct size and behavior deficits score, inhibit the thrombus formation and platelet aggregation, ameliorate hemorrheological parameters with a dose-dependent manner in rats.</p><p><b>CONCLUSION</b>Ligusticum chuanxiong phthalides has protective effects on focal cerebral ischemia in rats, and its mechanism may be relevant to its inhibition of platelet-dependent thrombosis and amelioration of hemorrheological parameters.</p>
Subject(s)
Animals , Male , Rats , Benzofurans , Pharmacology , Blood Viscosity , Brain Ischemia , Blood , Pathology , Dose-Response Relationship, Drug , Hematocrit , Infarction, Middle Cerebral Artery , Blood , Pathology , Ligusticum , Chemistry , Neuroprotective Agents , Pharmacology , Plants, Medicinal , Chemistry , Platelet Aggregation , Rats, Wistar , Venous ThrombosisABSTRACT
<p><b>AIM</b>To study the effects of hydroxysafflor yellow A (HSYA) on the mitochondrial function of cortex mitochondrial during cerebral ischemia in rats.</p><p><b>METHODS</b>Rat focal cerebral ischemia model in rats was established by ligation of middle cerebral central artery. Cortex mitochondria were isolated and prepared for the measurement of membrane fluidity, swelling, respiratory function, activities of mitochondrial respiratory enzymes and superoxide dismutase (SOD), contents of phospholipid, malondial dehyde (MDA) and Ca2+ to evaluate the function of mitochondria.</p><p><b>RESULTS</b>Focal cerebral ischemia resulted in severe neuronal mitochondrial injuries, which could be alleviated by i.v. HSYA (10, 20 mg x kg(-1)), and nimodipine (Nim, 1.0 mg x kg(-1)). The swelling of mitochondria was ameliorated, the decomposability of membrane phospholipid was decreased, the membrane fluidity of mitochondria was increased, HSYA also significantly inhibited the decrease in the activities of respiratory enzymes and SOD of mitochondria, and the increase in MDA and Ca2+ levels caused by cerebral ischemia in rats.</p><p><b>CONCLUSION</b>HSYA showed a protective action against the cortex mitochondrial injuries in rats induced by cerebral ischemia. The mechanisms may be derived from reducing lipid peroxides, inhibiting Ca2+ overload, scavenging free radicals and improving the energy metabolism.</p>