Hydrogen peroxide-induced impairment of reactivity in rat isolated aorta: potentiation by 3-amino-1,2,4-triazole

1. In this study the impairment induced by hydrogen peroxide of vascular reactivity and the role of endogenous catalase in protection against this impairment was assessed in isolated rings of rat aorta.
2. Incubation with hydrogen peroxide at 1 mM, but not at 0.1 mM, for 15, 30 or 60 min followed by washout depressed, in a time-dependent manner, the subsequent ability of endothelium-containing and endothelium-denuded rings to contract to phenylephrine.
3. Incubation with 3-amino-1,2,4-triazole (50 mM, 90 min, followed by washout) to inhibit endogenous catalase had no effect by itself on subsequent phenylephrine-induced contraction. However, pretreatment with 3-amino-1,2,4-triazole did lead to a profound enhancement of the ability of hydrogen peroxide (1 mM, present for the final 30 min of the 90 min incubation, followed by washout) to depress phenylephrine-induced contraction in both endothelium-containing and endothelium-denuded rings.
4. Incubation with hydrogen peroxide at 1 mM, but not at 0.1 mM, for 15, 30 or 60 min followed by washout inhibited, in a time-dependent manner, the subsequent ability of acetylcholine (10 nM–3 μM) to induce endothelium-dependent relaxation. Furthermore, incubation with hydrogen peroxide 1 mM (30 min, followed by washout) also inhibited relaxation induced by glyceryl trinitrate (1–100 nM) or isoprenaline (10 nM–3 μM) in endothelium-denuded rings.
5. Incubation with 3-amino-1,2,4-triazole (50 mM, 90 min, followed by washout) had no effect by itself on relaxation induced by acetylcholine, glyceryl trinitrate or isoprenaline. In contrast, pretreatment with 3-amino-1,2,4-triazole led to profound enhancement of the ability of hydrogen peroxide (1 mM, present for final 30 min of the 90 min incubation) to block relaxation to acetylcholine, glyceryl trinitrate or isoprenaline.
6. On the basis of the actions of 3-amino-1,2,4-triazole, it is likely that endogenous catalase plays an important role in the protection of vascular reactivity of rat aorta against oxidant damage by high (1 mM) but not lower (0.1 mM) concentrations of hydrogen peroxide. The data are consistent with the promotion of non-selective damage to the vascular smooth muscle cells by hydrogen peroxide, but endothelial damage may also be sustained.

     

膳食蛋白质对荷瘤小鼠生长的影响

将72只昆明种雌性小鼠随机分为高蛋白饲养组和低蛋白饲养组,分别在两组中设立对照组和实验组,实验组小鼠接种艾氏腹水瘤。3周喂养实验表明:高蛋白各组小鼠体重高于低蛋白组,且高蛋白荷瘤组小鼠瘤径大于低蛋白组瘤组。高蛋白组和低蛋白组,荷瘤小鼠肝过氧化氢酶和超氧化物歧化酶活性均低于对照组(P<0.01;P<0.05),而荷瘤小鼠肝过氧化脂质明显高于对照组(P<0.05)。结果提示:患瘤早期,可能存在一个“营养适宜期”,患瘤后期增加营养,要采取谨慎态度。     

Evaluation of whole blood catalase estimation for diagnosis of malignancy

Whole blood catalase levels were estimated using a disc flotation method in 209 random patients with a wide variety of malignancies. Fifty patients had received no treatment, and the remainder, although having undergone prior therapy, had recurrent or metastatic disease at the time of the study. No relationship was found between the presence of cancer and catalase levels. A direct relationship was found for catalase with hemoglobin levels in both normal and patients' samples. Whole blood catalase is of no value in diagnosis and monitoring of cancer. The decreased catalase values found here and reported previously by others are the result of low hemoglobin levels found in many patients with cancer.     

Gene expression of antioxidant enzymes in experimental diabetic neuropathy

Chronic hyperglycemia results in a large deficit in nerve blood flow. Both autoxidative- and ischemia-induced lipid peroxidation occurs, with resultant peripheral sensory neuropathy in streptozotocin-induced diabetes in the rat. Free radical defenses, especially involving antioxidant enzymes, have been suggested to be reduced, but scant information is available on chronic hyperglycemia. We evaluated the gene expression of glutathione peroxidase, catalase, and superoxide dismutase (cuprozinc and manganese separately) in L4,5 dorsal root ganglion (DRG) and superior cervical ganglion, as well as enzyme activity of glutathione peroxidase in DRG and sciatic nerve in experimental diabetic neuropathy of 3 months and 12 months durations. We also evaluated nerve electrophysiology of caudal, sciatic-tibial, and digital nerves. A nerve conduction deficit was seen in all nerves in experimental diabetic neuropathy at both 3 and 12 months. Gene expression of glutathione peroxidase, catalase, cuprozinc superoxide dismutase, and manganese superoxide dismutase were not reduced in experimental diabetic neuropathy at either 3 or 12 months. Catalase mRNA was significantly increased in experimental diabetic neuropathy at 12 months. Glutathione peroxidase enzyme activity was normal in sciatic nerve. We conclude that gene expression is not reduced in peripheral nerve tissues in very chronic experimental diabetic neuropathy. Changes in enzyme activity may be related to duration of diabetes or due to post-translational modifications.     

Catalase-mimetic gold nanoparticles inhibit the antagonistic action of Lactobacillus gasseri toward foodborne enteric pathogens in associative cultures

Gold nanoparticles (AuNPs) have been previously shown to induce gut dysbiosis during colitis in mice, but the underlying mechanism is not clear yet. Here, we evaluated the effects of AuNPs (5?nm diameter, coated with tannic acid, polyvinylpyrrolidone or citrate) on H₂O₂ accumulation and pathogen antagonization by an intestinal strain of Lactobacillus gasseri under aerobic cultural conditions. AuNPs (0.65?μg/mL) reduced over 50% of H₂O₂ accumulation by L. gasseri, and significantly inhibited the antagonistic action of L. gasseri on growth of four foodborne enteric pathogens, i.e. Salmonella enterica serovar Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus in associative cultures.     

Free radicals generated by xanthine oxidase-hypoxanthine damage adenylate cyclase and ATPase in gerbil cerebral cortex

The generation of superoxide radicals from xanthine oxidase-hypoxanthine in a particulate fraction of gerbil cerebral cortex influenced the activity of the synaptic enzyme adenylate cyclase, as well as Mn²⁺- and Na⁺,K⁺-sensitive forms of ATPase. Low concentrations of xanthine oxidase actually elevated the sensitivity of adenylate cyclase to GTP, GTP + norepinephrine (NE), and forskolin but not significantly to Mn²⁺. Higher levels of xanthine oxidase elicited a marked inhibition of these responses. The stimulation of adenylate cyclase mechanisms requiring GTP (GTP, forskolin, and NE) was more susceptible than was Mn²⁺, suggesting that the guanine nucleotide stimulatory protein was more vulnerable to free radical attack than the catalytic site of adenylate cyclase. superoxide dismutase (SOD), but not catalase, partially protected the forskolin-sensitive enzyme from the action of xanthine oxidase-hypoxanthine. A combination of SOD plus catalase preserved enzyme responses to forskolin. In comparison, additions of SOD plus mannitol or catalase plus flunarizine were less effective. The sensitivity of the particulate ATPase to Mn²⁺ was more labile to the consequence of superoxide formation than Na⁺, K⁺-ATPase. In this regard the Ca²⁺, Mg²⁺ sensitivity of the enzyme was reduced only to a marginal extent. The findings might be analogous toin vivo data in which cerebral adenylate cyclase and Na⁺, K⁺-ATPase are damaged following postischemic reperfusion in gerbils, a process thought to be mediated by free radicals.     

Functional heterogeneity of colony-stimulating factor-induced human monocyte-derived macrophages

Objectives:   Macrophages (Mφs) have various functions and play a critical role in host defense and the maintenance of homeostasis. Mφs exist in every tissue in the body, but Mφs from different tissues exhibit a wide range of phenotypes with regard to their morphology, cell surface antigen expression and function, and are called by different names. However, the precise mechanism of the generation of macrophage heterogeneity is not known. In the present study, the authors examined the functional heterogeneity of Mφs generated from human monocytes under the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF).
Methodology:   CD14 positive human monocytes (Mos) were incubated with M-CSF and GM-CSF for 6–7 days to stimulate the generation of M-CSF-induced monocyte-derived Mφs (M-Mφs) and GM-CSF-induced monocyte-derived Mφs (GM-Mφs), respectively. The expression of cell surface antigens and several functions such as antigen presenting cell activity, susceptibility to oxidant stress, and the susceptibility to HIV-1 and mycobacterium tuberculosis infection were examined.
Results:   GM-Mφs and M-Mφs are distinct in their morphology, cell surface antigen expression, and functions examined. The phenotype of GM-Mφs closely resembles that of human Alveolar-Mφs (A-Mφs), indicating that CSF-induced human monocyte-derived Mφs are useful to clarify the molecular mechanism of heterogeneity of human Mφs, and GM-Mφs will become a model of human A-Mφs.     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.