Telmisartan Ameliorates Neurotrophic Support and Oxidative Stress in the Retina of Streptozotocin-Induced Diabetic Rats

Neurodegeneration is an early event in the diabetic retina which may lead to diabetic retinopathy. One of the potential pathways in damaging retinal neurons is the activation of renin angiotensin system including angiotensin II type 1 receptor (AT1R) in the diabetic retina. The purpose of this study was to determine the effect of telmisartan, an AT1R blocker on retinal level of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and tyrosine hydroxylase (TH), glutathione (GSH) and caspase activity in the diabetic rats. The dysregulated levels of these factors are known to cause neurodegeneration in diabetic retina. Three weeks streptozotocin induced diabetic rats were orally treated or untreated with telmisartan (10 mg/kg/day). After 4 weeks of treatments, the levels of BDNF and GSH were found to be increased systemically in the sera as well as in the retina of diabetic rats compared to untreated rats as measured by enzyme-linked immunosorbent assay and biochemical techniques (p < 0.05). The caspase-3 activity in the telmisartan treated diabetic retina was decreased compared to untreated diabetic rats (p < 0.05). Western blotting experiments showed the expression levels of BDNF, CNTF and TH were increased compared to untreated diabetic rats (p < 0.05). Thus, our findings show a beneficial effect of AT1R blocker telmisartan in efficiently increasing neurotrophic support, endogenous antioxidant GSH content, and decreasing signs of apoptosis in diabetic retina.     

Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by d-galactose in rat liver

d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU?+?GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.     

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion–Detorsion Model

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion–detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia–reperfusion; 4. Zinc + ischemia–reperfusion; 5. Melatonin + ischemia–reperfusion; 6. Zinc + melatonin + ischemia–reperfusion. Zinc and melatonin were administered before ischemia–reperfusion at doses of 5 and 3 mg/kg respectively, by intraperitoneal route for a period of 3 weeks. Testicular torsion–detorsion procedures consisted of ischemia for 1 h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc + melatonin groups (p < 0.001). Torsion–detorsion group has significantly lower erythrocyte GSH levels and higher plasma MDA values (p < 0.001). Serum inhibin-B and spermatogenic activity levels in the torsion–detorsion group were also significantly lower than those in the other groups (p < 0.001). However, zinc-, melatonin-, and melatonin + zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p < 0.001). The results of the study show that zinc, melatonin, and melatonin + zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia–reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.     

Association of −394C>G and −420C>G polymorphisms in the RETN gene with T2DM and CHD and a new potential SNP might be exist in exon 3 of RETN gene in Chinese

We investigated the regulation of antioxidant system under acetaminophen (AAP) toxicity. Twelve male New Zealand rabbits were divided into two groups with the following treatments: Group 1 animals were intraperitoneally injected with single saline (control). Group 2 animals were treated with intraperitoneal injection of AAP at a dose of 250 mg/kg body weight. Four hours following the treatments, blood samples were collected and the rabbits were sacrificed to collect liver samples. Hepatocellular damage was evaluated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as histopathological examinations and immunohistochemical analysis. Tissue-reduced glutathione (GSH), nitric oxide (NO^·), and malondialdehyde (MDA) levels were also measured. mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured by semi-quantitative RT-PCR. It was found that liver GSH was reduced significantly in AAP-treated rabbits (P < 0.05), while MDA and NO^· levels were increased when they were compared to control (P < 0.05). Blood AST and ALT levels were also increased following AAP treatment (P < 0.05). Hepatocellular degeneration and severe necrosis were detected in histopathological examinations. Increased immunostaining was observed for inducible nitric oxide synthase (iNOS) and nitrotyrosine in the liver. There were no changes in mRNA expression levels of SOD, CAT, and GSH-Px after AAP treatment compared to control group. These results suggest that the expression of these enzymes, which are involved in the antioxidant system, may not be altered after AAP toxicity, although classical toxic changes such as depletion of GSH, hepatocellular necrosis, and increased immunostaining for iNOS and nitrotyrosine were detected.     

Reduced Levels of Brain Derived Neurotrophic Factor (BDNF) in the Serum of Diabetic Retinopathy Patients and in the Retina of Diabetic Rats

Diabetic retinopathy (DR) is widely recognized as a neurovascular disease. Retina, being a neuronal tissue of the eye, produces neurotrophic factors for its maintenance. However, diabetes dysregulates their levels and thereby may damage the retina. Among neurotrophins, brain derived neurotrophic factor (BDNF) is the most abundant in the retina. In this study, we investigated the level of BDNF in the serum of patients with DR and also in the serum and retina of streptozotocin-induced diabetic rats. The level of BDNF was significantly decreased in the serum of proliferative diabetic retinopathy patients as compared to that of non-diabetic healthy controls (25.5 ± 8.5–10.0 ± 8.1 ng/ml, p < 0.001) as well as compared to that of diabetic patients with no retinopathy (21.8 ± 4.7–10.0 ± 8.1 ng/ml, p < 0.001), as measured by ELISA techniques. The levels of BDNF in the serum and retina of diabetic rats were also significantly reduced compared to that of non-diabetic controls (p < 0.05). In addition, the expression level of tropomyosin-related kinase B (TrkB) was significantly decreased in diabetic rat retina compared to that of non-diabetic controls as determined by Western blotting technique. Caspase-3 activity was increased in diabetic rat retina after 3 weeks of diabetes and remained elevated until 10 weeks, which negatively correlated with the level of BDNF (r = ?0.544, p = 0.013). Our results indicate that reduced levels of BDNF in diabetes may cause apoptosis and neurodegeneration early in diabetic retina, which may lead to neuro-vascular damage later in DR.     

Responses of antioxidant defenses and membrane damage to drought stress in fruit bodies of Auricularia auricula-judae

Fruit bodies of Auricularia auricula-judae are often subjected to drought stress and became dormant. The responses of antioxidant defenses and membrane damage to drought stress were investigated in this study. Picked fruit bodies were exposed to sunlight and dehydrated naturally and samples were collected at different levels of water loss (0, 10, 30, 50, and 70 %) for determination of electrolyte leakage (EL); contents of malondialdehyde (MDA), ascorbic acid (AsA) and reduced glutathione (GSH); and activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). Results showed that membrane permeability (assessed by EL) and membrane lipid peroxidation (MDA content) remained unchanged at all levels of water loss studied. Contents of AsA and GSH showed no change at 0, 10 and 30 % of water loss, however, both of them increased significantly at 50 and 70 % of water loss. SOD activity significantly increased with the rising of water loss from 0 to 30 %, reached the peak at 30 and 50 % of water loss, and then significantly decreased at 70 % of water loss. A gradual increase in POD and CAT activities was observed when water loss rose from 0 to 50 %. As water loss went up to 70 %, POD activity remained the same as that at 50 %, but CAT activity decreased. The results indicate that the increased activities of enzymatic antioxidants (SOD, CAT and POD) and contents of non-enzymatic antioxidants (AsA and GSH) in fruit bodies of A. auricula-judae can effectively scavenge reactive oxygen species, cause no damage to cell membranes as demonstrated by the unchanged EL and MDA content, and contribute to dormancy under drought stress.     

Quercetin and Vitamin C Mitigate Cobalt Chloride-Induced Hypertension through Reduction in Oxidative Stress and Nuclear Factor Kappa Beta (NF-Kb) Expression in Experimental Rat Model

The objective of the present work was to evaluate the toxic effects of cobalt chloride, a potent oxidative stress-inducing chemical, at 650 ppm in rats and the protective effect of quercetin and/or vitamin C against the cobalt chloride-induced toxicity. Thirty rats were randomly selected, and assigned to one of five groups: control, cobalt chloride, cobalt chloride + quercetin, cobalt chloride + vitamin C and cobalt chloride + quercetin + vitamin C. The exposure of rats to cobalt chloride led to a significant increase (p < 0.05) in malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) generated, but decreased nitric oxide (NO) bioavailability. Also, significant (p < 0.05) reductions were observed in the activity of glutathione peroxidase (GPx) and reduced glutathione (GSH) content in the cardiac and renal tissues. Treatment with quercetin and vitamin C reversed the effect of cobalt chloride on MDA, H₂O₂ and NO, more potently than with either of the two antioxidants, and increased the antioxidant defence system. Further, treatment of rats with quercetin and vitamin C in combination resulted in significant (p < 0.05) decreases in the systolic, diastolic, and mean arterial blood pressure of rats, relative to those exposed to cobalt chloride alone. Immunohistochemical studies revealed a greater expression of nuclear factor kappa beta (NF-kB) in the cobalt chloride group compared with the control- and antioxidants-treated rats. The results of this study suggest a protective role for quercetin and vitamin C in the amelioration of the toxic mechanisms leading to cobalt chloride-induced hypertension and its associated cardiac and renal complications in rats.     

Long-term fructose feeding changes the expression of leptin receptors and autophagy genes in the adipose tissue and liver of male rats: a possible link to elevated triglycerides

Long-term fructose consumption has been shown to evoke leptin resistance, to elevate triglyceride levels and to induce insulin resistance and hepatic steatosis. Autophagy has been suggested to function in processes such as lipid storage in adipose tissue and inflammation in liver. Autophagy and the leptin system have also been suggested to regulate each other. This study aimed to identify the changes caused by fetal undernourishment and postnatal fructose diet in the gene expression of leptin, its receptors (LEPR-a, LEPR-b, LEPR-c, LEPR-e and LEPR-f) and autophagy genes in the white adipose tissue (WAT) and liver of adult male rats in order to clarify the mechanism behind the metabolic alterations. The data clearly revealed that the long-term postnatal fructose diet decreased leptin levels (p < 0.001), LEPR (p < 0.001), especially LEPR-b (p = 0.011) and LEPR-f (p = 0.005), as well as SOCS3 (p < 0.001), ACC (p = 0.006), ATG7 (p < 0.001), MAP1LC3β (p < 0.001) and LAMP2 (p = 0.004) mRNA expression in WAT. Furthermore, LEPR (p < 0.001), especially LEPR-b (p = 0.001) and LEPR-f (p < 0.001), ACC (p = 0.010), ATG7 (p = 0.024), MAP1LC3β (p = 0.003) and LAMP2 (p < 0.001) mRNA expression in the liver was increased in fructose-fed rats. In addition, the LEPR expression in liver and MAP1LC3β expression in WAT together explained 55.7 % of the variation in the plasma triglyceride levels of the rats (R _adj. ²  = 0.557, p < 0.001). These results, together with increased p62 levels in WAT (p < 0.001), could indicate decreased adipose tissue lipid storing capacity as well as alterations in liver metabolism which may represent a plausible mechanism through which fructose consumption could disturb lipid metabolism and result in elevated triglyceride levels.     

The Effects of Levosimendan Exposure on Oxidant/Antioxidant Status and Trace Element Levels in the Pulmonary Artery of Rats

We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.     

The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats

Little is known about the effective role of Hypericum perforatum on hepatic ischemia–reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE₅₀) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE₅₀ significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment–control group (p < 0.05). In oxidative stress generated by hepatic ischemia–reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.     

Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney

The present study was designed to evaluate whether microRNA-146a and its adapter proteins (TRAF6 and IRAK1) are involved in the pathogenesis of diabetes-induced kidney damage. Male Sprague–Dawley rats were divided into control and diabetic groups (n = 6 in each). Diabetes was induced by injection of streptozotocin (55 mg/kg; i.p.) in 12 h fasted rats. Diabetic kidney damage was diagnosed by renal hypertrophy, thickened glomerular basement membrane, widened filtration slits, mesangial expansion, as well as by elevated levels of blood urea and creatinine in diabetic rats 2 months after induction of diabetes. While the expression of NF-κB mRNA and miR-146a were increased in diabetic kidney compared to the sham controls (p < 0.01 for both comparisons), the mRNA levels of IRAK1 and TRAF6 did not statistically reduce. The NF-κB activity and the concentrations of TNF-α, IL-6 and IL-1β in the kidney of diabetic rats were higher than the kidney of controls (p < 0.05 for TNF-α and NF-κB; p < 0.01 for IL-6 and IL-1β). Our results indicate that the upregulation of miR-146a was not accompanied by downregulation of inflammatory mediators in diabetic kidney. It is possible that a defect in the miR-146a-mediated negative loop provides a situation for sustained activation of NF-κB and its targets to promote cells toward abnormalities.     

The evaluation of protective and mitigating effects of vitamin C against side effects induced by radioiodine therapy

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq ¹³¹Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p?<?0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p?<?0.05). A significant decrease in the control group (p?<?0.05) and increase in group 4 (p?<?0.05) were observed in GSH level after RAIT (p?<?0.05). Mean variation of GSH was significant between control group with groups 3 (p?<?0.01) and 4 (p?<?0.01). The results indicate that activity of SOD remained unchanged in all groups (p?>?0.05). A significant increase was observed in CAT activity after RAIT in all groups (p?<?0.05), which was higher in control group than intervention groups. In groups 3 (p?<?0.05) and 4 (p?<?0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.     

Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats

We sought to determine the hepatic fibrosis-reversal effects upon simultaneous administration of lithospermate B (LAB), an anti-oxidant, and nivocasan, a caspase inhibitor, to rats compared with each compound alone. Liver fibrosis was induced in Sprague–Dawley rats by thioacetamide (TAA). Rats were treated with TAA and then given LAB and (or) nivocasan. Fibrotic areas were evaluated quantitatively by computerized morphometry. Apoptosis was assessed using a TUNEL assay, and immunohistochemical staining for malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4HNE) was performed to assess oxidative stress levels. Real-time quantitative PCR was used to quantify expression of fibrosis-related genes. The degree of hepatic fibrosis was significantly reduced in rats treated with LAB and nivocasan compared to either treatment alone (P < 0.001). Treatment with each compound significantly decreased expression of fibrosis-related genes, such as type I collagen α1 (col1α1), α-SMA and TGF-β1 (P < 0.05). Co-treatment with LAB and nivocasan further reduced col1α1 expression compared to treatment with either compound. A TUNEL assay revealed that hepatocyte apoptosis was significantly decreased in the group treated with nivocasan compared to other groups (P < 0.01). Immunohistochemistry showed a decrease in MDA and 4HNE, reflecting amelioration of oxidative stress, when LAB or LAB+nivocasan was administered compared to nivocasan alone (P < 0.01). Nivocasan was found to inhibit caspase-1, -3, -7, -9 and gliotoxin-induced death of rat-derived hepatic stellate cells was inhibited by nivocasan administration without overexpression of α-SMA. Conclusions: Co-incidental administration of LAB and nivocasan suppressed oxidative stress and apoptosis, resulting in enhanced reversal of hepatic fibrosis in rat.     

Effects of ischemic preconditioning on myocardium Caspase-3, SOCS-1, SOCS-3, TNF-α and IL-6 mRNA expression levels in myocardium IR rats

The aim of this study was to characterise the effects of ischemic preconditioning (IP) on heart function parameters (ΔST and ΔT), activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression levels and Apoptosis index in myocardium IR rats. Results showed that ΔST and ΔST values in IP group were markedly lower than those in IR group. Compared with IR group, IP significantly (p < 0.01) decreased serum CK (0.83 ± 0.09 vs 1.36 ± 0.15), LDH (5613 ± 462 vs 7106 ± 492) activities and MDA (11.32 ± 1.05 vs 15.49 ± 1.26) level, increased the serum NO (86.39 ± 7.03 vs 53.77 ± 4.27) level in IR group. The IP induced a significant decreased in myocardium Caspase-3 mRNA (0.303 ± 0.021 vs 0.515 ± 0.022) gene expression (p < 0.01) compared to IR model group. The IP induced a significant decreased in myocardium SOCS-1 (0.241 ± 0.031 vs 0.596 ± 0.036), SOCS-3 (0.258 ± 0.031 vs 0.713 ± 0.057), TNF-α (0.137 ± 0.011 vs 0.427 ± 0.035) and IL-6 (0.314 ± 0.021 vs 0.719 ± 0.064) mRNA gene expression (p < 0.01) compared to IR model group. We conclude that IP is effective in the therapy of heart disease. These findings may have implications for the clinical development of preconditioning-based therapies for ischemic heart disease.     

The Differences in the Cellular and Plasma Antioxidative Capacity Between Transient and Defined Focal Brain Ischemia: Does it Suggest Supporting Time-Dependent Neuroprotection Therapy?

There are many opened questions about the precocious role of oxidative stress in the physiopathology of the early stage of transitory ischemic attack (TIA) and defined focal brain ischemia, as well as about its correlation with clinical severity, short-lasting and clinical outcome prediction in these conditions. The study evaluates the values of glutathione (GSH), glutathione peroxidase, and superoxide dismutase (SOD) in hemolysates and total thiol content (–SH), advanced oxidation protein products (AOPP), SOD, and malondialdehyde (MDA) in plasma, in TIA and stroke patients in the early stage of their neurological onset. The results are interpreted in view of the potential relationship between tested parameters and clinical severity and clinical outcome prediction. Better hemolysates’ and total antioxidant profile with higher values of AOPP were observed in TIA compared to stroke patients (p < 0.05). The stroke patients with initially better clinical presentation showed better antioxidant profile with lower values of AOPP (p < 0.05). In TIA patients, this was observed for GSH, –SH content, and AOPP (p < 0.05), which correlated with a short risk for stroke occurrence in this group (p < 0.01). Beyond MDA values, all tested parameters showed correlation with clinical outcome in stroke patients (p < 0.05). The measurement of oxidative stress in TIA and stroke patients would be important for identifying patients’ subgroups which might receive supporting therapy providing better neurological recovery and clinical outcome. That approach might give us an additional view of a short-lasting risk of stroke occurrence after TIA, and its clinical outcome and prognosis.     

Effect of Danshen aqueous extract on serum hs-CRP, IL-8, IL-10, TNF-α levels, and IL-10 mRNA, TNF-α mRNA expression levels, cerebral TGF-β1 positive expression level and its neuroprotective mechanisms in CIR rats

To observe the effects of Danshen aqueous extract (DSAE) on the cerebral tissue and nerve stem cells in cerebral ischemia reperfusion (CIR) rats. The model rats were prepared by occlusion of the middle cerebral artery for 2 h and then by reperfusion. They were randomly divided into five groups: a control group, an CIR group and three DSAE-treated groups. As compared with the sham control group, there was significant increase (P < 0.05, P < 0.01) in the serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-8 (IL-8) levels, interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) levels, and IL-10 mRNA, TNF-α mRNA expression levels, function score, Infarct size, TUNEL + cell counts, cerebral transforming growth factor beta 1 (TGF-β1) positive expression and cerebral neuron specific enolase (NSE) levels, and decrease in fas-associated protein with death domain (FADD) and death-associated protein (Daxx) positive expression levels in the CIR group. Compared with CIR group, DSAE treatment dose-dependently significantly decreased serum hs-CRP, IL-8, IL-10, TNF-α levels, and IL-10 mRNA, TNF-α mRNA expression levels, function score, Infarct size, TUNEL + cell counts, cerebral TGF-β1 positive expression and cerebral NSE levels, and increase FADD and Daxx positive expression levels in the CIR + DSAE groups. Taken together, these results suggest that DSAE has a neuroprotective role in the CIR rats, which may be related to improvement of immunity function, proteins and genes expression.     

The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidase system

Herein, we investigate whether the NADPH oxidase might be playing a key role in the degree of oxidative stress in the senescence-accelerated mouse prone-8 (SAM-P8). To this end, the activity and expression of the NADPH oxidase, the ratio of glutathione and glutathione disulfides (GSH/GSSG), and the levels of malonyl dialdehyde (MDA) and nitrotyrosine (NT) were determined in renal tissue from SAM-P8 mice at the age of 1 and 6 months. The senescence-accelerated-resistant mouse (SAM-R1) was used as control. At the age of 1 month, NADPH oxidase activity and Nox2 protein expression were higher in SAM-P8 than in SAM-R1 mice. However, we found no differences in the GSH/GSSG ratio, MDA, NT, and Nox4 levels between both groups of animals. At the age of 6 months, SAM-R1 mice in comparison to SAM-P8 mice showed an increase in NADPH oxidase activity, which is associated with higher levels of NT and increased Nox4 and Nox2 expression levels. Furthermore, we found oxidative stress hallmarks including depletion in GSH/GSSG ratio and increase in MDA levels in the kidney of SAM-P8 mice. Finally, NADPH oxidase activity positively correlated with Nox2 expression in all the animals (r?=?0.382, P?<?0.05). Taken together, our data allow us to suggest that an increase in NADPH oxidase activity might be an early hallmark to predict future oxidative stress in renal tissue during the aging process that takes place in SAM-P8 mice.