The senescence accelerated mouse prone 8 (SAMP8): A novel murine model for cardiac aging

Because cardiovascular disease remains the major cause of mortality and morbidity world-wide, there remains a compelling need for new insights and novel therapeutic avenues. In this regard, the senescence-accelerated mouse prone 8 (SAMP8) line is a particularly good model for studying the effects of aging on cardiovascular health. Accumulating evidence suggests that this model may shed light on age-associated cardiac and vascular dysfunction and disease. These animals manifest evidence of inflammation, oxidative stress and adverse cardiac remodeling that may recapitulate processes involved in human disease. Early alterations in oxidative damage promote endoplasmic reticulum stress to trigger apoptosis and cytokine production in this genetically susceptible mouse strain. Conversely, pharmacological treatments that reduce inflammation and oxidative stress improve cardiac function in these animals. Therefore, the SAMP8 mouse model provides an exciting opportunity to expand our knowledge of aging in cardiovascular disease and the potential identification of novel targets of treatment. Herein, we review the previous studies performed in SAMP8 mice that provide insight into age-related cardiovascular alterations.     

Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100 μg; ≥1.4 mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6 μg; ≥0.3 mg/kg) elicited acute toxicity in terms of reduced weight gain, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12.5 and 25 μg on a range of parameters. However, mice that survived a high dose (50 μg; 2.7 mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results indicate that alveolar deposition of ZnO NP may cause significant adverse health effects.     

Effects of garlic powder supplementation on insulin resistance,oxidative stress,and body composition in patients with non-alcoholic fatty liver disease: A randomized controlled clinical trial

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Insulin resistance, oxidative stress, and obesity are major contributors to NAFLD pathogenesis. The effects of garlic powder supplementation on these risk factors in patients with NAFLD was investigated.MethodsIn this 12-wk, randomized controlled clinical trial, ninety patients with NAFLD were randomly assigned to two groups. The treatment group received four tablets of garlic (each coated tablet contained 400 mg garlic powder) daily and the control group received four tablets of placebo (each coated tablet contained 400 mg starch).ResultsA significant decrease was seen in the treatment group compared to the control group in waist circumference (P = 0.001), body fat percent (P < 0.001), serum concentration of fasting blood sugar (P = 0.01), insulin (P < 0.001), homeostatic model assessment for insulin resistance (P < 0.001), and malondialdehyde (P < 0.001), as well as significant increase in skeletal muscle mass (P = 0.002), serum concentration of superoxide dismutase (P < 0.001), and total antioxidant capacity (P < 0.001).ConclusionGarlic powder supplementation improved risk factors of NAFLD. Further studies are needed to determine the effects of garlic on hepatic features in patients with NAFLD. The study protocol was registered at Iranian clinical trials website under code IRCT20170206032417N4.     

水陆地黄汤联合盐酸贝那普利对气阴两虚夹瘀型糖尿病肾病氧化应激及临床指标的影响

目的:观察水陆地黄汤对气阴两虚夹瘀型糖尿病肾病氧化应激及临床指标的影响。方法:60例气阴两虚夹瘀型糖尿病肾病患者随机分为对照组与联合组,每组30例,对照组给予盐酸贝那普利片10 mg,1次/d,联合组在对照组基础上加服水陆地黄汤,1剂/d。治疗12周后观察两组氧化应激指标:谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)及临床指标:空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)、尿微量白蛋白(mALB)、24 h尿蛋白定量(24 hU-PQ)、肾小球滤过率(eGFR)的变化及临床症状的改善。结果:联合组治疗总有效率为90.0%,与对照组56.7%比较,差异有统计学意义(P<0.05);治疗后联合组MDA较治疗前均降低(P<0.05),SOD、GSH-Px均高于治疗前(P<0.05),与对照组比较,差异有统计学意义(P<0.05);联合组FPG、2 hPG、HbA1c、mALB、24 hU-PQ、eGFR较治疗前均降低(P<0.01)。结论:水陆地黄汤联合盐酸贝那普利可改善气阴两虚夹瘀型糖尿病肾病氧化应激状态,明显缓解临床症状,延缓病程进展。     

Baicalein attenuates the neuroinflammation in LPS-activated BV-2 microglial cells through suppression of pro-inflammatory cytokines,COX2/NF-κB expressions and regulation of metabolic abnormality

Baicalein (5,6,7-trihydroxyflavone), isolated from the root of traditional Chinese herb Scutellaria baicalensis Georgi, has anti-inflammatory and anti-oxidative activities. This study explored the protective and modulatory mechanisms of baicalein on neuroinflammation, oxidative stress and metabolic abnormality in lipopolysaccharide (LPS)-activated BV-2 cells. Our results demonstrated that treatment with baicalein remarkably restrained the production of pro-inflammatory factors including nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in LPS-activated BV-2 cells. Moreover, baicalein significantly inhibited reactive oxygen species (ROS) production, decreased cyclooxygenase-2 (COX-2) and nuclear factor-b (NF-κB)/p65 expression. ¹H NMR metabolomics analysis revealed that 12 differential metabolites were regulated by baicalein, implicated in alanine, aspartate and glutamate metabolism, glutathione metabolism, arginine and proline metabolism, D-glutamine and D-glutamate metabolism. In conclusion, these results indicated that baicalein has protective and modulatory effects on neuroinflammation and oxidative stress in LPS-activated BV-2 cells.     

Melatonin Treatment Ameliorates Hyperhomocysteinemia-Induced Impairment of Erectile Function in a Rat Model

BackgroundHyperhomocysteinemia (HHcy) has been reported to be strongly correlated with the occurrence of erectile dysfunction (ED), but the mechanisms are not fully understood. Moreover, whether melatonin could be a potential treatment of HHcy-induced ED needs to be elucidated.AimThe aim of this study was to investigate the effects of melatonin on HHcy-induced ED and the potential mechanisms via modulating oxidative stress and apoptosis.MethodsThe Sprague-Dawley (SD) rat model of HHcy was induced by 7% methionine (Met)-rich diets. 36 male SD rats were randomly distributed into 3 groups (n = 12 per group): control group, 7% Met group, and 7% Met + melatonin (Mel; 10 mg/kg, intraperitoneal injection) treatment group. After 4 weeks, the erectile function of all rats was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum were also analyzed by immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, Western blotting, and polymerase chain reaction.OutcomesHHcy-induced ED rat models were successfully established, and Mel could preserve erectile function mainly through inhibiting oxidative stress via the Erk1/2/Nrf2/HO-1 signaling pathway and suppression of apoptosis.ResultsErectile function was significantly reduced in the rats with HHcy compared with that in the control group and was ameliorated in the HHcy rats treated with Mel. Compared with the control group, the rats in the HHcy group showed the following: (1) higher levels of total plasma homocysteine; (2) fewer neuronal nitric oxide synthase-positive cells in the corpus cavernous; (3) higher levels of reactive oxygen species and malondialdehyde, higher expression levels of nicotinamide adenine dinucleotide phosphate oxidase, and lower activities of superoxide dismutase, indicating an overactivated oxidative stress; (4) lower expression levels of Erk1/2/Nrf2/HO-1 signaling pathway components; and (5) higher levels of apoptosis, as determined by the expression levels of Bax, Bcl-2, and caspase 3. Mel treatment improved the erectile response, as well as histologic and molecular alterations.Clinical TranslationOur study on a rodent model of HHcy provided evidence that Mel could be a potential therapeutic method for HHcy-related ED.ConclusionsMel treatment improves erectile function in rats with HHcy probably by potential antioxidative stress activity. This finding provides evidence for a potential new therapy for HHcy-induced ED.Tang Z, Song J, Yu, Z, et al. Melatonin Treatment Ameliorates Hyperhomocysteinemia-Induced Impairment of Erectile Function in a Rat Model. J Sex Med 2019;16:1506–1517.     

The effects of ginger supplementation on markers of inflammatory and oxidative stress: A systematic review and meta‐analysis of clinical trials

The present systematic review and meta‐analysis was conducted to investigate the effects of ginger supplementation on markers of inflammatory and oxidative stress. PubMed, Embase, Scopus, and Web of Science were systematically searched to identify relevant clinical trials evaluating the effects of ginger on serum CRP (C‐reactive protein), TNF‐α (tumor necrosis factor‐alpha), IL‐6 (interleukin‐6), PGE2 (prostaglandin E2), TAC (total antioxidant capacity), and MDA (malondialdehyde) from inception up to September 2019. Mean difference and 95% confidence intervals were pooled using a random‐effects model. Potential publication bias was assessed using visual inspection of funnel plot and Egger's weighted regression tests. After excluding irrelevant records, 20 full‐text articles that included 25 separate studies were included to the meta‐analysis. Pooled results of this study indicated a statistically significant effect of ginger on serum CRP, TNF‐α, IL‐6, TAC, and MDA levels following ginger supplementation in compared to the controls. Also, the effects of ginger on serum PGE2 was marginally significant. Moreover, the high heterogeneity was disappeared in subgroup analysis performed by age, duration, dosage, and quality. This current analysis indicates that ginger supplementation has a significant effects on serum inflammatory and oxidative stress markers.     

Ecotoxicological effects on Scenedesmus obliquus and Danio rerio Co-exposed to polystyrene nano-plastic particles and natural acidic organic polymer

The importance of attention to unravel the interaction of nano-plastic particles (NPs) with natural acidic organic polymer (NAOP) in freshwater environment should not be neglected. However, toxicological data available for the interaction between NPs and NAOP remain limited. Here, we investigate the toxicological effects of three model polystyrene (PS) NPs with different functional groups (unmodified, amino- and carboxyl-modified PS NPs) on two freshwater organisms of different trophic levels (Scenedesmus obliquus and Danio rerio) in the absence and presence of two classes of NAOP, namely fulvic acid and humic acid. The NAOP interaction with the NPs is shown to alter oxidative stress and disturb membrane function in S. obliquus cells to a certain extent. Combined oxidative stress responses to the NPs and NAOP in D. rerio as a function of their mixture levels showed inhibition, alleviation, and reinforce. Changes in cellular oxidative stress and membrane function depended on the concentration and types of both NPs and NAOP. Furthermore, the characterization parameters of the NPs were important for the explanation of the ecotoxicological mechanism of the NPs in the presence of NAOP. Our findings emphasized the critical role of NAOP in the fate and toxicity of plastic particles in freshwater environment.