间歇低氧对大鼠肝脏氧化应激损伤的研究

目的通过建立大鼠模型并测定间歇低氧及持续低氧大鼠肝脏中过氧化产物丙二醛（MDA）水平,探讨睡眠呼吸暂停模式间歇低氧对大鼠肝脏氧化应激损伤的机制。方法雄性Wistar大鼠96只,随机分为3组：间歇低氧组（IH）,持续低氧组（CH）和常氧对照组（SC）。分别于暴露第2、4、6、8周随机抽取8只大鼠麻醉处死,留取肝脏组织,应用化学比色方法检测大鼠肝脏MDA水平。结果大鼠肝脏MDA含量IH组明显高于CH组和sc组（均P〈0．01）,IH及CH组MDA水平随暴露时间延长逐渐增加。结论睡眠呼吸暂停模式间歇低氧能引起大鼠肝脏发生氧化应激反应而导致肝损伤,其损伤程度比持续低氧更为严重,且随时间延长而增加。     

间歇低氧-肺气肿大鼠的炎症及免疫反应特点研究

摘要:目的 建立间歇低氧(IH)-肺气肿大鼠模型, 探讨其引起炎症和免疫反应的特点。方法 60 只 Wistar 大鼠随机分成对照组、 肺气肿组、 IH 组和重叠组(肺气肿合并 IH 组)。每组 15 只。造模成功后使用流式细胞仪测定各组外周血中性粒细胞 （PMN）、 CD3+ CD8+ T 细胞、 CD3+ CD4+ T 细胞凋亡率水平。酶联免疫吸附试验 （ELISA） 法测定血浆中肿瘤坏死因子(TNF)-α、 白细胞介素 （IL） -6 水平。取大鼠肺泡灌洗液(BALF), 在光镜下计算巨噬细胞、 外周血 PMN 和淋巴细胞比例。采集肺、 肝脏、 胰腺组织和右颈动脉并进行病理评分。结果 重叠组中 PMN、 CD3+ CD8+ T 细胞凋亡率与其他 3 组相比较低, CD3+ CD4+ T 细胞凋亡率、 TNF-α、 IL-6 表达水平最高 （均 P < 0.05）。BALF 中, 肺气肿组巨噬细胞和 PMN 百分比高于其余 3 组 （均 P < 0.05）。重叠组中肺、 肝脏、 胰腺、 右颈动脉内中膜厚度的病理评分高于其他 3组 （均 P < 0.05）。结论 肺气肿合并IH 可产生更严重的系统性多器官炎症和免疫反应。     

间歇低氧小鼠血清氧化应激指标的变化及N-乙酰半胱氨酸的治疗作用

目的观察间歇低氧(I H)小鼠血清氧化应激指标的变化情况,并探讨N-乙酰半胱氨酸(NAC)的治疗作用。方法随机将50只小鼠分为对照组(A组,20只),IH组(B组,30只),分别造模3d、1周、2周、3周、4周;另设IH4周+NAC组(C组,6只)。检测各组小鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)表达水平。结果与A组同期比较,B组MDA表达均升高(P<0.05);造模1周后,SOD、GSH-PX表达均降低(P<0.05)。随低氧时间的延长,B组MDA逐渐升高,SOD、GSH-PX逐渐降低(P<0.05)。与B组比较,C组MDA降低,SOD、GSH-PX升高(P<0.05)。结论 IH可导致机体氧化应激水平增加,而NAC治疗能够改善IH导致的氧化应激反应。     

慢性间歇低氧诱发大鼠高血压模型的建立

目的:观察间歇低氧对大鼠尾动脉收缩压的影响及胸主动脉、肾小动脉病理变化。方法:16只SD雄性大鼠随机分为间歇低氧组(IH)和空白对照组(UC),每组8只,IH大鼠置于间歇低氧舱中,7 h·d~(-1),给予循环充入氮气和空气,每次循环为8 min,间歇缺氧舱内氧浓度波动于8．5%～21%,UC大鼠不予任何特殊处理。分别于实验前及实验d7,14,21．28测量大鼠尾动脉收缩压。d28处死大鼠,取标本观察胸主动脉与肾小动脉病理改变。结果:IH大鼠尾动脉收缩压逐渐升高,从第2周开始显著升高,第2,3,4周时其收缩压分别升高了13．75mmHg (P＜0．01)．22．25mmHg(P＜0．01)和29．87 mmHg(P＜0．01)。实验后两组大鼠之间比较,第1周收缩压无显著差异,第2周后IH大鼠较UC大鼠收缩压明显升高(P＜0．05或P＜0．01)。d28两组大鼠胸主动脉未见明显病理改变,但IH大鼠肾小动脉血管壁在d 28时较UC大鼠明显增厚,并有部分出现肾小动脉硬化。结论:慢性间歇低氧可导致大鼠持续性血压升高,提示阻塞性睡眠呼吸暂停低通气综合征(OSAHS)引起的长期夜间反复低氧是OSAHS患者高血压发生的重要原因,此模型的建立为OSAHS致高血压机制的深入研究提供了可行手段。     

间歇低氧的大鼠模型体内的氧化应激、炎症反应导致代谢紊乱发生的机制

目的探讨慢性间歇低氧大鼠体内的氧化应激、炎症反应导致代谢紊乱发生的机制。方法建立慢性间歇低氧的大鼠模型,模拟阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apneahypopnea syndrome,OSAHS）睡眠中发生的慢性低氧、再氧合病理生理过程。将50只雄性SD大鼠,分为慢性间歇低氧组（40只）和空白对照组（10只）。将慢性间歇低氧组的大鼠放入自制的间歇低氧动物舱内,提供间歇低氧（最低吸入氧浓度6%～7%,最高吸入氧浓度20%～21%,各维持时间5～7 s）;将空白对照组大鼠置于相同规格的间歇低氧动物舱内,给予空气脉冲供气。间歇低氧刺激总时间：8 h/d（9AM～5PM）,持续12周。实验结束后,酶联免疫吸附测定法（ELISA法）测定大鼠血清丙二醛（MDA）、超氧化物歧化酶（SOD）和hs-CRP水平;并检测代谢紊乱相关指标如空腹血糖、甘油三酯（TG）、胆固醇（CHOL）、大鼠尾动脉血压,每一个指标作为一个危险因素,没有危险因素的为正常组,仅有1个危险因素的为低危组,有2个危险因素的为高危组,有3个危险因素的为代谢综合征组（MS组）。结果根据危险因素,将慢性间歇低氧组的大鼠分为正常组,低危组,高危组,代谢综合征组。随着间歇缺氧的时间延长,发生代谢紊乱的危险因素逐渐增加,超氧化物歧化酶（SOD）活性降低,丙二醛（MDA）、hs-CRP的水平逐渐增高,与空白对照组比较差异有统计学意义（P〈0.05）。结论间歇缺氧模型大鼠体内氧化应激存在,导致慢性低度炎症反应,可能是导致阻塞性睡眠呼吸暂停低通气综合征患者发生代谢紊乱的重要机制。     

白藜芦醇对间歇低氧大鼠胰岛素抵抗的影响

目的观察白藜芦醇对间歇低氧大鼠胰岛素抵抗的影响,探讨其可能的作用机制。方法 8周龄SD雄性大鼠40只,随机分为5组,对照组(A组)、间歇低氧组(B组)、白藜芦醇低剂量组[C组,6 mg/(kg·d)]、白藜芦醇中剂量组[D组,30 mg/(kg·d)]、白藜芦醇高剂量组[E组,60 mg/(kg·d)]。C组、D组、E组大鼠间歇低氧4周,同时按不同剂量白藜芦醇灌胃。实验结束后,测大鼠空腹胰岛素和血糖水平,取肝脏,采用RT-PCR和Western blot法测定肝脏SIRT1。结果白藜芦醇干预后间歇低氧大鼠的胰岛素抵抗降低,呈剂量依赖性,伴随SIRT1的表达增高,各组间差异有统计学意义(P<0.01)。结论白藜芦醇能减轻间歇低氧大鼠的胰岛素抵抗,呈剂量依赖性,其可能是通过提高SIRT1的表达起作用。     

饮水铅暴露对大鼠脑组织 APE1 表达的影响及与氧化应激的关系研究

目的 探讨饮水铅暴露对大鼠大脑皮质、 小脑、 海马组织中脱嘌呤脱嘧啶核酸内切酶 1（APE1）表达的影响及其与氧化应激的关系。方法 40 只刚断乳雄性 SD 大鼠按体质量随机区组法均分为 5 组, 对照组自由饮用去离子水, 4 个铅暴露组分别饮用 100、 200、 400 和 800 mg/L 醋酸铅溶液, 连续染毒 60 d 后, 取大脑皮质、 小脑和海马组织, 测定各组的超氧化物歧化酶 （SOD） 活力、 过氧化氢 （H2O2） 水平和丙二醛 （MDA） 含量, 蛋白印迹法检测 APE1 蛋白在各组织中的表达。结果 铅暴露后, 大脑皮质、 小脑、 海马中 APE1 蛋白表达水平均低于对照组, 且随染铅剂量的升高呈逐渐下降趋势（P＜0.05）; 随着染铅剂量的升高, 大脑皮质、 小脑和海马中的 SOD 活力基本呈下降趋势; 而 H2O2及 MDA 含量随染铅剂量的升高基本呈逐渐升高趋势, 大脑皮质、 小脑和海马组织的 APE1 蛋白表达水平与其 SOD 活力呈正相关（r 分别为 0.619、 0.380、 0.375, P < 0.05） ,而与 H2O2水平和 MDA 含量呈负相关（r 分别为-0.472、 -0.535、 -0.436, -0.514、 -0.486、 -0.316, P < 0.05）。结论 饮水铅暴露可导致大鼠脑组织 APE1 蛋白表达水平改变,且此种改变与铅所致的氧化应激有关。     

间歇低氧下大鼠肝脏NF-κB和ICAM-1的变化及抗氧化剂Tempol的干预作用

目的:探讨间歇低氧对大鼠肝脏炎性介质核因子-κB(NF-κB)、细胞间黏附分子-1(ICAM-1)的影响和4-羟基-2,2,6,6-四甲基哌啶(Tempol)的干预作用及可能机制。方法:应用慢性间歇低氧(CIH)大鼠模型,模拟阻塞性睡眠呼吸暂停综合征(OSAS)慢性间歇低氧/再氧合的病理生理过程。将32只雄性Wistar大鼠随机分为常规间歇低氧组(CIH组),间歇低氧Tempol干预组(CIH+T组),间歇低氧生理盐水对照组(CIH+NS组)和常氧对照组(NC组),共4组,每组8只,CIH各组最低氧浓度均为5%,低氧频率均为每小时30次,每天暴露8 h。暴露6周后,用酶联免疫吸附法(Elisa)测定大鼠肝脏中NF-κB,ICAM-1的水平。结果:通过向计算机控制的不同频率的低氧舱中循环充入氮气和正常氧浓度空气,可以造成不同频率间歇低氧,从而可以模拟OSAS患者不同频率的睡眠低氧状况。与CIH组、CIH+NS组比较,CIH+T组NF-κB,ICAM-1水平均下降(P<0.05);CIH+T组与NC组NF-κB比较,差异有统计学意义(P<0.05),但ICAM-1水平差异无统计学意义(P=0.119)。结论:慢性间歇低氧可以导致大鼠肝脏炎性损伤。Tempol能够通过清除氧自由基(ROS)进而抑制NF-κB的激活,从而减轻CIH对大鼠肝脏的炎症损伤。     

间充质干细胞移植减轻大鼠肺气肿及氧化应激的探讨

目的研究间充质干细胞(MSCs)移植在肺气肿大鼠氧化应激和肺气肿发展过程中的作用。方法 26只雌性SD大鼠随机分为对照组(A组,n=8),肺气肿组(B组,n=8),肺气肿+MSCs移植组(C组,n=10),将B与C组大鼠在香烟烟雾中暴露14周,制作肺气肿大鼠模型,C组大鼠予MSCs移植。完成4次MSCs移植后的2、4周分别处死C组大鼠各1只,观察MSCs在肺气肿大鼠肺部的定植情况;MSCs移植8周后同时处死各组大鼠,观察大鼠肺组织病理形态,并进行定量分析;用硫代戊巴比妥法测定血清和肺组织匀浆中丙二醛(MDA)的水平,用WST-1法测定各组血清和肺组织匀浆中超氧化物歧化酶(SOD)的水平。结果 MSCs移植后2周及4周,C组大鼠肺组织内均可见标记过的MSCs,随着时间的推移,肺组织内MSCs比例逐渐减少。B组和C组大鼠的肺组织呈现肺气肿样改变,B组和C组大鼠肺组织的平均内衬间隔(MLI)高于A组,平均肺泡数(MAN)明显低于A组,B组大鼠肺组织的MLI高于C组,MAN低于C组(P<0.05)。B组和C组大鼠血清及肺组织中MDA高于A组,SOD低于A组,B组血清及肺组织中MDA高于C组,SOD低于C组(P<0.05)。结论 MSCs移植可能通过降低氧化应激水平对大鼠肺气肿发挥治疗作用。     

Assessment of oxidative stress induced by gold nanorods following intra-tracheal instillation in rats

Gold nanorods (GNRs) are used for their wide variety of applications in various industries. There is a little availability of data related to toxicity and ecological implications of these GNRs. The study evaluated the oxidative stress induction following intra-tracheal instillation of 1 and 5?mg/kg b.w. doses of 10 and 25?nm GNRs by estimating various oxidative stress markers including lipid peroxidation (malondialdehyde; MDA), glutathione (GSH), superoxide dismutase (SOD), catalase and total antioxidant capacity (TAC) after 1?day, 1?week, 1?month, and 3?months post exposure periods. The results have shown increased MDA levels and decreased GSH levels following 1?day and 1?week post exposure periods, indicating induction of oxidative stress. Also, the SOD, catalase and TAC levels were significantly decreased following exposure of both 10 and 25?nm GNRs after 1?day and 1?week after exposures, indicating the inhibition of antioxidant defense mechanisms. Moreover, the 10?nm GNRs at 5?mg/kg dose displayed greater changes in all the estimated parameters, representing dose and size based induction of oxidative stress by GNRs. In contrast, a little change was observed during 1?month and 3?months post exposure periods, may be due to recovery. Finally, the GNRs induced dose-size-dependent oxidative stress induction by various oxidative stress markers following intra-tracheal instillation in rats.     

Chronic treatment with tempol does not significantly ameliorate renal tissue hypoxia or disease progression in a rodent model of polycystic kidney disease

1. In the present study, we tested whether polycystic kidney disease (PKD) is associated with renal tissue hypoxia and oxidative stress, which, in turn, contribute to the progression of cystic disease and hypertension.
2. Lewis polycystic kidney (LPK) rats and Lewis control (Lewis) rats were treated with tempol (1 mmol/L in drinking water) from 3 to 13 weeks of age or remained untreated.
3. The LPK rats developed polyuria, uraemia and proteinuria. At 13 weeks of age, LPK rats had greater mean arterial pressure (1.5‐fold), kidney weight (sixfold) and plasma creatinine (3.5‐fold) than Lewis rats. Kidneys from LPK rats were cystic and fibrotic.
4. Renal hypoxia was evidenced by staining for pimonidazole adducts and hypoxia‐inducible factor (HIF)‐1α in cells lining renal cysts and upregulation of HIF‐1α and its downstream targets vascular endothelial growth factor (VEGF), glucose transporter‐1 (Glut‐1) and heme oxygenase 1 (HO‐1). However, total HO activity did not differ greatly between kidney tissue from LPK compared with Lewis rats.
5. Renal oxidative and/or nitrosative stress was evidenced by ninefold greater immunofluorescence for 3‐nitrotyrosine in kidney tissue from LPK compared with Lewis rats and a > 10‐fold upregulation of mRNA for p47phox and gp91phox. Total renal superoxide dismutase (SOD) activity was sevenfold less and expression of SOD1 mRNA was 70% less in kidney tissue from LPK compared with Lewis rats. In LPK rats, tempol treatment reduced immunofluorescence for 3‐nitrotyrosine and HIF1A mRNA while upregulating VEGF and p47phox mRNA expression, but otherwise had little impact on disease progression, renal tissue hypoxia or hypertension.
6. Our findings do not support the hypothesis that oxidative stress drives hypoxia and disease progression in PKD.

     

间歇低氧对大鼠肺组织RhoA/ROCK通路及肺血管新生肌化的影响

目的探讨间歇低氧(IH)对大鼠肺组织Rho A/ROCK通路及肺血管新生肌化的影响。方法将40只Wistar雄性大鼠随机分为对照组和IH组各20只,对照组:间歇正常氧暴露(21%O2);IH组:IH暴露(5%~21%O2),持续4周。暴露结束后,2组均采用Real-time PCR和Western blot检测肺组织Rho A、ROCK m RNA和蛋白表达情况,免疫组化法测定肺组织和肺动脉的增殖细胞核抗原(PCNA)及α-平滑肌肌动蛋白(SM-α-actin)的表达情况。结果IH组肺组织Rho A m RNA(0.463±0.067 vs 0.182±0.040)、ROCK m RNA(0.384±0.062 vs 0.192±0.052)、Rho A蛋白(0.827±0.065 vs 0.424±0.075)及ROCK蛋白(0.488±0.088 vs 0.336±0.102)表达水平均高于对照组(均P<0.05);IH组肺组织PCNA[(54.67±1.80)%vs(9.14±0.91)%]、肺动脉PCNA[(49.40±1.21)%vs(8.38±1.13)%]、肺组织SM-α-actin[(42.66±1.63)%vs(35.44±1.41)%]与肺动脉SM-α-actin[(62.62±2.53)%vs(45.54±2.58)%]表达水平均明显高于对照组(均P<0.05)。结论 Rho A/ROCK传导通路在IH所致肺动脉高压发病机制中可能起着重要作用;IH可通过促进肺动脉的新生肌化进一步促进肺动脉压力升高。     

Morphological transformation and oxidative stress induced by cyanide in Syrian hamster embryo (SHE) cells.

Cyanide is a well-established poison known for its rapid lethal action and toxicity. Although long-term mammalian studies examining the carcinogenic potential of cyanide have not been previously reported, cyanide was reported to be positive in Salmonella typhimurium mutagenesis assay and induced aneuploidy in DROSOPHILA: To further evaluate the carcinogenic potential of cyanide, the ability of cyanide to induce morphological transformation in Syrian hamster embryo (SHE) cells was studied. Cyanide induced a dose-dependent increase in morphological transformation in SHE cells following a 7-day continuous treatment. A significant increase in transformation was observed at potassium cyanide doses of 200 microM and greater. Transformation induced by cyanide was inhibited in a dose-related manner by vitamin E, suggesting a role of oxidative stress in the induction of morphological transformation by cyanide. Further, it was shown that 500 microM cyanide induced oxidative DNA damage in SHE cells, evidenced by the formation of 8-hydroxy-2'-deoxyguanosine (50-66% increase over control). The induction of oxidative stress by cyanide involved an early and temporal inhibition of antioxidant enzymes (catalase and superoxide dismutase) as well as an increased production of reactive oxygen species (1.5- to 2.0-fold over control).     

Mechanisms for the induction of oxidative stress in Syrian hamster embryo cells by acrylonitrile.

Chronic administration of acrylonitrile to rats resulted in an increase in the incidence of glial neoplasms of the brain. Recent studies have shown that acrylonitrile induces oxidative stress in rat brain and cultured rat glial cells. Acrylonitrile also induces morphological transformation concomitant with an increase in the formation of oxidized DNA in Syrian Hamster Embryo (SHE) cells in a dose-dependent manner. The mechanism for the induction of oxidative stress in SHE cells remains unresolved. The present study examined the effects of acrylonitrile on enzymatic and nonenzymatic antioxidants in SHE cells. SHE cells were treated with subcytolethal doses of acrylonitrile (0, 25, 50, and 75 microg/ml) for 4, 24, and 48 h. Acrylonitrile (50 microg/ml and 75 microg/ml) increased the amount of reactive oxygen species in SHE cells at all time points. Glutathione (GSH) was depleted and catalase and superoxide dismutase activities were significantly decreased in SHE cells after 4 h of treatment. The inhibition of these antioxidants was temporal, returning to control values or higher after 24 and 48 h. Xanthine oxidase activity was increased following 24 and 48 h treatment with acrylonitrile. 1-aminobenzotriazole, a suicidal P450 enzyme inhibitor, attenuated the effects of acrylonitrile on catalase and xanthine oxidase in SHE cells, suggesting that P450 metabolism is required for acrylonitrile to produce its effects on these enzymes. Additional studies showed that in the absence of metabolic sources acrylonitrile had no effect on either catalase or superoxide dismutase activity. These results suggest that the induction of oxidative stress by acrylonitrile involves a temporal decrease in antioxidants and increase in xanthine oxidase activity that is mediated by oxidative metabolism of acrylonitrile.     

Effects of perindopril and hydrochlorothiazide on selected indices of oxidative stress in the blood of elderly patients with essential hypertension

1. The aim of the present study was to determine the effect of hypotensive therapy with a diuretic (hydrochlorothiazide) and an angiotensin-converting enzyme inhibitor (perindopril) on selected oxidative stress parameters in the blood of elderly patients with essential hypertension. 2. Studies were performed in 45 elderly patients with essential hypertension at baseline and after the 45th day of perindopril (n = 25) or hydrochlorothiazide (n = 20) therapy, as well as in 25 young and 25 elderly normotensive subjects. The following parameters were measured: systolic and diastolic blood pressure, nitric oxide (NO), carbonyl groups and malondialdehyde (MDA) concentrations, as well as the activity of ceruloplasmin (Cp) oxidase, Cu-Zn superoxide dismutase (SOD-1) and catalase (CAT). 3. The activity of SOD-1 and NO levels were reduced with age. 4. Compared with elderly controls, hypertensive subjects showed increases in baseline MDA, carbonyl group concentrations and Cp oxidase activity and decreases in NO levels and SOD-1 and CAT activities. 5. Treatment with perindopril, but not hydrochlorothiazide, resulted in significant increases in SOD-1 and CAT activities and decreases in MDA concentration and Cp oxidase activity. Both therapies decreased the level of carbonyl groups and increased NO levels. 6. Angiotensin-converting enzyme inhibitor therapy has significant anti-oxidant effects that may be important in the treatment of elderly patients with essential hypertension.     

仙人掌多糖组分对大鼠脑片氧化应激损伤的保护作用

目的研究仙人掌多糖对H_2O_2所致大鼠大脑皮质和海马脑片氧化应激损伤是否有保护作用。方法大鼠离体皮质和海马脑片与2mmol·L-1H_2O_2共孵育30min造成脑片的氧化应激损伤,分别于加入H_2O_2前加入仙人掌多糖作用30min,与H2O2同时加入仙人掌多糖作用30min或在H2O2损伤之后加入仙人掌多糖作用2h。TTC染色法检测脑片活性,并检测脑片培养液中乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活性,谷胱甘肽(GSH)含量和总抗氧化能力(T-AOC)。结果H2O2孵育30min明显损伤大鼠海马和皮质脑片,TTC染色A490nm值下降,LDH释放增加,GSH含量和总抗氧化能力降低。加入H_2O_2前预先加入仙人掌多糖0.333和1.67mg·L-1作用30min显著抑制上述H2O2所致脑片损伤,使受损脑片孵育液中GSH含量增加,SOD活性和总抗氧化能力升高。结论仙人掌多糖能够减轻H2O2所致大鼠大脑皮质和海马脑片的氧化应激损伤,其机制可能与其增强机体的抗氧化能力有关。     

Evaluation of oxidative stress induction in rats following exposure to silver nanorods

The study investigated the oxidative stress induction by the 10 and 25?nm silver nanorods (SNRs) following intra-tracheal instillation in rats after 1?day, 1 week, 1 month and 3 months post instillation periods at 1 and 5?mg/kg b.w. doses. The blood was withdrawn by retro orbital plexus method after exposure periods and different oxidative stress markers were estimated. The results showed that the both sizes of SNRs induced increased levels of malondialdehyde (MDA) and depleted glutathione (GSH) levels after 1?day and 1 week post exposure periods. The 10 and 25?nm SNRs at both doses displayed that significantly reduced levels of superoxide dismutase (SOD) and catalase following 1?day and 1 week post exposure periods. Also, the results have shown that decrease in total antioxidant capacity (TAC) of both sizes of SNRs significantly following 1?day and 1 week post exposure periods, indicating the oxidative stress induction by SNRs. In spite, there were no significant changes in oxidative stress markers following 1 month and 3 months post exposure periods may be due to recovery. The increased levels of MDA and decreased levels of GSH, SOD, catalase and TAC activity are strongly associated to ROS production and lipid peroxidation, suggesting the induction of oxidative stress in rats. The 10?nm SNRs at 5?mg/kg b.w. dose exposures in rats have shown greater changes in all oxidative stress parameters, indicating the greater induction of oxidative stress when compared with the 25?nm SNRs, representing the size–dose-dependent induction of oxidative stress of SNRs.