Nickel nanoparticles induce hepatotoxicity via oxidative and nitrative stress-mediated apoptosis and inflammation

Nickel nanoparticles (Ni NPs) are utilized extensively in various industrial applications. However, there are increasing concerns about potential exposure to Ni NPs and consequent health effects. The aim of this study was to assess Ni NPs-induced liver toxicity in Sprague Dawley rats. Twenty-five rats were exposed to Ni NPs via intraperitoneal injection at doses of 15, 30, and 45 mg/kg per body weight for 28 days. Results from ICP-MS analysis showed an increase in the concentration of Ni NPs in a dose-dependent manner. The liver dysfunction was indicated by considerable production of ALT, AST, ALP, LDH, and TB in Ni NPs-treated rats. Histological examination demonstrated liver injuries (inflammatory cells, congestion, necrosis, and pyknosis) in exposed rats with dose-dependent severity of pathologies by semi-quantitative histograding system. To explore the toxicological pathways, we examined oxidative stress biomarkers and detected Ni NPs significantly elevated the levels of MDA and LPO while decreasing the levels of CAT and GSH. All the changes in biomarkers were recorded in a dose-dependent relationship. In addition, we found upregulated NF-kβ indicating activation of inflammatory cytokines. ELISA results of serum revealed a remarkable increase of nitrative stress markers (iNOS and NO), ATPase activity, inflammatory cytokine (IL-6, IL-1β, and TNF-α), and apoptotic mediators (caspase-3 and caspase-9) in Ni NPs-treated groups than the control. In summary, the result of this study provided evidence of hepatotoxicity of Ni NPs and insightful information about the involved toxic pathways, which will help in health risk assessment and management, related preventive measures for the use of Ni-NPs materials.

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In Utero Exposure to Di(n)butyl Phthalate Reduces Testicular Testosterone and Testes Size in a Dose-Dependent Manner in Harlan Sprague Dawley Fetal Rats.

Biology of Reproduction ◽

10.1093/biolreprod/81.s1.636 ◽

2009 ◽

Vol 81 (Suppl_1) ◽

pp. 636-636

Author(s):

Kembra L. Howdeshell ◽

Johnathan Furr ◽

Christy R. Lambright ◽

Vickie Wilson ◽

L. Earl Gray

Keyword(s):

In Utero ◽

In Utero Exposure ◽

Dependent Manner ◽

Sprague Dawley ◽

Fetal Rats ◽

Testes Size ◽

Butyl Phthalate ◽

Dose Dependent

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Oxidative stress biomarkers in the gills of the bivalve Mactra stultorum exposed to acrylamide

Scientia Marina ◽

10.3989/scimar.04993.11a ◽

2020 ◽

Vol 84 (2) ◽

Author(s):

Wafa Trabelsi ◽

Chaima Fouzai ◽

Imene Chetoui ◽

Safa Bejaoui ◽

Khaoula Telahigue ◽

...

Keyword(s):

Oxidative Stress ◽

Ache Activity ◽

Reduced Glutathione ◽

Lipid Hydroperoxides ◽

Dependent Manner ◽

Advanced Oxidation Protein Products ◽

Oxidative Stress Biomarkers ◽

Stress Biomarkers ◽

The Subject ◽

Dose Dependent

Acrylamide (ACR) is among the most deleterious pollutants in the environment and presents a serious risk to humans and ecosystems. The purpose of this study was to assess its effects when administered at different concentrations (5, 10 and 20 mg L–1) to evaluate antioxidant status in the gills of Mactra stultorum. Our results showed, after five days of treatment, an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), reduced glutathione (GSH), ascorbic acid (Vit C) and metallothionein (MDA) levels in gills of treated clams compared with controls. Moreover, an increase in superoxide dismutase (SOD) and a significant decrease in glutathione peroxidase (GPx) activities were also observed. Acrylamide induced neurotoxicity, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Overall, our results indicated that oxidative stress may be considered one of the mechanisms behind acrylamide toxicity in bivalves, although the subject requires more research.

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Glutamine promotes triglyceride absorption in a dose-dependent manner

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2002.282.2.g317 ◽

2002 ◽

Vol 282 (2) ◽

pp. G317-G323 ◽

Cited By ~ 5

Author(s):

Jeffrey B. Schwimmer ◽

Looi Ee ◽

Shuqin Zheng ◽

Patrick Tso

Keyword(s):

Amino Acid ◽

Amino Acid Mixture ◽

Lipid Absorption ◽

Acid Mixture ◽

Dependent Manner ◽

Sprague Dawley ◽

Feeding Tubes ◽

Mesenteric Lymph ◽

Sprague Dawley Rats ◽

Dose Dependent

Dietary proteins may play a role in lipid absorption. Whether amino acids are specifically involved is unknown. We hypothesized that enterally administered l-glutamine (l-Gln) given with a lipid meal increases triglyceride (TG) absorption in rats. Mesenteric lymph fistulae and gastroduodenal feeding tubes were placed in adult male Sprague-Dawley rats. The animals received an enteral bolus of Intralipid (5 ml) followed by enteral infusion of increasing concentrations of l-Gln in saline (0, 85, 170, or 340 mM) or equimolar concentrations of the inactive isomer d-Gln or an essential amino acid mixture without Gln. Lymph was collected continuously for 6 h and analyzed for TG content. Animals infused with 85 mM l-Gln had a 64% increase in total TG output vs. controls ( P < 0.05) despite no difference in lymph flow rate. Total TG output for animals infused with 340 mMl-Gln declined by 43% vs. controls ( P < 0.05). The effect of Gln in promoting lymphatic fat transport is specific to l-Gln and not shared by d-Gln or an equivalent amino acid mixture. l-Gln is capable of either promoting or impairing lymphatic TG transport in a dose-dependent manner.

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Cinnamomum cassia ameliorates Ni-NPs-induced liver and kidney damage in male Sprague Dawley rats

Human & Experimental Toxicology ◽

10.1177/0960327120930125 ◽

2020 ◽

Vol 39 (11) ◽

pp. 1565-1581

Author(s):

S Iqbal ◽

F Jabeen ◽

C Peng ◽

MU Ijaz ◽

AS Chaudhry

Keyword(s):

Dependent Manner ◽

Sprague Dawley ◽

Cinnamomum Cassia ◽

Preliminary Information ◽

Sprague Dawley Rats ◽

Liver And Kidney ◽

Altered Blood ◽

Biochemical Analyses ◽

Dose Dependent ◽

Different Doses

Nickel nanoparticles (Ni-NPs) have been widely used in various industries related to electronics, ceramics, textiles, and nanomedicine. Ambient and occupational exposure to Ni-NPs may bring about potential detrimental effects on animals and humans. Thus, there is a growing effort to identify compounds that can ameliorate NPs-associated pathophysiologies. The present study examined Cinnamomum cassia ( C. cassia) bark extracts (CMBE) for its ameliorative activity against Ni-NPs-induced pathophysiological and histopathological alterations in male Sprague Dawley rats. The biochemical analyses revealed that dosing rats with Ni-NPs at 10 mg/kg/body weight (b.w.) significantly altered the normal structural and biochemical adaptations in the liver and kidney. Conversely, supplementations with CMBE at different doses (225, 200, and 175 mg/kg/b.w. of rat) ameliorated the altered blood biochemistry and reduced the biomarkers of liver and kidney function considerably ( p < 0.05) in a dose-dependent manner. However, the best results were at 225 mg/kg/b.w. of rat. The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated liver and kidney damages. Future investigations are needed to explore C. cassia mechanism of action and isolation of single constituents of C. cassia to assess their pharmaceutical importance accordingly.

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Collagen-Induced Reduction in Rat Circulating Platelet Count: Influence of Platelet Function Inhibitors

10.1055/s-0039-1682682 ◽

1977 ◽

Author(s):

I.B. Holmes

Keyword(s):

Platelet Count ◽

Platelet Function ◽

Test System ◽

Collagen Fibrils ◽

Dependent Manner ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Dose Dependent ◽

Double Lumen Cannula ◽

Antiinflammatory Compound

The effect on circulating platelet count of repeated intravenous infusions of collagen fibrils was measured in male OFA Sprague-Dawley rats (400-550 g). Citrated blood was pumped from the left carotid artery of anaesthetized animals, via a siliconized double-lumen cannula, into the manifold of a Technicon Autocounter, for continuous registration of platelet count. Native collagen fibrils (Collagenreagent ‘Horm’) were infused intravenously for 1 min at 15 min intervals. Successive increasing collagen doses (20-320 pg/kg) induced dose-dependent reduction in platelet count, measured as absolute platelet number disappearing from the circulation. Repeated infusion of collagen 160 pg/kg produced constant, partially reversible, reduction in platelet count. Several known inhibitors of platelet aggregation were investigated in the described test system. Collagen effects were inhibited in a dose-dependent manner to a maximum of 50-60 %, and drug activity was thus quantitated on the basis of dose producing 30 % inhibition (ID30): prostaglandin E1 (1.6 pg/kg/min i.v. infusion), SH-869 (1.1 mg/kg i.v.), aspirin (33.1 mg/kg p.o.), proquazone, a new non-steroidal antiinflammatory compound (5.0 mg/kg p.o.). That part of the collagen response not inhibited might be attributed to the initial phase of platelet adhesion to collagen, known to be relatively refractive to platelet function inhibitors.

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The osteoprotective effect ofHerba epimedii(HEP) extractin vivoandin vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neh101 ◽

2005 ◽

Vol 2 (3) ◽

pp. 353-361 ◽

Cited By ~ 70

Author(s):

Fang Xie ◽

Chun-Fu Wu ◽

Wan-Ping Lai ◽

Xu-juan Yang ◽

Pik-Yuan Cheung ◽

...

Keyword(s):

Serum Alkaline Phosphatase ◽

Calcium Excretion ◽

Dependent Manner ◽

Sprague Dawley ◽

Alp Activity ◽

Post Menopausal Osteoporosis ◽

Ovx Rats ◽

Rankl Mrna ◽

Umr 106 ◽

Dose Dependent

Herba epimedii(HEP) is one of the most frequently used herbs prescribed for treatment of osteoporosis in China. In the present study, thein vivoeffects of HEP extract on bone metabolism were evaluated using 4-month-old ovariectomized (OVX) or sham-operated (Sham) female Sprague-Dawley rats orally administered with HEP extract (110 mg kg−1d−1), 17ß-estrogen (2 mg kg−1d−1) or its vehicle for 3 months. HEP extract significantly decreased urinary calcium excretion, suppressed serum alkaline phosphatase (ALP) activity and urinary deoxypyridinoline levels in OVX rats (P< 0.05 versus vehicle-treated OVX rats). Histomorphometric analysis indicated that HEP extract could prevent OVX-induced bone loss by increasing tibial trabecular bone area and decreasing trabecular separation in OVX rats (P< 0.05 versus vehicle-treated OVX group). Thein vitroeffects of HEP extract were also studied using rat osteoblast-like UMR 106 cells. HEP extract significantly stimulated cell proliferation in a dose-dependent manner (P< 0.01 versus vehicle-treated) and increased ALP activity at 200 μgml−1 (P< 0.01 versus vehicle-treated) in UMR 106 cells. It modulated osteoclastogenesis by increasing osteoprotegrin (OPG) mRNA and decreasing receptor activator of NF-κB ligand (RANKL) mRNA expression, resulting in a dose-dependent increase in OPG/RANKL mRNA ratio (P< 0.01 versus vehicle-treated). Taken together, HEP treatment can effectively suppress the OVX-induced increase in bone turnover possibly by both an increase in osteoblastic activities and a decrease in osteoclastogenesis. The present study provides the evidence that HEP can be considered as a complementary and alternative medicine for treatment of post-menopausal osteoporosis.

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Protective Effect of Reduced Glutathione against CIS-Dichlorodiammine Platinum (II)–Induced Nephrotoxicity and Lethal Toxicity

Tumori Journal ◽

10.1177/030089168306900204 ◽

1983 ◽

Vol 69 (2) ◽

pp. 105-111 ◽

Cited By ~ 38

Author(s):

Franco Zunino ◽

Odoardo Tofanetti ◽

Adriana Besati ◽

Ennio Cavalletti ◽

Giuseppina Savi

Keyword(s):

Reduced Glutathione ◽

Body Weight Loss ◽

Dependent Manner ◽

Sprague Dawley ◽

Antitumor Effects ◽

Partial Protection ◽

Lethal Toxicity ◽

Sprague Dawley Rats ◽

Serum Blood Urea Nitrogen ◽

Dose Dependent

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.

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Biochemical changes and oxidative stress induced by zearalenone in the liver of pregnant rats

Human & Experimental Toxicology ◽

10.1177/0960327113504972 ◽

2014 ◽

Vol 34 (1) ◽

pp. 65-73 ◽

Cited By ~ 18

Author(s):

C Zhou ◽

Y Zhang ◽

S Yin ◽

Z Jia ◽

A Shan

Keyword(s):

Oxidative Stress ◽

Messenger Rna ◽

Experimental Period ◽

Normal Diet ◽

Dependent Manner ◽

Sprague Dawley ◽

Pregnant Rats ◽

Sprague Dawley Rats ◽

Albumin Content ◽

Dose Dependent

The aim of the present research was to examine the toxic influence of different doses of zearalenone (ZEN) on the liver, especially oxidative stress induced by ZEN on the liver. A total of 48 pregnant Sprague-Dawley rats were randomly assigned into 4 treatments groups with 12 animals in each. The rats were fed with a normal diet treated with 0 mg/kg (control), 50 mg/kg (treatment 1), 100 mg/kg (treatment 2), or 150 mg/kg (treatment 3) ZEN in feed on gestation days (GDs) 0–7 and then all the rats were fed with a normal diet on GDs 8–20. The experimental period lasted 21 days. The results showed that exposure to ZEN induced increase in aspartate amino transferase, alanine aminotransferase, and alkaline phosphatase activities and decrease in total protein and albumin content in a dose-dependent manner and also induce decrease in superoxide dismutase and glutathione peroxidase activities and increase in malondialdehyde content in a dose-dependent manner in the serum and the liver. The increased transcription of cytochrome P450 2E1 (CYP2E1) was detected in the liver after exposure to ZEN. These results suggested that ZEN not only caused damage in the liver of pregnant rats in a dose-dependent manner but also induced the messenger RNA expression of CYP2E1 in the liver.

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The Effects of Guizhi Fuling Capsule Drug Serum on Uterine Leiomyoma Cells and Its Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/2393640 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Qi Shen ◽

Weijing Ye ◽

Xiaoli Hu ◽

Chuchu Zhao ◽

Lulu Zhou ◽

...

Keyword(s):

Uterine Leiomyoma ◽

Treatment Time ◽

Annexin V ◽

Dependent Manner ◽

Inhibition Rate ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Cell Inhibition ◽

Dose Dependent ◽

Saline Lavage

Aims. To observe the effects of Guizhi Fuling Capsule (GZFLC) drug serum on uterine leiomyoma cells and explore its mechanism. Main Methods. Sixty Sprague Dawley rats were randomly divided into two groups (normal saline lavage group and GZFLC lavage group), then, respectively, blank serum and GZFLC drug serum were collected, and finally human uterine leiomyoma cells were treated. Human leiomyoma tissues were collected from 20 patients who underwent uterine leiomyomas operations, and leiomyoma cells were primary cultured. The leiomyoma cells were treated by GZFLC drug serum in different concentrations (10%, 20%, and 30%) and variable treatment time (12 h, 24 h, 36 h, 48 h, and 72 h). Cell proliferation was observed using CCK8 assay. Flow cytometry and Annexin V/PI were used to assay the effects of GZFLC drug serum on cell apoptosis. Western blot analysis was used to assay the effects of GZFLC drug serum on TSC2, FOXO, and 14-3-3γ expression in uterine leiomyoma cells. Key Findings. In the concentrations of 10%～30%, GZFLC drug serum could inhibit proliferation of leiomyoma cells in dose-dependent manner; at the time of 36 h, cell inhibition rate was at the peak; GZFLC drug serum could induce apoptosis of leiomyoma also in a dose-dependent manner, and apoptosis rate quickly achieved maximum at 12 h time points, and then second apoptosis peak appeared at 36 h. Compared to nontreatment group, TSC2, FOXO, and 14-3-3γ expressions in drug serum group were significantly changed after 12 h treatment. Significance. GZFLC drug serum can efficiently inhibit the proliferation and induce apoptosis of leiomyoma cells, which is related to the 14-3-3γ pathway.

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Phenyl N -tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats

Anesthesiology ◽

10.1097/aln.0b013e3181ca31bd ◽

2010 ◽

Vol 112 (2) ◽

pp. 432-439 ◽

Cited By ~ 73

Author(s):

Hee Kee Kim ◽

Yan Ping Zhang ◽

Young Seob Gwak ◽

Salahadin Abdi

Keyword(s):

Neuropathic Pain ◽

Free Radical ◽

Mechanical Allodynia ◽

Intraperitoneal Administration ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Dependent Manner ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Dose Dependent

Background Paclitaxel is a widely used chemotherapeutic drug for breast and ovarian cancer. Unfortunately, it induces neuropathic pain, which is a dose-limiting side effect. Free radicals have been implicated in many neurodegenerative diseases. The current study tests the hypothesis that a free radical scavenger plays an important role in reducing chemotherapy-induced neuropathic pain. Methods Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on four alternate days (days 0, 2, 4, and 6) in male Sprague-Dawley rats. Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, was administered intraperitoneally as a single dose or multiple doses before or after injury. Mechanical allodynia was measured by using von Frey filaments. Results The administration of paclitaxel induced mechanical allodynia, which began to manifest on days 7-10, peaked within 2 weeks, and plateaued for at least 2 months after the first paclitaxel injection. A single injection or multiple intraperitoneal injections of PBN ameliorated paclitaxel-induced pain behaviors in a dose-dependent manner. Further, multiple administrations of PBN starting on day 7 through day 15 after the first injection of paclitaxel completely prevented the development of mechanical allodynia. However, an intraperitoneal administration of pbn for 8 days starting with the first paclitaxel injection did not prevent the development of pain behavior. Conclusions This study clearly shows that PBN alleviated mechanical allodynia induced by paclitaxel in rats. Furthermore, our data show that PBN given on days 7 through 15 after the first paclitaxel injection prevented the development of chemotherapy-induced neuropathic pain. This clearly has a clinical implication.

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