scholarly journals Curcumin Ameliorates Benzo[a]pyrene-Induced DNA Damages in Stomach Tissues of Sprague-Dawley Rats

2019 ◽  
Vol 20 (22) ◽  
pp. 5533 ◽  
Author(s):  
Kyeong Seok Kim ◽  
Na Yoon Kim ◽  
Ji Yeon Son ◽  
Jae Hyeon Park ◽  
Su Hyun Lee ◽  
...  

Benzo[a]pyrene (BaP) is a well-known carcinogen formed during the cooking process. Although BaP exposure has been implicated as one of the risk factors for lung cancer in animals and humans, there are only limited data on BaP-induced gastrointestinal cancer. Therefore, this study investigated the protective effects of curcumin on BaP-induced DNA damage in rat stomach tissues. BaP (20 mg/kg/day) and curcumin (50, 100, or 200 mg/kg) were administered daily to Sprague-Dawley rats by oral gavage over 30 days. Curcumin was pre-administered before BaP exposure. All rats were euthanized, and liver, kidney, and stomach tissues were removed at 24 h after the last treatment. We observed that aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose levels were significantly reduced in rats treated with high dose co-administration of curcumin (200 mg/kg) compared to BaP alone. The expression levels of cytochrome P450 (CYP) 1A1 and CYP1B1 were significantly increased in the liver of rats treated with BaP. However, co-administration of curcumin (200 mg/kg) with BaP markedly reduced CYP1A1 expression in a dose-dependent manner. Furthermore, plasma levels of BaP-diolepoxide (BPDE) and BaP metabolites were significantly reduced by co-administration of curcumin (200 mg/kg). Additionally, co-administration of curcumin (200 mg/kg) with BaP significantly reduced the formation of BPDE-I-DNA and 8-hydroxydeoxy guanosine (8-OHdG) adducts in the liver, kidney, and stomach tissues. The inhibition of these adduct formations were more prominent in the stomach tissues than in the liver. Overall, our observations suggest that curcumin might inhibit BaP-induced gastrointestinal tumorigenesis and shows promise as a chemopreventive agent.

Author(s):  
A. Torres Duarte ◽  
Z. Zukowska-Grojec ◽  
A.K. Myers

Neuropeptide Y (NPY) is a multi-functional peptide localized in a number of tissues besides the brain, and its expression is high in strains of mice with autoimmune disease. Functionally, along with its neurotransmitter role, NPY has multiple effects on both vascular tissues and tissues involved in immune responses. Previous studies demonstrated that immunoreactive NPY (i-NPY) exists in large quantities in platelets and bone marrow of some species, and suggested its release during platelet aggregation by collagen. Because NPY has been hypothesized to have a role in a number of pathophysiological states in which platelets are involved, including immune responses, hypertension and vascular smooth muscle proliferation, we sought to further characterize platelet i-NPY content and release by a diverse group of physiological platelet agonists. Platelet rich plasma and gel filtered platelets were prepared from citrated whole blood of male Sprague Dawley rats. Platelet content and concentration of i-NPY were quantified by RIA. Platelet aggregation responses (turbidometric method) and release of i-NPY were measured in rat platelet preparations stimulated by a thromboxane agonist (U44069), collagen, thrombin and ADP. All agents induced dose-dependent aggregation, although ADP and U44069 were weak agonists in citrated platelet rich plasma, ADP only inducing primary aggregation. Total i-NPY content in platelet rich plasma of Sprague-Dawley rats was 32.1±3.8 pmol/ml; more than 20 pmol/ml was released into supernatant of aggregating platelets stimulated with high dose thrombin or collagen during secondary, irreversible aggregation. Although U44069 and ADP both stimulated i-NPY release in a dose-dependent manner, release was substantially lower than with the other agonists. We conclude that i-NPY release from rat platelets is associated mainly with secondary, irreversible aggregation, and can be produced by a variety of platelet stimulating agents as part of the platelet release reaction. The present study and other recent studies demonstrate wide variability in platelet i-NPY content between and within species. Investigation of the genetic regulation of i-NPY content in platelets could offer new insights into the relationship between NPY and pathophysiology of the immune and cardiovascular systems.


2012 ◽  
Vol 46 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Mariana Abreu ◽  
Delia Aguado ◽  
Javier Benito ◽  
Ignacio A Gómez de Segura

This study aimed to estimate the reduction in the minimum alveolar concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane ( n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.


2002 ◽  
Vol 282 (2) ◽  
pp. G317-G323 ◽  
Author(s):  
Jeffrey B. Schwimmer ◽  
Looi Ee ◽  
Shuqin Zheng ◽  
Patrick Tso

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.


2020 ◽  
Vol 39 (11) ◽  
pp. 1565-1581
Author(s):  
S Iqbal ◽  
F Jabeen ◽  
C Peng ◽  
MU Ijaz ◽  
AS Chaudhry

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.


1977 ◽  
Author(s):  
I.B. Holmes

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.


2016 ◽  
Vol 7 (3) ◽  
pp. 409-420 ◽  
Author(s):  
T.M. Marques ◽  
E. Patterson ◽  
R. Wall ◽  
O. O’Sullivan ◽  
G.F. Fitzgerald ◽  
...  

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaofang Yu ◽  
Xinjin Chi ◽  
Shan Wu ◽  
Yi Jin ◽  
Hui Yao ◽  
...  

This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecificα2receptor blocker) + high dose Dex (group B1), ARC239 (a specificα2B/creceptor blocker) + high dose Dex (group B2), and BRL-44408 (a specificα2Areceptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (allP<0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 throughα2Areceptor, increases the antioxidant levels, and attenuates renal injury during OALT.


1983 ◽  
Vol 69 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Franco Zunino ◽  
Odoardo Tofanetti ◽  
Adriana Besati ◽  
Ennio Cavalletti ◽  
Giuseppina Savi

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.


2014 ◽  
Vol 34 (1) ◽  
pp. 65-73 ◽  
Author(s):  
C Zhou ◽  
Y Zhang ◽  
S Yin ◽  
Z Jia ◽  
A Shan

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Qi Shen ◽  
Weijing Ye ◽  
Xiaoli Hu ◽  
Chuchu Zhao ◽  
Lulu Zhou ◽  
...  

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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