scholarly journals Reduction of the sevoflurane minimum alveolar concentration induced by methadone, tramadol, butorphanol and morphine in rats

2012 ◽  
Vol 46 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Mariana Abreu ◽  
Delia Aguado ◽  
Javier Benito ◽  
Ignacio A Gómez de Segura
Keyword(s):  
Minimum Alveolar Concentration ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
High Doses ◽  
Dose Dependent

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.

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

2010 ◽  
Vol 112 (2) ◽  
pp. 432-439 ◽  
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.

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 ◽  
...  
Keyword(s):  
High Dose ◽  
Dependent Manner ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Dna Damages ◽  
Glucose Levels ◽  
Cooking Process ◽  
Sprague Dawley Rats ◽  
Cyp1a1 Expression ◽  
Dose Dependent

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.

Role of cytochrome P-450 in endogenous antipyresis

2000 ◽  
Vol 279 (2) ◽  
pp. R455-R460 ◽  
Author(s):  
Wieslaw Kozak ◽  
Matthew J. Kluger ◽  
Anna Kozak ◽  
Maciej Wachulec ◽  
Karol Dokladny
Keyword(s):  
Arachidonic Acid ◽  
Intraperitoneal Administration ◽  
Dependent Manner ◽  
Epoxyeicosatrienoic Acid ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Rats And Mice ◽  
Dose Dependent ◽  
Cytochrome P 450

In previous reports, we (15, 18) and others (29) demonstrated data showing that various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis. The aim of this study was to further test the hypothesis that the P-450-dependent epoxygenase pathway of arachidonic acid is part of the homeostatic system to control the height of fever. Sprague-Dawley rats were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide (LPS; 80 μg/kg). We demonstrate that intraperitoneal administration of P-450 inducers (bezafibrate and dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a dose-dependent manner. In complementary experiments, rats were implanted with brain cannulas in addition to the biotelemeters. Various isomers of epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to 10 μg/rat to test their influence on LPS-induced fever in rats. Four of five isomers were antipyretic in a dose-dependent manner. The most potent antipyretic isomers were 11,12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9-EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part of the endogenous antipyretic system.

scholarly journals Effects of intraperitoneal administration of gabapentin on the minimum alveolar concentration of isoflurane in adult male rats

2012 ◽  
Vol 46 (2) ◽  
pp. 108-113 ◽  
Author(s):  
D T Boruta ◽  
G Sotgiu ◽  
F J Golder
Keyword(s):  
Adult Male ◽  
Drug Testing ◽  
Minimum Alveolar Concentration ◽  
Linear Regression Analysis ◽  
Intraperitoneal Administration ◽  
Male Rats ◽  
High Dose ◽  
Dependent Manner ◽  
Clinically Significant ◽  
Dose Dependent

Gabapentin has been used to treat a variety of conditions in both human and veterinary medicine, including seizures, neuropathies and chronic pain. However, little information is known about the effects of gabapentin on the minimum alveolar concentration (MAC) of volatile anaesthetics. In this study, we investigated the effect of intraperitoneal administration of gabapentin on isoflurane MAC in adult male rats and hypothesized that gabapentin would decrease MAC in a dose-dependent manner. Using a standard MAC study protocol, we compared five treatment groups (G) receiving 0 (G0), 30 (G30), 100 (G100), 300 (G300) and 1000 (G1000) mg/kg gabapentin intraperitoneally and compared post-drug MAC values among groups and with corresponding baseline MAC values determined in each group prior to drug testing. The average baseline isoflurane MAC value was 1.45 ± 0.17%, which did not differ significantly between groups (1.47 ± 0.23% [G30], 1.46 ± 0.23% [G100], 1.48 ± 0.18% [G300] and 1.42 ± 0.2% [G1000]). In the G300 and G1000 groups, the isoflurane MAC value decreased significantly by 19% and 18%, respectively, from corresponding baseline values ( P< 0.05, when compared with G0). Linear regression analysis revealed a negative correlation between blood gabapentin concentration and percent change in MAC ( R2 = 0.43; P< 0.05) but not dose. In conclusion, high-dose intraperitoneal gabapentin decreased isoflurane MAC. However, the effect was small and not dose-dependent, and is unlikely to be clinically significant.

Agonist-Induced Release of Neuropeptide Y by Platelets

1996 ◽  
Vol 9 (1) ◽  
pp. 1-8
Author(s):  
A. Torres Duarte ◽  
Z. Zukowska-Grojec ◽  
A.K. Myers
Keyword(s):  
Platelet Aggregation ◽  
Immune Responses ◽  
Neuropeptide Y ◽  
Platelet Rich Plasma ◽  
High Dose ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Irreversible Aggregation ◽  
Dose Dependent

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.

scholarly journals Etoricoxib in the Prevention of Rat Mammary Carcinogenesis

2007 ◽  
Vol 76 (4) ◽  
pp. 613-618
Author(s):  
P. Orendáš ◽  
I. Ahlers ◽  
P. Kubatka ◽  
E. Ahlersová ◽  
B. Bojková ◽  
...  
Keyword(s):  
Experimental Studies ◽  
Mammary Carcinogenesis ◽  
Selective Inhibitor ◽  
Control Group ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Antiinflammatory Drugs ◽  
Sprague Dawley Rats ◽  
Cox 2 ◽  
Dose Dependent

Several experimental studies suggest that non-steroidal antiinflammatory drugs have chemopreventive effects in mammary carcinogenesis. In this study, tumour suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2) etoricoxib in the prevention of N-methyl-Nnitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley rats were evaluated. Etoricoxib was administered in the diet, at two concentrations: 1) 0.01 mg/g (ETO 0.001%) and 2) 0.025 mg/g (ETO 0.0025%). Although the chemopreventive effects were not statistically significant, remarkable tumour suppressive effects with the concentration of ETO 0.0025% were recorded. The incidence decreased by 4.31% and tumour frequency per group decreased by 6.67% when compared to the control group. Latency (the period from carcinogen administration to the first tumour appearance) increased by 7.28% in dose-dependent manner. The results of our experiments point to dose-dependent tumour suppressive effects of a higher concentration of etoricoxib (ETO 0.0025%) when compared to the control group. They suggest that higher etoricoxib concentrations may enhance its tumour suppressive effects.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

Effects of Blood Glucose Changes and Physostigmine on Anesthetic Requirements of Halothane in Rats 

1997 ◽  
Vol 87 (2) ◽  
pp. 354-360 ◽  
Author(s):  
Yumiko Ishizawa ◽  
Shuichiro Ohta ◽  
Hiroyuki Shimonaka ◽  
Shuji Dohi
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Minimum Alveolar Concentration ◽  
Severe Hypoglycemia ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Control Value ◽  
Sprague Dawley Rats ◽  
Brain Acetylcholine

Background Although hyper- and hypoglycemia induce neurophysiologic changes, there have been no reports on the effects of blood glucose changes on anesthetic requirements. This study examined the effects of hyper- and hypoglycemia on the minimum alveolar concentration (MAC) of halothane in rats. In addition, based on a previous finding that the level of brain acetylcholine was reduced during mild hypoglycemia, the authors examined the influence of physostigmine on MAC during hypoglycemia. Methods In Sprague-Dawley rats, anesthesia was induced and maintained with halothane in oxygen and air. The MAC was determined by observing the response to tail clamping and tested during mild hypoglycemia (blood glucose level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl) induced by insulin and glucose infusion, respectively (experiment 1). The effects of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl; experiment 2). Results In experiment 1, mild hypoglycemia significantly reduced the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/- 0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg reduced MAC. Conclusions Hypoglycemia reduced anesthetic requirements in a degree-dependent manner, whereas hyperglycemia had no effects. Although the mechanism of hypoglycemic MAC reduction needs further investigations, physostigmine studies suggest that this may not be related to inhibition of cholinergic transmission.

scholarly journals Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad

2018 ◽  
Vol 30 (5) ◽  
pp. 708-714 ◽  
Author(s):  
David C. Dorman ◽  
Melanie L. Foster ◽  
Brooke Olesnevich ◽  
Brad Bolon ◽  
Aude Castel ◽  
...  
Keyword(s):  
Motor Activity ◽  
Polyacrylic Acid ◽  
Muscle Tone ◽  
Clinical Signs ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Acute Neurotoxicity ◽  
Disposable Diapers

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered “nontoxic” with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6–19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

2021 ◽  
Author(s):  
Atta Mohammad Dost ◽  
Mehmet Gunata ◽  
Onural Ozhan ◽  
Azibe Yildiz ◽  
Nigar Vardi ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Kidney Tissue ◽  
Control Group ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Per Oral

Abstract Amikacin (AK) is frequently used in the treatment of gram-negative and some gram-positive infections. However, its use is limited due to nephrotoxicity due to the increase in reactive oxygen radicals. The aim of this study was to investigate the role of carvacrol (CAR) against AK-induced nephrotoxicity in rats. Thirty-two Sprague Dawley rats were randomly divided into four groups as control (Vehicle), AK (400 mg/kg), CAR + AK (80 mg/kg CAR + 400 mg/kg AK), and AK + CAR (400 mg/kg AK + 80 mg/kg CAR) groups. AK and CAR were administered via intramuscular and per-oral for 7 days, respectively. Blood and kidney tissue samples were taken at the end of the experiment. Renal function and histopathological changes were compared, and the relevant parameters of oxidative stress and inflammation were detected. Histopathological findings (necrotic changes and dilatation and inflammatory cell infiltration) significantly increased in the AK group compared to the control group. Also, the rats in the AK group lost weight significantly. It was found that CAR treatment before and after AK significantly improved nephrotoxicity histopathologically (p < 0.05). However, this improvement was not detected biochemically. These results show that CAR treatment before and after AK improves nephrotoxicity in the histopathological level.

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