Seizure vulnerability and anxiety responses following chronic co-administration and acute withdrawal of caffeine and ethanol in a rat model

2018 ◽  
Vol 29 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Daniel Matovu ◽  
Paul E. Alele
Keyword(s):  
Low Dose ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Untreated Control Group ◽  
Acute Withdrawal ◽  
Plus Maze ◽  
Significant Difference ◽  
Global Increase ◽  
Withdrawal Effects

AbstractBackground:Caffeine antagonizes the intoxicating effects of alcohol. Consequently, there has been a dramatic global increase in the consumption of caffeinated drinks together with alcohol, especially among young adults. We assessed the seizure vulnerability and anxiety responses following the chronic co-administration of, and withdrawal from, caffeine and ethanol in male rats.Methods:The rats were randomly assigned to six groups consisting of 10 animals each: 10 mg/kg of caffeine, 20 mg/kg of caffeine, 4 g/kg of 20% ethanol, combined caffeine (20 mg/kg) and ethanol (4 g/kg of 20%), 4 mL/kg distilled water, and an untreated control group. The test substances were administered intragastrically twice daily for 29 days. On day 29, the rats were tested on the elevated plus maze to assess anxiety-related responses. On day 30, pentylenetetrazol (PTZ), a chemoconvulsant, was administered intraperitoneally at a dose of 40 mg/kg to the animals. Seizure responses and mortality up to 72 h were recorded.Results:Compared with the control group, the rats that received chronic treatment with low-dose caffeine, ethanol alone, and combined caffeine and ethanol exhibited significant anxiogenic-like effects, unlike with high-dose caffeine. Both low- and high-dose caffeine significantly increased PTZ seizure latency. Ethanol alone and combined caffeine and ethanol both lowered PTZ seizure latency. No significant difference occurred between the controls and the untreated group for either anxiety or seizure expression. Combined caffeine and ethanol increased the seizure-induced mortality from withdrawal effects at 72 h.Conclusions:These findings suggest that the chronic co-administration of caffeine and ethanol and the acute withdrawal from these drugs lead to anxiogenic effects and increased seizure vulnerability.

scholarly journals SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

2016 ◽  
Vol 9 (5) ◽  
pp. 197
Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  
Keyword(s):  
Liver Function ◽  
Toxicity Test ◽  
Low Dose ◽  
Ethanol Extract ◽  
Good Effect ◽  
Control Group ◽  
High Dose ◽  
Subchronic Toxicity ◽  
Treatment Groups ◽  
Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

scholarly journals Enhanced intestinal 2-deoxy-2-[18F]fluoro-D-glucose uptake under metformin is not fully suppressed by loperamide

2018 ◽  
Vol 52 (4) ◽  
pp. 185-191
Author(s):  
Tomomi Nobashi ◽  
Tsuneo Saga ◽  
Yuji Nakamoto ◽  
Yoichi Shimizu ◽  
Sho Koyasu ◽  
...  
Keyword(s):  
Body Weight ◽  
Small Intestine ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Fdg Uptake ◽  
Significant Difference ◽  
Mouse Small Intestine ◽  
Long Acting ◽  
And Control

AbstractObjective. This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. Methods. Mean18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. Results.18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. Conclusion. Metformin increased18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of18F-FDG.

Influence of doxorubicin on lipid peroxidation and heart histology in rats

2015 ◽  
Vol 21 (31) ◽  
pp. 33-36
Author(s):  
Джиоев ◽  
Inal Dzhioev ◽  
Джанаев ◽  
Robert Dzhanaev
Keyword(s):  
Low Dose ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Cardiovascular Toxicity ◽  
Anthracycline Antibiotic ◽  
Cross Striation ◽  
Group A ◽  
Sexually Mature ◽  
Experimental Group

Anthracycline antibiotic doxorubicin, which has proven cardiovascular toxicity, is often used in the treatment of cancer. The research project was carried out in 21 sexually mature Wistar male rats divided into three groups: control group, high-dose experimental group, in which rats were once injected intraperitoneally with doxorubicin hydrochloride at a dose of 10 mg/kg and low-dose experimental group, in which animals twice received intraperitoneal 2.5 mg/kg doses of doxorubicinhydrochloride at 10-day interval.An increase of malondialdehyde was revealed in the membranes of red blood cells in the high-dose experimental group, while in the low-dose experimental group a reduction in the levels of malondialdehyde and plasma hydroperoxides as well as a decreasing of catalase activity was observed. Intake of doxorubicin also causes venous hyperemia in wide areas of myocardiumalong with increasing of cardiomyocytic cross striation.

Blood Pressure Lowering Effect of Korea Ginseng Derived Ginseol K-g1

2014 ◽  
Vol 42 (03) ◽  
pp. 605-618 ◽  
Author(s):  
Moo-Yong Rhee ◽  
Belong Cho ◽  
Kwang-Il Kim ◽  
Joohee Kim ◽  
Mi Kyung Kim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Low Dose ◽  
Favorable Effect ◽  
Control Group ◽  
High Dose ◽  
Blood Pressure Lowering Effect ◽  
Clinical Trial Registration ◽  
Ginseng Extract ◽  
Treatment Groups ◽  
Significant Difference

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov , identifier: NCT01483430.)

High-Dose Glucocorticoids Inhibit Proliferation of Rat Olfactory Epithelium

2002 ◽  
Vol 111 (10) ◽  
pp. 909-911 ◽  
Author(s):  
Yasushi Ohta ◽  
Nobuko Marino ◽  
Minako Takanosawa ◽  
Shinichi Ishimoto ◽  
Chiori Matumoto ◽  
...  
Keyword(s):  
Growth Factors ◽  
Olfactory Epithelium ◽  
Olfactory Dysfunction ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Proliferating Cells ◽  
Subcutaneous Dose ◽  
Significant Difference ◽  
The Mean

Glucocorticoids (GCs) are commonly prescribed for treatment of olfactory dysfunction. However, the effects of GCs on olfactory epithelium are not well known. We investigated the effects of high-dose GCs on proliferating cells of olfactory epithelium. Five adult male rats (300 g) received a single daily subcutaneous dose of vehicle containing 0.3 mg dexamethasone (DEX) for 9 days (DEX+ group), and a control group received vehicle alone (DEX– group). We compared sections from the Two groups for numbers of Ki67-positive cells. The mean number of Ki67-positive cells per 500 olfactory epithelial cells was 9.6 for the DEX+ group and 58 for the DEX– group (significant difference). We conclude that high-dose GC suppressed proliferation of olfactory epithelium. We suggest that high-dose GC suppresses cytokines and growth factors, resulting in secondary suppression of proliferating ability.

Gender difference in arsenic biotransformation is an important metabolic basis for arsenic toxicity

2021 ◽  
Author(s):  
Maihaba Muhetaer ◽  
Mei Yang ◽  
Rongxiang Xia ◽  
Jun Wu
Keyword(s):  
Gender Differences ◽  
Dose Group ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Arsenic Toxicity ◽  
Male And Female ◽  
Significant Difference ◽  
Medium Dose

Abstract Background: There are gender differences in the biotransformation of arsenic. We investigated the effects of gender differences on arsenic metabolism and arsenic toxicity mechanisms in rat liver tissues. Methods: Rats were treated with different amounts of arsenic compounds. Arsenic form MMA and DMA in the liver was determined by high performance liquid chromatography-hydride generation atomic fluorescence spectroscopy. SAM, ARR, NAD, PNP, PK, and MPO in rat liver were determined by enzyme-linked immunoassay. RT-qPCR was used to determine AS3MT in the liver. Results: Compared with male and female animals in the same group, MMA and DMA were statistically significant in the three groups of iAs3 + high, iAs3 + medium and iAs5+ low (P <0.05). The MMA of male rats in iAs3+ high and medium groups was higher than that of female rats, and the DMA of male rats was lower than that of female rats. As3MT mRNA in the male iAs3+ high group was higher than that of females. Besides, compared between male and female, only in iAS3+ low dose, iAS3+ medium dose, iAS5+ low dose, and iAS5+ medium dose groups, there was significant difference in SAM level (P<0.05). Compared with male and female animals in the same group, male rats had significantly higher PNP and ARR activities while lower PK activity than female rats (P<0.05). Between the male and female groups, only the iAS3+ high dose and medium dose group had a statistically significant difference (P<0.05). The NAD activity of females in iAS3+ high dose group was higher than that of males. Conclusion: Conclusively, under the same arsenic exposure, there were gender differences between female and male rats, and arsenic metabolism was more cytotoxic to male rats than to females.

scholarly journals The effect of red wine extract, resveratrol, on the degree and rate of orthodontic tooth movement in guinea pigs

2015 ◽  
Vol 5 ◽  
pp. 181-189
Author(s):  
Isidro Alex C. Urriquia ◽  
Lotus D. Llavore
Keyword(s):  
Guinea Pigs ◽  
Low Dose ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Control Group ◽  
High Dose ◽  
Male Adult ◽  
Significant Difference ◽  
The Mean ◽  
And Control

ObjectiveAn animal trial, its protocol approved by the Institutional Animal Care and Use Committee of the U.P. National Institutes of Health (IACUC Protocol No. 2010-008), was employed to investigate the effects of resveratrol on the degree and rate of orthodontic tooth movement in guinea pigs.Materials and MethodsEighteen male adult guinea pigs were randomly allocated into 3 groups: low dose, high dose, and control groups. A 0.016″ titanium molybdenum alloy wire formed into a helical torsion spring with a coil, with the loops cemented onto the maxillary incisors of the animals, served as the orthodontic appliance. Daily oral administration of resveratrol was provided to the low dose (0.047 mg/kg) and high dose (0.47 mg/kg) groups, while water was provided to the control group. Measurements were taken everyday at the interproximal area at the level of the incisal edge using a measuring caliper.ResultsThe results of the ANOVA showed no statistically significant differences in the mean measurements of tooth separation among the three groups from day 2 (P=0.966) to day 8 (P=0.056). However, starting from day 9 (P=0.049) until day 18 (P=0.000), there was a significant difference in the mean tooth separation among the test groups.ConclusionUsing the LSD, it was noted that the low dose and the high dose groups have similar degrees of mean tooth separation, with the control group being significantly different from the two.

Multi-Organ Carcinogenicity of 3,3′-Dimethoxybenzidine Dihydrochloride Given in Drinking Water to F344/N Rats

1990 ◽  
Vol 9 (1) ◽  
pp. 79-91 ◽  
Author(s):  
D. L. Morgan ◽  
J. R. Bucher ◽  
J. E. Huff ◽  
J. K. Haseman ◽  
S. L. Eustis ◽  
...  
Keyword(s):  
Drinking Water ◽  
Human Exposure ◽  
Dose Group ◽  
Chronic Toxicity ◽  
Low Dose ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Human Carcinogen ◽  
Clitoral Gland

3,3′-Dimethoxybenzidine dihydrochloride (DMOB) was evaluated for chronic toxicity and carcinogenicity because benzidine, a structurally related chemical, is a known human carcinogen, and because of potential human exposure during production of bisazobiphenyl dyes. Previous carcinogenicity studies of DMOB were considered to be inadequate. Toxicology and carcinogenesis studies were conducted by administering 0,80,170, or 330 ppm DMOB (>97.5% purity) in drinking water to groups of F344/N rats for 21 months. Seventy rats of each sex were used in the control group, 45 in the low-dose, 75 in the mid-dose, and 70 in the high-dose group. Ten rats of each sex in the control and 330 ppm dose groups were evaluated after 9 months. After exposure for 9 months, chemical-related neoplastic effects included liver foci, carcinoma of the preputial gland in one male, carcinoma of the clitoral gland in one female, and carcinoma of the Zymbal gland in two male rats. Although designed for 24 months, these studies were terminated at 21 months because significant numbers of exposed rats died with tumors or were sacrificed in moribund condition. Chemical-related nonneoplastic effects were hematopoietic cell proliferation in the spleen, and cystic and centrilobular degeneration and necrosis of the liver. 3,3′-Dimethoxybenzidine was clearly carcinogenic for male and female F344/N rats. After exposure for up to 21 months, significantly increased incidences of neoplasms were observed in multiple sites: skin, Zymbal gland, preputial and clitoral glands, oral cavity, small and large intestines, liver, brain, mesothelium, mammary gland, and uterus of treated rats.

scholarly journals An Investigation Into the Beneficial Effects of High-Dose Interferon beta 1-a, Compared to Low-Dose Interferon Beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19

2021 ◽  
Author(s):  
Ilad Alavi Darazam ◽  
Firouze Hatami ◽  
Mohammad Mahdi Rabiei ◽  
Mohamad Amin Pourhoseingholi ◽  
Minoosh Shabani ◽  
...  
Keyword(s):  
Low Dose ◽  
Interferon Beta ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Research Committee ◽  
Subcutaneous Injections ◽  
Beneficial Effects ◽  
Significant Difference ◽  
And Control

Abstract Introduction: Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-β 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high-dose IFN-β 1a compared to low dose IFN-β 1a in moderate to severe COVID-19 cases.Methods: In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high-dose IFN-β 1a (Recigen) (Subcutaneous injections of 88μg (24,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) and the control group was treated with low-dose IFN-β 1a (Recigen) (Subcutaneous injections of 44μg (12,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally, in two groups). Result: A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low-dose IFN-β1a was shorter than that for cases treated with high-dose IFN-β1a (6 vs10 days). Due to differences between some baseline clinical factors between intervention and control group, we performed an adjusted analysis. The model failed to reach a significant difference between two groups. Conclusion: The use of high-dose IFN-β 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it did not have any significant effect on mortality reduction compared with treating with low-dose IFN-β 1a.Trial registration: The trial was confirmed by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences. Signed informed consents were obtained from all the participants or their legally authorized representatives. This trial has been registered as ClinicalTrials.gov, NCT04521400.

Oral administration of Lactobacillus paracasei alleviates clinical symptoms of colitis induced by dextran sulphate sodium salt in BALB/c mice

2014 ◽  
Vol 5 (3) ◽  
pp. 315-322 ◽  
Author(s):  
T. Pan ◽  
H.Y. Guo ◽  
H. Zhang ◽  
A.P. Liu ◽  
X.X. Wang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Low Dose ◽  
Lactobacillus Paracasei ◽  
Control Group ◽  
High Dose ◽  
Intestinal Damage ◽  
Dextran Sulphate ◽  
Dextran Sulphate Sodium ◽  
Tnf Α ◽  
Significant Difference

The aim of this study was to investigate the alleviating effect of Lactobacillus paracasei subsp. paracasei LC-01 (LC-01) on the murine model of colitis induced by dextran sulphate sodium (DSS). 50 pathogen-free, 6-week-old male BALB/c mice were divided randomly into 5 groups, including a control group and four DSS-LC-01-treated groups (DSS, DSS-106, DSS-108, and DSS-1010 with 0, 1×106, 1×108 and 1×1010 cfu/ml LC-01, respectively). To test the effectiveness of LC-01 as a prophylactic it was administered for 7 days before the onset of the disease in DSS-LC-01-treated mice. After 7 days, colitis was induced by administration of 2.5% (w/v) DSS in drinking water for a further 7 days. The disease activity index (DAI), histological score, myeloperoxidase (MPO) activity and the level of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α) were measured. DAI, histological scores and MPO activity of mice treated with a medium or high dose of LC-01 were significantly lower compared to a low-dose of LC-01 and DSS treatment alone (P<0.05). Colon length shortening could be prevented with increasing dose of LC-01. In addition, the levels of IL-1β and TNF-α were suppressed significantly by treatment with a medium and high dose of LC-01. However, no significant difference in the indices mentioned above were observed between a low dose of LC-01 and treatment with DSS alone (P≯0.05). An appropriate dose of LC-01 can prevent intestinal damage in mice with DSS-induced colitis. The expression of inflammatory cytokines related to pathogenesis of DSS-induced colitis decreased following treatment with LC-01.

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