scholarly journals Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Star Khoza ◽  
Ishmael Moyo ◽  
Denver Ncube
Keyword(s):  
Liver Injury ◽  
Hepatic Injury ◽  
Antifungal Agents ◽  
Liver Enzymes ◽  
Control Group ◽  
Poor Correlation ◽  
Histopathological Changes ◽  
Increased Risk ◽  
The Subject ◽  
Oral Doses

Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p=0.0017) and AST levels (p=0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p<0.0001). The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

scholarly journals STANDARDIZATION OF MODEL OF INDUCTION OF HEPATOTOXICITY WITH ANTI-TUBERCULOSIS DRUGS IN WISTAR ALBINO RATS

2017 ◽  
Vol 10 (6) ◽  
pp. 150
Author(s):  
Sarita M Kapgate ◽  
Abhijit B Patil
Keyword(s):  
Liver Injury ◽  
Animal Studies ◽  
Hepatic Injury ◽  
Albino Rats ◽  
Histopathological Changes ◽  
First Line ◽  
Drug Induced ◽  
Significant Development ◽  
Reported Study ◽  
Wistar Albino Rats

Objective: The objective of the study to standardize the model of hepatotoxicity induced by ATT drugs in Wistar Albino rats. Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), the first line drugs used in the treatment of tuberculosis (TB) associated with the potential adverse effect. Numerous animal studies were reported endeavoring induction and cure of anti-TB (ATT) drug-induced hepatotoxicity using herbal and chemical drugs. However, the previous reported study failed to replicate where Wistar albino rats were treated with INH, RMP, and PZA and had shown the significant development of liver injury. Hence in present paper, aimed to develop a standardize model of induction of hepatotoxicity with ATT drugs.Methods: Wistar rats were treated with ATT drugs in combination in various doses up to 4-8 weeks. Total nine experiments were conducted to achieve successful hepatotoxicity. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were the biochemical parameters of assessment. Histopathological changes in the liver were also examined.Results: No evidence of any liver injury or an inflammatory infiltrate has been observed as had been reported in the previous studies. Rather decrease in serum ALT levels has been observed by researcher. In short, hepatic injury cannot be developed with the doses used in previous reported papers. The successful attempt to induce hepatotoxicity can be achieved with the doses of INH - 100, RMP - 300, PZA - 700 mg/kg. The findings were confirmed by the raised ALT, AST, and ALP levels compared with baseline. The histopathological changes also support the findings.Conclusion: The dose of INH - 100, RMP – 300 and PZM - 700 mg/kg. Succeeds to induce hepatotoxicity in Wistar albino rats and Swiss albino mice as well.

scholarly journals Aloperine attenuates carbon tetrachloride-induced mouse hepatic injury via Nrf2/HO-1 pathway

2020 ◽  
Vol 19 (5) ◽  
pp. 983-988
Author(s):  
Rui Xiong ◽  
Shuzhong Shan ◽  
Xiaoming Wang ◽  
Xiaowen Zhang ◽  
Haixia Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Control Group ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Oxidative Stress Biomarkers ◽  
Cox 2

Purpose: To investigate whether aloperine pretreatment ameliorates acute liver injury in carbon tetrachloride (CCl4)-treated mice.Methods: Mice were injected with CCl4 and orally administered aloperine. Blood samples and liver tissues were used for histopathological and biochemical analyses, respectively. Protein expression levels were determined by western blotting.Results: Histopathological analysis indicate that aloperine pretreatment significantly alleviated CCl4- induced mouse hepatic injury. CCl4 treatment induced the upregulation of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine amino transferase (ALT), and total bilirubin (p < 0.05). However, these alterations were significantly inhibited by aloperine treatment. Moreover, aloperine pretreatment markedly decreased (p < 0.05) the CCl4-induced expression of oxidative stress biomarkers, including malondrialdeline (MDA), glutathione (GSH), catalase (CAT), and  superoxide dismutase (SOD). Compared to the control group, the protein levels of Nrf2, HO-1, iNOS, and COX-2 were significantly increased in the CCl4 group, while Nrf2 and HO-1 were upregulated. Furthermore, iNOS and COX-2 were downregulated in mouse liver in CCl4 + aloperine group compared to CCl4 group in a concentration-dependent manner (p < 0.05).Conclusion: Aloperine pretreatment appears to markedly upregulate Nrf2 and HO-1 and downregulate iNOS and COX-2 to suppress hepatic injury in mice. Thus, aloperine is a promising treatment for acute liver injury. Keywords: Hepatic injury, Aloperine, Oxidative stress, Nrf2/HO-1 pathway

scholarly journals HEPATOTOXICITY OF DOXYCYCLINE: BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN RABBITS

1969 ◽  
Vol 1 (1) ◽  
pp. 16-20
Author(s):  
HajiAkbar ◽  
S. M.Naeem ◽  
S.Mutahir Ali Shah ◽  
Alamzeb ◽  
Ayaz Ali Khan ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Dose Rate ◽  
Untreated Control ◽  
Significant Rise ◽  
Control Group ◽  
Histopathological Changes ◽  
Control Serum ◽  
Oral Doses ◽  
Group D ◽  
Postmortem Examinations

Background: To study the degree of hepatotoxicity of Doxycycline molecule on the basis of biochemicaland histopathological changes in the serum/liver of rabbits at different doses.This descriptive and analytic study was conducted in the Department of Biotechnology, University ofMalakand, Dir and Department of Biochemistry, SMC,Swat.Matterial And Methods:Different oral doses of doxycycline were administered to healthy rabbits, dividedin to six groups A, B, C, D, E & F. The strength of the dose was kept as 10, 20, 40, 80, & 100 mg/kg bodyweight for four consecutive days respectively, while the group F was kept as untreated control. Serum ALTlevels were measured at 1st, 4,h, 8th, & 12th post medicated days to evaluate degree of hepatotoxicity. Postmortem examinations of all groups were performed at the end of experiment.Results: Significant rise in ALT was observed in all treated subjects as compared to un-treated control(group F). The maximum ALT levels were found in group D & E medicated at dose rate of 80 mg/kg of bodyweight & 1OOmg/kg of baody weight, respectively. High mortality rate occurred in treated groups; GroupD and Group E were 25% and 50%, respectively. Histopathological changes occurring in the liver of treatedgroups were observed in thestudy.Conclusion: It is concluded from this study that the degree of hepatotoxicity increases as the doxycyclinedose increases.This issupported both by biochemical derangement as well as histopathological study.Keywords: Doxycycline,AlanineAminotransf-erase (ALT), toxicity, rabbits

scholarly journals STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY

1925 ◽  
Vol 42 (1) ◽  
pp. 99-122 ◽  
Author(s):  
Robert Elman ◽  
Philip D. McMaster
Keyword(s):  
Liver Injury ◽  
Biliary Obstruction ◽  
Intestinal Tract ◽  
Hepatic Injury ◽  
Common Duct ◽  
Bile Pigment ◽  
Uninfected Animal ◽  
Place Of Origin ◽  
The Subject ◽  
The Common

A variety of evidence is presented, all of which supports the view that in the uninfected animal the intestinal tract is the only place of origin of urobilin, not merely under normal circumstances, but when there is biliary obstruction. Animals rendered urobilin-free by collection of all of the bile from the intubated common duct remain urobilin-free even after severe hepatic injury. In our experiments urobilinuria was never found after liver damage except when bile pigment was present in the intestine. Thus, for example, it appeared during the first days after Ugation of the common duct, but disappeared as the stools became acholic. When this had happened a small amount of urobilin-free bile, given by mouth, precipitated a prompt urobilinuria. After obstruction of the duct from one-third of the liver, mild urobilinuria was found, but no bilirubinuria. In animals intubated for the collection of a part of the bile only, while the rest flowed to the duodenum through the ordinary channels, liver injury caused urobilinuria, unless indeed it was so severe as to lead to bile suppression, when almost at once the urobilinuria ceased, though the organism became jaundiced. The evidence here presented, when taken with that of our previous papers, clearly proves that urobilinuria is an expression of the inability of the liver cells to remove from circulation the urobilin brought by the portal stream, with result that the pigment passes on to kidney and urine. Urobilinuria occurs with a far less degree of liver injury than does bilirubinuria. Our work has, for the most part, been carried out with animals having uninfected livers and bile passages. But the influence of cholangitis with infection has been briefly discussed in the light of some preliminary observations. The influence of infection on the place of formation of urobilin and on the occurrence of urobilinuria will form the subject of another communication.

Pro-oxidant effects of a high α-tocopherol dose on kidney antioxidant biomarkers and histopathological aspects

2017 ◽  
Vol 87 (3-4) ◽  
pp. 179-190
Author(s):  
Amel Kanane ◽  
Fayrouz Rouaki ◽  
Mohamed Brahim Errahmani ◽  
Abdenour Laraba ◽  
Hayet Mesbah ◽  
...  
Keyword(s):  
Sunflower Oil ◽  
Antioxidant Status ◽  
Basal Diet ◽  
Inflammatory Cells ◽  
Significant Rise ◽  
Control Group ◽  
Histopathological Changes ◽  
Group 5 ◽  
Oxidant Effect ◽  
Higher Doses

Abstract. The aim of this study is to evaluate the effect of α-tocopherol supplementation at two doses (600 and 1200 mg × kg–1) on kidney antioxidant status and the histopathological changes in Wistar rats after 12 weeks of exposure at different diets. Forty rats has been divided into 4 groups of 10 rats each, the control group received basal diet with 5 % fresh sunflower oil (FSO), the second group: 5 % oxidized sunflower oil (OSO), the third group: 5 % OSO supplemented with 600 mg × kg–1 α-tocopherol and the fourth group: 5 % OSO supplemented with 1200 mg × kg–1 α-tocopherol. In OSO groups, the results showed highly significant increases of LPO (from 31.3 ± 0.9 to 53.8 ± 1.2 nmol of MDA formed/min/mg protein, p < 0.0001) with a significant decrease (p < = 0.001) of the antioxidant enzymatic activities (CAT, SOD, GPX, GR and G6PDH), body weight (339 ± 9 to 290 ± 3 g) and α-tocopherol levels (13.6 ± 0.6 to 6.5 ± 0.4 μg/mg protein). In OSO groups with 600 mg × kg–1 α-tocopherol, an antioxidant effect was found, reflected by a return of the parameters to values similar to those of the control group. However, higher doses of α-tocopherol (1200 mg × kg–1) induced a depletion of antioxidant status, α-tocopherol levels (6.0 ± 0.3 μg/mg protein, p < 0.001) and a very highly significant rise (p < 0.0001) of LPO content (54.86 ± 0.01 nmol of MDA formed/min/mg protein). The kidney tissues also showed changes in glomerular, severe inflammatory cells infiltration, and formation of novel vessels. So, we can conclude that the oxidative stress is attenuated by a moderate administration of 600 mg × kg–1 α-tocopherol, while a pro-oxidant effect occurs at 1200 mg × kg–1 α-tocopherol.

Overtraining of aerobic physical exercise reduce rats (Rattus norvegicus) memory

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ni Made Ridla Parwata
Keyword(s):  
Body Weight ◽  
Physical Exercise ◽  
Rattus Norvegicus ◽  
Research Method ◽  
Male Rat ◽  
Control Group ◽  
Adult Male Rat ◽  
The Subject ◽  
Heavy Training

Overtraining syndrome is a decrease in physical capacity, emotions and immunity due to training that is too often without adequate periods of rest. Overtraining is often experienced by athletes who daily undergo heavy training with short break periods. This research aims to look at the effect of overtraining aerobic physical exercise on memory in mice. The research method was experimental in vivo with the subject of adult male rat (Rattus Norvegicus) Winstar strain aged 8-10 weeks, body weight 200-250 gr. Divided into three groups, namely the control group, aerobic group and overtraining group. The results of memory tests with water E Maze showed an increase in the duration of travel time and the number of animal errors made by the overtraining group (p = 0.003). This study concludes that overtraining aerobic physical exercise can reduce memory in rat hippocampus.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

Pathological features of the sequence in pregnant women with delayed fetal growth

2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  
Keyword(s):  
Pregnant Women ◽  
Intrauterine Growth Restriction ◽  
Normal Development ◽  
Intrauterine Infection ◽  
Normal Pregnancy ◽  
Growth Restriction ◽  
Control Group ◽  
Intrauterine Growth ◽  
Increased Risk ◽  
Infection And Inflammation

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.

THE EFFECT OF APPLYING DEMONSTRATION METHOD ON STUDENTS’ ACHIEVEMENT IN SPEAKING SKILL AT THE THIRD GRADE OF SMK PAB 3 MEDAN ESTATE

2015 ◽  
Vol 4 (2) ◽  
Author(s):  
Meryanti Napitupulu And Anni Holila Pulungan
Keyword(s):  
High School ◽  
Control Group ◽  
Vocational High School ◽  
Control Groups ◽  
Speaking Test ◽  
The Third ◽  
Speaking Skill ◽  
The Subject ◽  
And Control ◽  
Experimental Group

This study was conducted as an attempt to discover the effect of applying Demonstration Method on students’ achievement in speaking skill. It was an experimental research. The subject was students of Grade XII, Vocational High School (Sekolah Menengah Kejuruan: SMK), which consisted of 79 students. The research was divided into two groups: experimental and control groups. The instrument used to collect the data was speaking test. To obtain the reliability of the test, the writer applied Kuder Richardson 21 formula. The result of the reliability was 0.7, and it was found that the test was reliable. The data were analyzed by using t-test formula. The analysis showed that the scores of the students in the experimental group were significantly higher than the scores of the students in the control group at the level of significant m = 0.05 with the degree of freedom (df) 77, t-observed value 8.9 > t-table value 1.99. The findings indicate that using Demonstration Method significantly affected the students’ achievement in speaking skill. So, English teachers are suggested to use Demonstration Method in order to improve students’ achievement in speaking skill.

Employing Gamma Ray Irradiated Giardia lamblia as Trialed Vaccine in Experimental Animal

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Amal Kamil Abdul Sada ◽  
Amany Mohamed Al-Kaysi
Keyword(s):  
Giardia Lamblia ◽  
Gamma Ray ◽  
Age Groups ◽  
Active Phase ◽  
Study Groups ◽  
Negative Control ◽  
Control Group ◽  
High Dose ◽  
Histopathological Changes ◽  
Gamma Irradiated

This is an experimental trial to prepare a vaccine from gamma-irradiated Giardia lamblia which is evaluated in experimental animals. The study was conducted from December 2015 to April 2016. The field survey of the parasite was conducted from those patients attending the laboratories of the Alawi Children's Hospital in Rusafa and the Al-Yarmouk Teaching Hospital in Karkh, through which 1250 stool samples of different age groups were examined. Five groups of mice were used in the study; the first was injected with normal saline and considered as a negative control group, the second was injected with cystic form of non-irradiated Giardia lamblia and considered as a positive control group, whereas the other three groups were injected with gamma irradiated Giardia lamblia at three different doses 10, 15 and 25 rad respectively. Giardia lamblia was primarily cultivated in liver infusion agar for ten days to obtain the active phase. On the sixth day, the cystic phase was purified and standardized to be used in the infection of mice with or without the exposure of gamma rays. Mice showed high sensitivity to parasitic infestation, in the gamma non-irradiated and the irradiated with gamma 10 rad, and 15 rad irradiated groups which was 100%. The results expressed an excystation process of the depleted phases and the release of the feeder phases. The results of the three irradiated groups consisted of histopathological changes of the small, and the rectum by dissection after two weeks of infection, with intestine amputation lesions, as well as ulceration and inflammation of the inflammatory cells represented in small numbers of neutrophil, lymphocytes, and eosinophils. The presence of ulceration and fall of epithelial cells in the intestinal cavity has been shown, and different forms of the parasite have been observed. Mice which was injected with irradiated G lamblia at high dose (25 rad), not show and sensitivity to the challenge infection and no excystation of thy parasite had been done. After 2 wreaks, a comparison was achieved between all study groups in which no histopathological changes were noticed in the mice irradiated with dose of25 rad. After another two weeks, a challenge dose was given (un-attenuated G lamblia) and mice were dissected after another two weeks, no changes on the level of histopathology of intestinal tissue were noticed the results suggested that mice acquire an immunity against the parasite infection.

Sign in / Sign up

Export Citation Format

Share Document