Delayed Calcium Channel Blockade with Diltiazem Reduces Paracetamol Hepatotoxicity in Mice

1991 ◽  
Vol 10 (2) ◽  
pp. 119-123 ◽  
Author(s):  
Charles D. Deakin ◽  
Christopher D. Gove ◽  
Elizabeth A. Fagan ◽  
J. Michael Tredger ◽  
Roger Williams
Keyword(s):  
Body Weight ◽  
Liver Damage ◽  
High Power ◽  
Aspartate Aminotransferase ◽  
Channel Blockade ◽  
Aminotransferase Activity ◽  
High Power Field ◽  
Calcium Channel Blockade ◽  
Regenerative Activity ◽  
Mitotic Figures

1 Diltiazem (30 mg kg-1 body weight, intraperitoneally) given to mice 9 h after paracetamol (450 mg kg-1, orally) reduced liver damage, as judged by plasma aspartate aminotransferase activity (median 186, range 6-602 IU I-1, n = 18 vs 466, range 23-3872 IU I-1 in 18 saline-treated controls; P < 0.05) with comparable reductions in mortality (14% vs 33%, respectively; NS). 2 Regenerative activity, as judged by mitotic figures in tissue removed at 30 h after paracetamol, was significantly higher in mice treated at 9 h with diltiazem (median 0.83 per high power field vs 0.1 in saline-treated controls; P < 0.05). 3 Diltiazem administered earlier or later than 9 h showed reduced efficacy and in some cases potentiated toxicity, as did nifedipine (40 mg kg-1 in divided doses up to 9 h).

scholarly journals Effect of Terminalia Chebula (Haritaki) on Serum Aspartate Aminotransferase, Alanine Aminotransferase in Paracetemol induced liver damage in Wister Albino Rats

2015 ◽  
Vol 10 (1) ◽  
pp. 1-5
Author(s):  
Tania Yeasmin ◽  
Qazi Shamima Akhter ◽  
Syeda Tasfia Siddika ◽  
Fayeza Karim
Keyword(s):  
Body Weight ◽  
Liver Function ◽  
Liver Damage ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Basal Diet ◽  
Base Line ◽  
Terminalia Chebula ◽  
Serum Aspartate Aminotransferase ◽  
Bonferroni Test

Background: Liver plays a major role in detoxification and excretion of many endogenous and exogenous compounds. Any injury may lead to severe liver damage and impairment of liver function. Harbal plants such as Terminalia chebula (Haritaki) may have free radical scavenging activity thereby can be used for the prevention and treatment of liver damage.Objective: To observe the effect of Terminalia chebula on paracetamol induced changes of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in Wister albino rats.Methods: This experimental study was carried out in the Department of Physiology, Dhaka Medical College, Dhaka from January to December’ 2013. Total 44 rats with age 90 to 120 days, weighing between 150 to 200 gm were selected. After acclimatization for 14 days, they were divided into base line control (BC, n=11), paracetamol treated control (PC, n=11),Terminalia chebula pretreated and paracetamol treated (TCP-PCT n=11) and paracetamol pretreated and Terminalia chebula treated group (PCP-TCT, n=11). All groups received basal diet for 21 consecutive days. In addition to basal diet, rats of BC received propylene glycol (2ml/kg body weight, orally) and PC received single dose of paracetamol suspension (750mg/kg body weight, orally) on 21st day. Rats of TCP-PCT received Terminalia chebula extract (200 mg/kg body weight, orally) for 21 consecutive days and paracetamol suspension (750mg/kg body weight, orally) on 21st day. Again, rats of PCP-TCT received paracetamol suspension (750mg/kg body weight, orally) on the 1st day and Terminalia chebula extract (200 mg/kg body weight orally) for 21 consecutive days. All rats were sacrificed on 22nd day and then blood samples were collected. For assessment of liver function serum AST and ALT levels were estimated by using standard laboratory kits. The statistical analysis was done by one way ANOVA and post hoc Bonferroni test as applicable.Results: The mean serum AST and ALT levels were significantly (p<0.001) higher in PC in comparison to those of BC. Serum AST and ALT levels of all experimental groups were significantly (P<0.001) lower than PC group. Conclusion: From the results of this study, it may be concluded that Terminalia chebula may have some hepatoprotective effects in paracetamol induced liver damage in rats.Bangladesh Soc Physiol. 2015, June; 10(1): 1-5

scholarly journals Computerized Calculation of Mitotic Count Distribution in Canine Cutaneous Mast Cell Tumor Sections: Mitotic Count Is Area Dependent

2019 ◽  
Vol 57 (2) ◽  
pp. 214-226 ◽  
Author(s):  
Christof A. Bertram ◽  
Marc Aubreville ◽  
Corinne Gurtner ◽  
Alexander Bartel ◽  
Sarah M. Corner ◽  
...  
Keyword(s):  
Mast Cell ◽  
High Power ◽  
Ground Truth ◽  
Mitotic Count ◽  
Automated Image Analysis ◽  
High Power Field ◽  
Borderline Cases ◽  
Area Selection ◽  
Cutaneous Mast Cell ◽  
Mitotic Figures

Mitotic count (MC) is an important element for grading canine cutaneous mast cell tumors (ccMCTs) and is determined in 10 consecutive high-power fields with the highest mitotic activity. However, there is variability in area selection between pathologists. In this study, the MC distribution and the effect of area selection on the MC were analyzed in ccMCTs. Two pathologists independently annotated all mitotic figures in whole-slide images of 28 ccMCTs (ground truth). Automated image analysis was used to examine the ground truth distribution of the MC throughout the tumor section area, which was compared with the manual MCs of 11 pathologists. Computerized analysis demonstrated high variability of the MC within different tumor areas. There were 6 MCTs with consistently low MCs (MC<7 in all tumor areas), 13 cases with mostly high MCs (MC ≥7 in ≥75% of 10 high-power field areas), and 9 borderline cases with variable MCs around 7, which is a cutoff value for ccMCT grading. There was inconsistency among pathologists in identifying the areas with the highest density of mitotic figures throughout the 3 ccMCT groups; only 51.9% of the counts were consistent with the highest 25% of the ground truth MC distribution. Regardless, there was substantial agreement between pathologists in detecting tumors with MC ≥7. Falsely low MCs below 7 mainly occurred in 4 of 9 borderline cases that had very few ground truth areas with MC ≥7. The findings of this study highlight the need to further standardize how to select the region of the tumor in which to determine the MC.

Ostensibly ineffectual doses of cadmium and lipopolysaccharide causes liver damage in rats

2010 ◽  
Vol 30 (7) ◽  
pp. 624-635 ◽  
Author(s):  
Periasamy Srinivasan ◽  
Ya-Hui Li ◽  
Dur-Zong Hsu ◽  
Shih-Bin Su ◽  
Ming-Yie Liu
Keyword(s):  
Body Weight ◽  
Liver Damage ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Liver Function Tests ◽  
Hepatic Damage ◽  
Histopathological Analysis ◽  
Liver Histopathology ◽  
Hepatic Lipid Peroxidation ◽  
Hepatic Metallothionein

Various hepatotoxicants co-treated with lipopolysaccharide (LPS) have the potential to cause severe hepatic damage. Whether co-treatment with ostensibly ineffectual (without effect on customary clinical liver function tests, such as aspartate aminotransferase and alanine aminotransferase) doses of cadmium (Cd) and LPS cause liver damage is still unknown. We examined the effects of treating ostensibly ineffectual doses of Cd and LPS on liver dysfunction as well as on liver histopathology. We injected rats with saline only, Cd only, LPS only, or a single ostensibly ineffectual dose of Cd (100 μg/kg body weight) plus LPS (0.1 mg/kg body weight). After 6 h, the rats were killed and their liver damage was assessed. Co-treated with ostensibly ineffectual doses of Cd and LPS had higher levels of aspartate aminotransferase and alanine aminotransferase, hepatic lipid peroxidation, peroxynitrite, nitrite, and interleukin-1β (IL-1β), but lower levels of hepatic metallothionein (MT) than did that treated with saline only, Cd only, and LPS only. Histopathological analysis of Cd only and LPS only showed apparent liver damage, but Cd plus LPS showed marked hepatic damage. We conclude that co-treating the rats with ostensibly ineffectual doses of Cd and LPS is hepatotoxic. Cd promotes LPS-initiated oxidative-stress-associated liver damage by increasing IL-1β and decreasing MT levels in rats.

Enhanced vasodilatation in essential hypertension by calcium channel blockade with verapamil

Hypertension ◽  
1982 ◽  
Vol 4 (3) ◽  
pp. 26-31 ◽  
Author(s):  
U. L. Hulthen ◽  
P. Bolli ◽  
F. W. Amann ◽  
W. Kiowski ◽  
F. R. Buhler
Keyword(s):  
Essential Hypertension ◽  
Calcium Channel ◽  
Channel Blockade ◽  
Calcium Channel Blockade

scholarly journals Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 41
Author(s):  
Nouf Aljobaily ◽  
Michael J. Viereckl ◽  
David S. Hydock ◽  
Hend Aljobaily ◽  
Tsung-Yen Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Methylation ◽  
Body Weight ◽  
Liver Fibrosis ◽  
Liver Damage ◽  
Cellular Senescence ◽  
Weight Ratio ◽  
Mrna Levels ◽  
Body Weight Ratio ◽  
Chromosomal Stability

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

scholarly journals Is There Pathological Uniformity between the Periphery and Center of a Gastrointestinal Stromal Tumor?

2021 ◽  
Vol 10 (4) ◽  
pp. 687
Author(s):  
Seong Ji Choi ◽  
Kwan Hong Lee ◽  
Chan Kyoo Yoo ◽  
Jai Hoon Yoon ◽  
Ki Seok Jang ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Mitotic Index ◽  
High Power ◽  
Malignant Potential ◽  
Mitotic Count ◽  
Pathological Diagnosis ◽  
High Power Field ◽  
Gastric Gists ◽  
Significant Difference ◽  
The Mean

Background: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and have some malignant potential. Mitotic count is important for predicting the malignant potential of GISTs. Proper treatment of GISTs requires accurate pathological diagnosis. In general, endoscopic ultrasound-guided fine-needle aspiration and deep biopsy are used for pathological diagnosis of GIST before making decisions about surgery. This study sought to evaluate the pathological uniformity of gastric GISTs for mitotic index of the center and periphery of the GIST. Methods: We retrospectively reviewed the data of 37 gastric GIST patients who underwent wedge resection at Hanyang University Hospital. We used Armed Forces Institute of Pathology criteria to classify gastric GISTs. To determine the pathological uniformity of gastric GISTs, we compared GIST risk stratification between the center and periphery of GISTs. Results: The mean size of GISTs was 3.56 ± 2.10 cm. Three lesions were located in the antrum, 11 in the fundus, 9 in the cardia, and 14 in the body. The mean age of patients was 58.65 ± 9.44 years; 18 patients were male and 19 were female. Thirty-five patients (94.6%) showed the same level of risk stratification between the center and periphery of gastric GISTs, while two patients (5.4%) presented different levels of risk between the two sites. No significant difference in mitotic count was observed between the two sites (kappa value = 0.863; p = 0.001). Conclusions: Mitotic index category (either more than five mitoses per high-power field or five or fewer mitoses per high-power field) of GISTs showed good concurrence between the center and periphery.

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