scholarly journals Sex-Linked Differences in the Course of Thioacetamide-Induced Acute Liver Failure in Lewis Rats

2020 ◽  
pp. 835-845
Author(s):  
E KOBLIHOVÁ ◽  
Iveta MRÁZOVÁ ◽  
Z VAŇOURKOVÁ ◽  
H MAXOVÁ ◽  
M RYSKA ◽  
...  
Keyword(s):  
Survival Rate ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Female Rats ◽  
Male Rats ◽  
Preclinical Studies ◽  
Preclinical Research ◽  
Lewis Rats ◽  
General Terms

Acute liver failure (ALF) is a clinical syndrome with high mortality rate, resulting from widespread hepatocyte damage. Its pathophysiological background is still poorly understood and preclinical studies evaluating pathophysiology and new potential therapeutic measures are needed. The model of ALF induced by administration of thioacetamide (TAA) in Lewis rats is recommended as optimal; however, the limitation of previous studies was that they were performed predominantly in male rats. In view of the growing recognition that sex as a biological variable should be taken into consideration in preclinical research, we examined its role in the development of TAA-induced ALF in Lewis rats. We found that, first, intact male Lewis rats showed lower survival rate than their female counterparts, due to augmented liver injury documented by higher plasma ammonia, and bilirubin levels and alanine aminotransferase activity. Second, in female rats castration did not alter the course of TAA-induced ALF whereas in the male gonadectomy improved the survival rate and attenuated liver injury, reducing it to levels observed in their female counterparts. In conclusion, we found that Lewis rats show a remarkable sexual dimorphism with respect to TAA-induced ALF, and male rats display dramatically poorer prognosis as compared with the females. We showed that testosterone is responsible for the deterioration of the course of TAA-induced ALF in male rats. In most general terms, our findings indicate that in the preclinical studies of the pathophysiology and treatment of ALF (at least of the TAA-induced form) the sex-linked differences should be seriously considered.

scholarly journals Hepatocyte Transplantation Attenuates the Course of Acute Liver Failure Induced by Thioacetamide in Lewis Rats

2015 ◽  
pp. 689-700 ◽  
Author(s):  
E. KOBLIHOVÁ ◽  
O. LUKŠAN ◽  
I. MRÁZOVÁ ◽  
M. RYSKA ◽  
L. ČERVENKA
Keyword(s):  
Survival Rate ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Firefly Luciferase ◽  
Clinical Syndrome ◽  
Hepatocyte Transplantation ◽  
Plasma Albumin ◽  
Lewis Rats ◽  
New Therapeutic Approaches ◽  
Recipient Liver

Acute liver failure (ALF) is a clinical syndrome resulting from widespread damage of hepatocytes, with extremely high mortality rate. Urgent orthotopic liver transplantation was shown to be the most effective therapy for ALF but this treatment option is limited by scarcity of donor organs. Therefore, hepatocyte transplantation (Tx) has emerged as a new therapeutical measure for ALF, however, the first clinical applications proved unsatisfactory. Apparently, extensive preclinical studies are needed. Our aim was to examine if hepatocytes isolated from transgenic “firefly luciferase” Lewis rats into the recipient liver would attenuate the course of thioacetamide (TAA)-induced ALF in Lewis rats. Untreated Lewis rats after TAA administration showed a profound decrease in survival rate; no animal survived 54 h. The rats showed marked increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, in plasma level of bilirubin and ammonia (NH3), and in a significant decrease in plasma albumin. Hepatocyte Tx attenuated the course of TAA-induced ALF Lewis rats which was reflected by improved survival rate and reduced degree of liver injury showing as lowering of elevated plasma ALT, AST, NH3 and bilirubin levels and increasing plasma albumin. In addition, bioluminescence imaging analyses have shown that in the TAA damaged livers the transplanted hepatocyte were fully viable throughout the experiment. In conclusion, the results show that hepatocyte Tx into the liver can attenuate the course of TAA induced ALF in Lewis rats. This information should be considered in attempts to develop new therapeutic approaches to the treatment of ALF.

scholarly journals Antioxidant effects of vitamin E on diclofenac induced hepatotoxicity in male rats

2019 ◽  
Vol 10 (3) ◽  
pp. 1667-1674
Author(s):  
T. Siva ◽  
Girija Sivakumar ◽  
Sankaran PK ◽  
Yuvaraj Maria Francis ◽  
Gayathri T ◽  
...  
Keyword(s):  
Vitamin E ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Diclofenac Sodium ◽  
Clinical Problem ◽  
Male Rats ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Major Clinical Problem

Drug induced liver injury possesses a major clinical problem and has become leading cause of acute liver failure and transplantation. Overstressed liver compromises its detoxification role which may expose it to a variety of diseases and disorders. The present study was to determine whether pre- administration of various doses of vitamin E would have protective effect against diclofenac induced hepatotoxicity in wistar male rats. Twenty-four albino male rats weighing 180-200g were divided equally into four groups. In control group rats were administrated with physiological saline 2ml/kg b.wt /intramuscularly. Another group with 50mg/kg b.wt/ intramuscularly/seven days diclofenac was used for inducing toxicity. In experimental groups rats were administrated with different doses of vitamin E along with diclofenac sodium [200 and 400 IU orally and 50mg/kg b.wt/ intramuscularly/seven days]. Showed that there was a rapid increase in the levels of liver function test in diclofenac treated group, which was significantly decreased after pre-treatment with high dose than low dose of vitamin E. The liver acinus showed Centro acinar necrosis of hepatocytes after 7 days of diclofenac treatment, which was prevented by administration of Vitamin E. Drug-induced liver injury possesses a major clinical problem and has become a leading cause of acute liver failure and transplantation. Overstressed liver compromises its detoxification role which may expose it to a variety of diseases and disorders. Diclofenac sodium is a phenylacetic acid derivative, a widely used nonsteroidal anti-inflammatory drug (NSAID) for the treatment of inflammatory conditions such as osteoarthritis, rheumatoid arthritis, polymyositis, dermatomyositis, dental pain, spondyloarthritis, acute migraine, gout attacks and pain management in gall and renal stones. Although the exact mechanism by with diclofenac injuries liver is not understood, some studies explain the toxicity by affecting cytochrome P 450 leading to the production of active metabolites. Administration of different dose of diclofenac sodium induces severe adverse effects in liver and kidney.

scholarly journals Tc-99m GSA scintigraphy within the first 3 days after admission as an early predictor of outcome in severe acute liver injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuji Suzuki ◽  
Keisuke Kakisaka ◽  
Takuro Sato ◽  
Ryouichi Mikami ◽  
Hiroaki Abe ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Liver Injury ◽  
Area Under The Curve ◽  
Region Of Interest ◽  
Free Survival ◽  
Risk Of Death ◽  
Poor Outcome

AbstractPatients with severe acute liver injury (SLI) usually recover spontaneously. However, some SLI patients progress to acute liver failure with varying degrees of hepatic encephalopathy. Acute liver failure is associated with high mortality and can be substantially reduced by liver transplantation. Therefore, distinguishing SLI patients who might progress to acute liver failure and are at a risk of death is important when evaluating patients needing liver transplantation. The present study aimed to determine whether technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) scintigraphy can predict the prognosis of patients with SLI. This prospective observational study included 69 SLI patients. The accuracy of Tc-99m GSA for predicting death or liver transplantation for 6 months was assessed. Between the two groups of patients stratified based on the cut-off values from the receiver operating characteristic curves, 6-month transplant-free survival was compared. Sixteen (23.2%) patients died or underwent liver transplantation from admission (poor outcome). The hepatic accumulation index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest at 15 min (i.e., LHL15). The LHL15 in the 16 patients (0.686) was significantly lower than that in survivors (0.836; P < 0.0001). The optimal LHL15 cut-off for distinguishing poor outcome and survival was 0.737 with a sensitivity of 81.3%, specificity of 88.7%, and area under the curve of 0.907 (95% CI, 0.832–0.981). When patients were divided into two groups based on the LHL15 cut-off value, the 6-month transplant-free survival was significantly lower in patients with an LHL15 level ≤ 0.737. Tc-99m GSA scintigraphy may help predict the prognosis of patients with SLI.

Hepatoprotective effects of ginsenoside Rk3 in acetaminophen-induced liver injury in mice by activation of autophagy

2021 ◽  
Author(s):  
Linlin Qu ◽  
Rongzhan Fu ◽  
xiaoxuan Ma ◽  
Daidi Fan
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Liver Injury ◽  
Common Causes ◽  
Hepatoprotective Effects

Acetaminophen (APAP)-induced acute liver injury (AIALI) is one of the most common causes of acute liver failure. Owing to the limitations of N-acetylcysteine (NAC), which is the only antidote currently...

Acute Fulminant Hepatic Failure in a Woman Treated With Phenytoin and Trimethoprim-Sulfamethoxazole

2000 ◽  
Vol 124 (12) ◽  
pp. 1800-1803 ◽  
Author(s):  
Marius J-M. Ilario ◽  
Jose E. Ruiz ◽  
Constantine A. Axiotis
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Fulminant Hepatic Failure ◽  
Hepatic Failure ◽  
Acute Hepatic Failure ◽  
Hepatic Necrosis ◽  
Rare Occurrence ◽  
Autopsy Findings ◽  
Massive Hepatic Necrosis

Abstract Massive hepatic necrosis following exposure to phenytoin and trimethoprim-sulfamethoxazole is a rare occurrence and to the best of our knowledge has not been reported previously. Acute hepatic failure following administration of trimethoprim-sulfamethoxazole has rarely been seen, and only 4 cases have been well documented pathologically. We report a case of acute liver failure in a 60-year-old woman following ingestion of phenytoin and trimethoprim-sulfamethoxazole concomitantly over a 9-day period. Autopsy findings revealed acute fulminant hepatic failure. This case demonstrates the effects of chemical-chemical interactions in the potentiation of hepatotoxicity of single agents and specifically illustrates the need for discontinuing trimethoprim-sulfamethoxazole in the presence of early liver injury.

Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines

2001 ◽  
Vol 281 (6) ◽  
pp. G1348-G1356 ◽  
Author(s):  
Amin A. Nanji ◽  
Kalle Jokelainen ◽  
Maryam Fotouhinia ◽  
Amir Rahemtulla ◽  
Peter Thomas ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Liver Injury ◽  
Fish Oil ◽  
Nonheme Iron ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Alcoholic Liver Injury ◽  
Tnf Α ◽  
Cox 2

Alcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-κB (NF-κB) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-κB activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-α and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-κB activation and chemokine production, enhancing liver injury. TNF-α and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.

Liver failure

2020 ◽  
pp. 3089-3100
Author(s):  
Jane Macnaughtan ◽  
Rajiv Jalan
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Hepatic Encephalopathy ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Organ Failure ◽  
Clinical Manifestations ◽  
Chronic Liver ◽  
Chronic Liver Failure

Liver failure occurs when loss of hepatic parenchymal function exceeds the capacity of hepatocytes to regenerate or repair liver injury. Acute liver failure is characterized by jaundice and prolongation of the prothrombin time in the context of recent acute liver injury, with hepatic encephalopathy occurring within 8 weeks of the first onset of liver disease. Acute-on-chronic liver failure is characterized by hepatic and/or extrahepatic organ failure in patients with cirrhosis associated with an identified or unidentified precipitating event. The commonest causes of acute liver failure are acute viral hepatitis and drugs. Acute-on-chronic liver failure is most commonly precipitated by infection, alcohol abuse, and superimposed viral infection. The main clinical manifestations are hepatic encephalopathy, coagulopathy, jaundice, renal dysfunction, and haemodynamic instability. Infection and systemic inflammation contribute to pathogenesis and critically contribute to prognosis. Specific therapy for the underlying liver disease is administered when available, but this is not possible for most causes of liver failure. Treatment is predominantly supportive, with particular emphasis on (1) correction or removal of precipitating factors; (2) if encephalopathy is present, using phosphate enemata, nonhydrolysed disaccharide laxatives, and/or rifaximin; (3) early detection and prompt treatment of complications such as hypoglycaemia, hypokalaemia, cerebral oedema, infection, and bleeding. The onset of organ failure should prompt discussion with a liver transplantation centre. The mortality of acute liver failure (without liver transplantation) is about 40%. Patients with acute liver failure who do not develop encephalopathy can be expected to recover completely. Those who recover from an episode of acute-on-chronic liver failure should be considered for liver transplantation because otherwise their subsequent mortality remains high.

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