scholarly journals The Role of the Immune System in Nevirapine-Induced Subclinical Liver Injury of a Rat Model

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Zanelle Bekker ◽  
Andrew Walubo ◽  
Jan B. du Plessis

In this study, the role of the immune system in nevirapine- (NVP-) induced subclinical liver injury was investigated by observing for changes of some immune parameters during the initial stages of NVP-induced hepatotoxicity in a rat model. In the acute phase, two test-groups of 10 Sprague-Dawley rats each were administered with bacterial lipopolysaccharide (LPS) or saline (S) intraperitoneally, followed by oral NVP, after which 5 rats from each group were sacrificed at 6 and 24 hours. For the chronic phase, two groups of 15 rats each received daily NVP, and on days 7, 14, and 21, five rats from each group were administered with either LPS or S, followed by that day’s NVP dose, and were sacrificed 24 hours later. NVP caused liver injury up to seven days and progressively increased IL-2 and IFN-γ levels and lymphocyte count over the 21 days. NVP-induced liver injury was characterized by apoptosis and degeneration changes, while, for LPS, it was cell swelling, leukostasis, and portal inflammation. Coadministration of NVP and LPS attenuated NVP-induced liver injury. In conclusion, the immune system is involved in NVP toxicity, and the LPS effects may lay the clue to development of therapeutic strategies against NVP-induced hepatotoxicity.

2017 ◽  
Vol 15 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Mirza Kalam Urfi ◽  
Md. Mujahid ◽  
Md. Akhlaquer Rahman ◽  
Md. Azizur Rahman

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Soon Yew Tang ◽  
Irwin Kee M. Cheah ◽  
Pei Ern Ng ◽  
Aina Hoi ◽  
Andrew M. Jenner

Studies have identified that serum-free hemoglobin subunits correlate positively with the severity of nonalcoholic fatty liver disease (NAFLD). However, the role of hemoglobin in the development of NAFLD remains unclear. In the present study, a rat model of NAFLD was developed, using a westernized diet high in saturated fat and refined sugar. Since a “westernized” diet is also high in red meat, we tested the effect of hemoglobin as a dietary source of heme in our model. Sprague-Dawley rats were fed ad libitum for 4 weeks either control diet (7% fat), westernized diet (WD, 18% fat + 1% cholesterol), hemoglobin diet (7% fat + 2.5% Hb), or westernized and hemoglobin diet (18% fat + 1% cholesterol + 2.5% Hb). Rats fed WD developed features of NAFLD, including insulin resistance and accumulation of liver fatty acids in the form of triglycerides, increased lipid peroxidation (F2-Isoprostanes), and liver fibrotic marker (hydroxyproline). Hemoglobin consumption significantly influenced several biomarkers of NAFLD and hepatic biochemistry, suggesting a possible interaction with diet and/or liver lipid pathways. The complex mechanisms of interaction between WD and hemoglobin in our rat model warrants further studies to examine the role of dietary heme on NAFLD.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Virginia Fernández ◽  
Romina Vargas ◽  
Valentina Castillo ◽  
Nicolás Cádiz ◽  
Daniela Bastías ◽  
...  

The role of iron (Fe)-induced prooxidant status in Fe preconditioning against ischemia (1 h)-reperfusion (20 h) induced liver injury was assessed using N-acetylcysteine (NAC) (1 g/kg) before Fe (50 mg/kg), given to male Sprague Dawley rats on alternate days during 10 days. IR significantly increased serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, with drastic changes in liver histology, hepatic glutathione depletion, and nuclear factor-κB (NF-κB) p65 diminution (P<0.05) (ELISA). Fe-induced liver oxidative stress, as evidenced by higher protein carbonyl/glutathione content ratios (P<0.05) at days 11 and 12 after treatment, was abolished by NAC. Under these conditions, short-term Fe administration exerted significant protection against IR liver injury, as shown by 85% and 60% decreases in IR-induced serum AST and ALT (P<0.05), respectively, and normalization of hepatic histology, glutathione levels, and NF-κB activation, changes that were suppressed by NAC administration prior to Fe. Results of this study indicate that NAC administration prior to an iron protocol reestablishes IR liver injury, supporting the role of Fe-induced transient oxidative stress in hepatoprotection and its potential clinical application.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lu Yin ◽  
Shen Zhao ◽  
JoongBum Moon ◽  
Peng Sun ◽  
Jiangang Wang ◽  
...  

Introduction: Post-resuscitation myocardial dysfunction has been recognized as one of the major causes of fatal outcomes after initial successful cardiopulmonary resuscitation (CPR). Previous research demonstrated that Netrin-1 improved post ischemic injury cardiac function via preservation of mitochondrial integrity. In the present study, we investigated the role of netrin-1 after cardiac arrest. Hypothesis: We hypothesized that the netrin-1 alleviated post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Methods: A total of sixteen male Sprague-Dawley rats (450-550 g) were randomized to two groups as follows: (1) Control group (C group); (2) Netrin-1 group (N group). Ventricular fibrillation was induced and untreated for 8 mins followed by 8 mins of CPR. Netrin-1 or saline were given at the onset of precordial compression. Ejection fraction (EF) was measured by echocardiography at baseline, 1,2,3 and 4 hours after ROSC. Results: Eight rats were resuscitated in the netrin-1 group and 7 rats were resuscitated in the saline group. In both groups, EF decreased after resuscitation when compared to the baseline (#p < 0.05). In the netrin-1 group, EF decreased from ( 68.1±3.4)% at baseline to (51.1±5.0)% at 1 hour post-resuscitation. In the saline group, EF decreased from (67.7±2.1)% at baseline to (44.5±5.3)% at 1 hr post-resuscitation. EF was better in the netrin-1 group than in the saline group at 2, 3 and 4 hours post-resuscitation (*p < 0.05) ( Figure 1). Conclusion: Netrin-1 alleviates post-resuscitation myocardial dysfunction in a rat model of cardiac arrest.


2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.


1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.


2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.


2006 ◽  
Vol 74 (7) ◽  
pp. 4387-4389 ◽  
Author(s):  
Rachel Marion ◽  
Asiya Baishanbo ◽  
Gilles Gargala ◽  
Arnaud François ◽  
Philippe Ducrotté ◽  
...  

ABSTRACT In 5-day-old immunocompetent Sprague-Dawley rats infected with either 102 or 105 Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.


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