scholarly journals Lamivudine-Induced Liver Injury

2015 ◽  
Vol 3 (4) ◽  
pp. 545-550 ◽  
Author(s):  
Lamidi W. B. Olaniyan ◽  
Emmanuel N. Maduagwu ◽  
Olalekan Wasiu Akintunde ◽  
Oladimeji O. Oluwayelu ◽  
Bartholomew I. C. Brai

BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention.AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine.MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10–day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), γ–glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S–transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05.RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses ≥ 100  mg/kg.CONCLUSION: Lamivudine toxicity in rat liver appeared to be mediated by oxidative stress.

Author(s):  
A.A. Adedapo ◽  
O.A. Omoloye ◽  
O.G. Ohore

The toxic effects of an aqueous extract of Abrus precatorius were studied in 20 male white rats over a period of 18 days. The rats were divided into four groups of five rats per group. Those in Group A served as controls while the rats in Groups B, C and D were dosed per os with 400 mg/kg, 800 mg/kg and 1 600 mg/kg of the extract, respectively. Blood samples were collected for haematological and biochemical analysis and specimens of the liver, kidney and testes were taken for histopathological studies. The study showed that the extract of A. precatorius caused decreased levels of packed cell volume, haemoglobin concentration, red blood cell count, white blood cell count, mean corpuscular volume and mean corpuscular haemoglobin. The extract also resulted in increased levels of total serum protein, albumin, alanine amino transaminase, aspartate amino transferase, alkaline phosphatase and total bilirubin. Histologically, testicular degeneration characterized by decreased numbers of lining cells of the epithelium as well as reduction in sperm cells with presence of scattered Sertoli cells were noted. The study thus showed that aqueous extract of Abrus precatorius is toxic and caution should be exercised in its use for medicinal purpose.


1962 ◽  
Vol 203 (1) ◽  
pp. 119-121 ◽  
Author(s):  
Otakar V. Sirek ◽  
Anna Sirek

Total protein-bound hexose, hexosamine, and sialic acid were determined in sera of six littermate mongrel pups at monthly intervals from the 4th day after birth up to the age of 7 months. The concentration of the individual constituents fluctuated considerably from month to month, but the values showed neither a definite trend nor a relationship to weight gain. When the carbohydrate moiety was expressed as percentage of total serum protein concentration, the values were high in newborn pups and diminished after the 1st month of life. This was due to a rise in the concentration of total serum protein, brought about by an increase of the albumin fraction which is low in carbohydrate.


1984 ◽  
Vol 30 (11) ◽  
pp. 1826-1829 ◽  
Author(s):  
W H Porter ◽  
V M Haver ◽  
B A Bush

Abstract Determination of digoxin by fluorescence polarization immunoassay (FPIA) with the Abbott "TDx" is significantly influenced by the concentration of total serum protein. Each 10 g/L increase in serum protein results in an 8% decrease in measured digoxin. Studies with [3H]digoxin confirmed that digoxin binds to the protein pellet during the trichloroacetic acid precipitation step before the immunoassay. Serum protein, or equal concentrations of albumin or gamma-globulin, exert an equivalent effect on the apparent digoxin value. Because the total protein concentration of the assay calibrators is low (50 g/L) compared with its reference interval in serum (60-80 g/L), results by FPIA may be expected to be low by an average of 16% (range, 8-24%). Digoxin results by FPIA will be most nearly accurate when the calibrators include a total protein concentration of about 70 g/L. Patients' specimens with abnormally high or low protein content will give falsely high or low results for digoxin.


2002 ◽  
Vol 22 (2) ◽  
pp. 225-250 ◽  
Author(s):  
C. Allen ◽  
N. Dos Santos ◽  
R. Gallagher ◽  
G.N.C. Chiu ◽  
Y. Shu ◽  
...  

The presence of poly(ethylene glycol) (PEG) at the surface of a liposomal carrier has been clearly shown to extend the circulation lifetime of the vehicle. To this point, the extended circulation lifetime that the polymer affords has been attributed to the reduction or prevention of protein adsorption. However, there is little evidence that the presence of PEG at the surface of a vehicle actually reduces total serum protein binding. In this review we examine all aspects of PEG in order to gain a better understanding of how the polymer fulfills its biological role. The physical and chemical properties of the polymer are explored and compared to properties of other hydrophilic polymers. An evidence based assessment of several in vitro protein binding studies as well as in vivo pharmacokinetics studies involving PEG is included. The ability of PEG to prevent the self-aggregation of liposomes is considered as a possible means by which it extends circulation longevity. Also, a “dysopsonization” phenomenon where PEG actually promotes binding of certain proteins that then mask the vehicle is discussed.


1984 ◽  
Vol 30 (3) ◽  
pp. 446-449 ◽  
Author(s):  
R W Yatscoff ◽  
G J Tevaarwerk ◽  
J C MacDonald

Abstract We have evaluated an affinity-chromatographic procedure for determination of glycated albumin (GA) and glycated total serum protein (GSP). Recovery of these analytes was inversely related to free glucose concentration, thus necessitating removal of free glucose. For this we used molecular-exclusion chromatography on G-25 Sephadex, or dialysis, the latter procedure resulting in significantly (p less than 0.05) lower concentrations of GSP and GA. Total protein concentration and percent glycation are also inversely related, and so protein concentrations must be standardized before the assay. Within- and between-run CVs for both GSP and GA were less than 6.5 and 18%, respectively, the determination of GA being generally the more precise of the two. Labile glycated fractions, lipemia, icterus, hemolysis, and type of anticoagulant did not affect the results, but assay temperature did. Diabetic subjects showed substantially higher concentrations of GA and GSP than did normal subjects. Because of the life span of these analytes in circulation, their measurement may provide a short-term index of glycemic control.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Simone Accarino ◽  
Marco Colucci ◽  
Ettore Pasquinucci ◽  
Giuseppe Sileno ◽  
Vittoria Esposito ◽  
...  

Abstract Background and Aims Generalized edema, non responsive to oral diuretics, is one of the main causes of hospital admission for nephrotic syndrome patients. Although hospital length of stay (LOS) may vary widely, in 2017 the average LOS in acute-care hospitals was lower than 8 days in OECD countries. The aim of the present study was to determine the factors commonly associated with a longer LOS in patients admitted for edema due to nephrotic syndrome in the Nephrology Unit of ICS Maugeri, Pavia, Italy Method In this retrospective study we reviewed the medical records of all patients admitted for nephrotic syndrome between 2012-2020 in the Nephrology Unit of ICS Maugeri. Inclusion criteria were the following: age between 18-85 years of age; severe edema non responsive to oral, low dose diuretics; patients with heart failure, serum creatinine &gt; 3.5 g/dl or on dialysis treatment were excluded from the study. Patients were divided into two groups according to the length of stay: ≤ 7 days or ≥ 8 days. Age, gender, serum protein concentration, creatinine, and hemoglobin; serum cholesterol and tryglicerides, urinary protein excretion rate; types of glomerular disease, weight loss were recorded. Student T tests and one-way Anova were performed to evaluate the differences between the means. Results 60 patients (42 male, 18 female) with a total number of hospital accesses of 93 were enrolled in the study. Mean age was 66.8 ± 13.07 years. Average LOS was 9.02 ± 7.4 days. Protein excretion rate was 6.7 ± 3.6 g/24 hours at the admission and was not statistically changed at discharge. Mean total serum protein and creatinine concentration at the admission were 4.7 ± 0.8 g/dl and 1.8 ± 1.1 mg/dl respectively. Patients with LOS &lt; 7 days were younger (64 ± 11.9 vs 69 ± 13.6 years, p &lt;0.05), had a lower serum creatinine (1.55 ± 0.92 vs 2.08 ± 1.2 mg/dl, p&gt;0.001) and a significantly higher total serum protein concentration (5.02 ± 0.77 vs 4.65 ± 0.76 g/dl, p&lt; 0.001) and haemoglobin (12.6 ± 1.8 vs 11.4 ± 1.8 g/dl, p&lt; 0.05) compared to patients with longer LOS. Proteinuria was not significantly different between the two groups (6.27 ± 3.36 vs 7.1 ± 3.9 g/24 hours, p= NS). While serum cholesterol and tryglicerides were higher in the group of patients with longer LOS, weight loss was similar in the two groups at discharge. Although the difference was not significant, the group with longer hospitalization had a greater number of patients with a diagnosis of focal segmental glomerulosclerosis (FSGS) Conclusion Our results demonstrate that age, total serum protein concentration, serum creatinine, higher lipids and probably the diagnosis of FSGS may affect the hospital length of stay of patients with nephrotic syndrome admitted for severe edema. A more aggressive diuretic treatment may be needed in elderly nephrotic syndrome patients with lower GFR and total serum protein concentration.


PEDIATRICS ◽  
1966 ◽  
Vol 37 (1) ◽  
pp. 51-61
Author(s):  
Jürgen C. Natzschka ◽  
Gerard B. Odell

Infusion experiments were performed in adult rats with two different loads of bilirubin. The maximal biliary excretion was found to be 65± σ 12 µgm bil./100 gm body weight/min. A single intravenous injection of human albumin caused an increase of the serum concentration of bilirubin. The changes in blood hematocrit and total serum protein concentration indicated that the administered albumin remained within the intravascular space for the duration of the experiments. The intravenous administration of PVP was followed by a fall of the serum concentration of bilirubin. This was due to a hemodilution caused by the PVP as indicated by the simultaneous decrease of hematocrit and serum protein concentration. The intravascular bilirubin content remained unchanged after the injection of PVP. The hepatic excretion rate of bilirubin and the bilirubin concentration of the adipose tissue were not significantly altered by the injection of either human albumin or PVP. The results demonstrate that albumin may prevent bilirubin from concentrating in extravascular tissues, and it can also effect a back diffusion of bilirubin already within non-adipose extravascular tissues.


Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 989
Author(s):  
Antonio Cascajosa-Lira ◽  
María Puerto ◽  
Ana I. Prieto ◽  
Silvia Pichardo ◽  
Leticia Díez-Quijada Jiménez ◽  
...  

Propyl-propanethiosulfinate (PTS) is a component of Allium essential oils. This organosulfur molecule can be used as a feed additive to decrease the appearance of bacterial resistances caused by the residues of antibiotics. In previous in vitro genotoxicity studies, contradictory results were reported for PTS. In this work, the in vivo genotoxicity of PTS in male and female rats was assessed for the first time, following OECD (Organisation for Economic Co-operation and Development) guidelines. After oral administration (doses: 5.5, 17.4, and 55.0 mg/kg PTS body weight), a combination of the micronucleus (MN) assay (OECD 474) in bone marrow and the standard and enzyme-modified comet assay (OECD 489) was performed. After necropsy, histopathological studies were also carried out. The results did not show the in vivo genotoxicity of PTS at any doses assayed, revealed by the absence of increased MN, and DNA strand breaks or oxidative DNA damage in the standard and enzyme-modified comet assays. The histopathological study revealed that only the highest dose tested (55.0 mg/kg) in the liver and all dose groups in the stomach presented minimal pathological lesions in the organs studied. Consequently, the present work confirms that PTS is not genotoxic at the doses assayed, and it is a promising natural alternative to synthetic preservatives and antibiotics in animal feed.


2020 ◽  
Author(s):  
Khalid M. Naji ◽  
Bushra Y. Al-Khatib ◽  
Nora Saif Al-Haj ◽  
Myrene R. D’souza

AbstractObjectiveThe present study aimed to investigate the ameliorative effect of melittin, a major polypeptide in the venom of honeybee (Apis mellifera) on isoniazid (INH) and rifampicin (RIF) induced hepatotoxicity in male albino rats. Method: The rats (140-200g) were divided into five groups (n=6): normal control (NC); toxic (T) group treated with INH+RIF (100 mg/kg, p.o.); melittin-treated (Mel15, Mel30) group (15 or 30 µg/kg s.c); and normal recovery (NR) group. Blood and liver samples were collected for biochemical, hematological and histopathological studies respectively.ResultsThe administration of melittin was found to prevent the antitubercular drug-induced alterations in the diagnostic markers; reduced glutathione (GSH), direct bilirubin (DB), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and total serum protein (TSP). Besides, hematological alterations were significantly high (P<0.0001) in Mel-treated groups when compared to the toxic control. The NR group exhibited lower levels of DB, TB, ALP, LDH and TSP. In addition, treatment with melittin offered protection in the NR group with respect to MDA levels.ConclusionEvidence from this study indicate that melittin is beneficial for the prevention of acute hepatic failure in antitubercular drug-induced hepatoxicity.


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