scholarly journals Evaluation of Hepatotoxicity of Aqueous Extract of Valerian (Valeriana Officinalis) in Laboratory Mice

Author(s):  
Zinat Mohammadi ◽  
Leila Pishkar ◽  
Giti Barzin ◽  
Laleh Babaeekhou

Introduction: Concerns have been raised about the toxic effects of medicinal plants due to their increased consumption. Therefore, the aim of the present study was to investigate the hepatotoxic effects of aqueous extract of valerian in laboratory mice. Methods: After preparation of plant materials and aqueous extract of valerian, concentrations of 10 and 20 mg/kg body weight were administered to laboratory mice for 14 days. On the day 14th, blood samples were taken from the hearts of mice after anesthesia and the serum levels of the enzymes alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were studied. Furthermore, the animals' weight was recorded at 0, 7 and 14 days and weight changes were also studied. Results: The results of the present study showed the concentration-dependent effects of aqueous extract of valerian on increasing serum levels of liver enzymes such as ALT, AST, ALP and GGT and the highest serum levels of these enzymes were observed at a concentration of 20 mg/kg. Moreover, the concentration of 20 mg/kg aqueous extract of valerian caused severe weight loss in mice over a period of 14 days. Conclusion: In general, it was concluded that a concentration of 20 mg/kg causes liver damage. However, low concentrations of 10 mg/kg valerian extract showed no toxic effects on the liver. Therefore, in the formulations prepared from valerian, attention to the concentration of the extract is very important and the use of lower concentrations to prevent hepatotoxicity is very important.

Author(s):  
Medhat Mostafa Abozid ◽  
Hoda Ea Farid

 Objective: The current study was designed to estimate the potential protective role of the aqueous extract of rosemary (AER) (Rosmarinus officinalis) against trichloroacetic acid (TCA)-created hepatotoxicity in male albino rats.Methods: Forty male albino rats were separated into four groups of ten: Group I served as control; Group II was given AER (200 mg/kg/day) by gavage; Group III received TCA at the dose 50 mg/kg/day, and Group V was treated with AER (200 mg/kg/day) and received TCA (50 mg/kg/day). The experiment was carried out for 2 months.Results: The toxicity of TCA for rats was revealed by an elevation in liver marker enzymes activities (gamma-glutamyl transferase [GGT], alkaline phosphatase [ALP], aspartate transaminase [AST], alanine aminotransferase [ALT]) and conjugated bilirubin (CB) level, and a decrease in albumin and total protein (TP) levels. The TCA administration also caused a significant increase in the activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), and also malondialdehyde (MDA) level in liver tissues. These biochemical effects were accompanied by histological indicators of liver damage. Treatment with ARE recovered the liver damage instigated by TCA, as showed by perfection of liver enzyme markers (GGT, ALT, AST, ALP), CB, TP and albumin; as well as antioxidant parameters (CAT, SOD, GPx) and lipid peroxidation (MDA) and amelioration of histopathology changes in the liver tissues.Conclusion: It could be concluded that AER supplementation for 2 months in TCA-induced toxicity in rats benefited hepatic antioxidant status and improved liver injury and damage in male albino rats exposed to TCA.


2020 ◽  
Vol 9 (12) ◽  
pp. 3923
Author(s):  
José María Hernández Pérez ◽  
Ignacio Blanco ◽  
Agustín Jesús Sánchez Medina ◽  
Laura Díaz Hernández ◽  
José Antonio Pérez Pérez

Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different genotypes for the alpha-1 antitrypsin (AAT) gene. Methods: Patients (n = 1494) underwent genotyping of the SERPINA1 gene, together with a determination of AAT and GOT and GPT and GGT transaminase levels. Patients with a deficient allele (n = 476) and with a normal genotype were compared. Results: A statistically significant association was found between deficient genotypes and GOT (p < 0.0003), GPT (p < 0.002), and GGT (p < 0.006). Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). In addition, a statistically significant association was found between liver enzymes and AAT values. Conclusion: The PI*Z allele seemed to be a risk factor for the development of liver damage. AAT deficient genotypes were associated with GOT, GPT, and GGT altered values. Low AAT levels were associated with high GPT and GGT levels.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Danielle Cristiane Baldo ◽  
Alessandra Dellavance ◽  
Maria Lucia Gomes Ferraz ◽  
Luis Eduardo C. Andrade

Abstract Background Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years. Methods 327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50–7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (ɣGT) and ELF score were measured by automated methods. Results Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.45% and 8.86% per year; respectively), anti-PDC-E2 avidity (3.02% and 4.94%/year) and ELF score (3.24% and 2.71%/year). IIF-AMA and ɣGT increased in BN/AMA+ (6.59% and 2.36%) and decreased in PBC (− 4.89%/year and − 3.88%/year). In BN/AMA+ individuals there was positive correlation of ELF with IIF-AMA titer (r = 0.465; p < 0.001) and with anti-PDC-E2 levels (r = 0.239; p < 0.001). Expansion of autoantibody targets along time occurred in 39% BN/AMA+ and 49% PBC patients. The frequency of BN/AMA+ with high probability of having established PBC increased from 7 to 14%. Conclusions BN/AMA+ individuals present an orchestrated increase in ELF score and humoral autoimmune response over time, indicating an opportunity for early therapeutic intervention and prevention in autoimmunity.


2018 ◽  
Vol 29 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Olorunfemi R. Molehin ◽  
Anne A. Adeyanju ◽  
Stephen A. Adefegha ◽  
Oluwasanmi O. Aina ◽  
Blessing A. Afolabi ◽  
...  

AbstractBackground:Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5′-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4).Methods:CCl4(0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats.Results:CCl4significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05).Conclusions:The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.


2009 ◽  
Vol 407 (1-2) ◽  
pp. 67-71 ◽  
Author(s):  
Francisco Gude ◽  
Jesús Rey-Garcia ◽  
Carmen Fernandez-Merino ◽  
Luis Meijide ◽  
Luis García-Ortiz ◽  
...  

2019 ◽  
Vol 8 (2) ◽  
pp. 41-45
Author(s):  
Elias Adikwu ◽  
Ebinyo Clemente Nelson

The concurrent use of tramadol and diclofenac may increase hepatotoxic risk due to their individual hepatotoxic effects. This study assessed the hepatotoxic effect of tramadol-diclofenac administration in albino rats. Twenty-four adult male albino rats (200-220g) randomized into four groups were orally administered with tramadol (12mg/kg/day), diclofenac (6mg/kg/day) and tramadol-diclofenac for 14 days respectively. The rats were anesthetized, blood samples were collected and evaluated for serum liver function and lipid parameters. Liver samples were weighed and evaluated for biochemical parameters and histology. The effects of tramadol-diclofenac on the body and liver weights did not differ significantly (p>0.05) when compared to control. Also, effects were not significant (p>0.05) on blood glucose, and serum cholesterol, triglyceride, low and high density lipoprotein cholesterol levels when compared to control. Liver and serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, gamma–glutamyl transferase, conjugated bilirubin and total bilirubin increased significantly in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Furthermore, significant decreases in liver catalase, glutathione, superoxide dismutase, glutathione peroxidase levels with significant increases in malondialdehyde levels occurred in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Hepatocyte necrosis was observed in rats treated with tramadol-diclofenac. Tramadol-diclofenac may increase hepatotoxic risk at doses used for this study.


2009 ◽  
Vol 28 (9) ◽  
pp. 591-598 ◽  
Author(s):  
MT Yakubu ◽  
BB Bukoye ◽  
AT Oladiji ◽  
MA Akanji

Aqueous extract of Bambusa vulgaris L. leaves at 250 and 500 mg/kg body weight was investigated for toxic effects in pregnant rabbits. Apparently healthy, female rabbits (Dutch) weighing between 1.62 and 1.70 kg as previously used in our abortifacient study were paired overnight with male rabbits in ratio 2:1 and those that became pregnant were completely randomized into three groups (A-C). Group A (the control), received orally 1.85 mL/kg body weight (3 mL) of distilled water thrice daily on days 1-9 of pregnancy while groups B and C were treated orally with the same volume corresponding to 250 and 500 mg/kg body weight of the extract. Clinical signs of toxicity were not observed in all the animals during the study. The extract did not significantly alter (p > .05) the serum follicle stimulating hormone and total protein content of the pregnant rabbits throughout the exposure period whereas, the concentrations of luteinizing hormone, progesterone, albumin, globulin, urea and calcium decreased in the serum of the rabbits. At 250 mg/kg body weight, the extract increased kidney alkaline phosphatase (ALP) activity whereas at 500 mg/kg body weight of the extract, the ALP level was similar to the control group. Liver ALP at all doses, as well as the activity of gamma glutamyl transferase (GGT) at 500 mg/kg body weight was reduced. This reduction was accompanied by an increase in serum ALP and GGT at these doses. At 250 mg/kg, the extract increased kidney GGT. Conversely, at 500 mg/ kg, kidney GGT activity decreased. Liver and serum GGT were not altered by the 250 mg/kg. The extract also increased the serum levels of creatinine, uric acid, sodium, potassium and bicarbonate ions as well as total and conjugated bilirubin. In the hepatocytes of extract-treated animals, there was no evidence of necrosis, inflammation, fibrosis and degenerative changes in the central vein and radiating hepatic cords, while the glomerulus and the tubules of the nephrons also remained intact. The alterations in biochemical parameters by the aqueous extract of B. vulgaris leaves suggests adverse effect on the synthetic, secretory, reabsorptive and excretory functions of liver and kidney of the animals. Therefore, the absence of histopathological lesions in the hepatocytes and nephrons implies that histopathological changes are not a sensitive assay for the assessment of tissue damage by the extract.


2018 ◽  
Vol 46 (1) ◽  
pp. 8
Author(s):  
Neylisa Dario Lazaro ◽  
Flavia Barbieri Bacha ◽  
Rayane Chitolina Pupin ◽  
Juliana Paniago Lordello de Paula ◽  
Paula Velozo Leal ◽  
...  

Background: Stryphnodendron fissuratum is a tree from the Brazilian Cerrado. Its fruit is toxic to cattle and can cause clinical digestive signs, hepatogenous photosensitization, and abortion. Cases of poisoning in cattle, goats and guinea pigs have been experimentally reproduced; however, photosensitization could not be reproduced. The aim of this work was to describe an outbreak of natural poisoning and experimental reproduction in cattle, both with hepatogenous photosensitization.Materials, Methods & Results: Its described and natural outbreak and an experimental poisoning. In the outbreak, three bovines in the acute phase and three in the chronic phase were examined. Blood samples were collected from all of these animals in order to measure serum levels of aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), urea, and creatinine. The first three animals underwent necropsy and histopathological evaluation. The experiment was conducted with two nine-month-old calves that received an oral paste made with crushed S. fissuratum fruits mixed with water. These fruits were collected at a farm at which cattle poisoning cases had occurred. Blood samples were collected in order to measure serum levels of AST, GGT, urea, and creatinine, before plant administration and then daily during the experimental period. Skin biopsies were taken before plant administration and new one after the first signs of skin lesions. The natural outbreak affected 52 of 160 bovine (31 calves and 21 cows) in the lot. Two calves and 14 cows died. Clinical signs consisted of depression, ataxia, incoordination, behavioral changes, decubitus, and death. One animal that died and 36 others that recovered had photodermatitis. Necropsy findings in the animals consisted of bad corporal condition, pale kidneys, evidence of liver lobular pattern, dry rumen contents, and full bladder. In two animals, fruit seeds were found in the rumen, and one animal had ulcers and transmural edema in the abomasum. Microscopically, mild to moderate renal tubular distension, accumulation of proteinaceous material in lumen with mild to moderate swelling, and epithelial necrosis. In the liver, swelling of hepatocytes and moderate bile stasis was detected. Enzymes values in all evaluated bovines were higher than those considered normal for the species. Experimentally, both calves became ill and one died. The clinical signs were apathy, inappetence, wobbling, weight loss, and goosebumps. One of them had jaundice, tearing, photophobia, ear skin detachment, and ulcers at the muzzle, nostrils and ventral face of the tongue. This animal was euthanized in extremis, and the necropsy findings showed generalized jaundice, evidence of increased liver lobular pattern, thick bile, pale kidneys, and esophageal, tongue, and epiglottal ulcers. Microscopically, the lesions were similar to those described during the natural outbreak. The skin biopsy from the calf that recovered showed perivascular edema and mild eosinophilia.Discussion: The diagnosis was made based on clinical signs, necropsy findings, histopathological lesions, and epidemiological analysis. Experimentally, the plant was toxic at the administered doses. Photosensitization was the most common clinical sign during the natural outbreak and until now, has never been experimentally reproduced. Based on histopathological lesions observed in this study, we can consider that is from hepatogenous origin. The results showed that the kidney lesions have an important role during the pathogenesis caused by this poisoning and during disease evolution.


2020 ◽  
Vol 77 (7) ◽  
pp. 680-687
Author(s):  
Sanja Vukadinovic-Stojanovic ◽  
Zlatan Stojanovic

Background/Aim. Patients suffered from chronic alcoholic disease very often have depression and cardiomyopathy. Treatment with several antidepressants is associated with prolonged QT interval, ventricular arrhythmias and sudden death. The aim of this study was to investigate the relation between the severity of depression, serum levels of gamma-glutamyl transferase (GGT), as a marker of liver damage, and the possible influence of paroxetine use on duration of QT interval in patient who started treatment of chronic alcoholic dependence. Methods. The study included 147 male patients (older than 18 years of age) suffering from alcohol addiction, who were also diagnosed with depressive disorder on the basis of DSM-IV criterion and positive Hamilton Rating Scale for Depression (HRSD) at the beginning of hospitalization. Out of total number of patients, 49 were randomly selected to be treated with antidepressant paroxetine at a dose of 20 mg once daily during 20 days. The global QTc interval was automatically determined. Results. By applying the generalised linear model, the statistically significant positive correlation between the length of QTc interval and serum values of GGT, that is, intensity of alcoholism (p = 0.002) and values of the HRSD score, that is, intensity of depression (p = 0.021) was established in the sample of 147 depressed alcoholic patients before the application of paroxetine. In spite of the vulnerability of patients due to the heart damage and the liver dysfunction arising from alcohol consumption, as well as altered patients' drugs metabolism, no elongation of QTc interval resulting from the application of paroxetine was established. The length of QTc interval 20 days after paroxetine administration was 401.43 ms and before paroxetine administration it was 403.31 ms. The difference in QTc interval length (after and before paroxetine administration) was ?QTc = - 1.88 ms (p = 0.524). Conclusion. The results indicated that the severity of depression and GGT serum levels positively correlated with the length of QT interval. On the other hand, paroxetine after 20 days of usage did not prolong QT interval.


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