In vivo Toxicity Assessment after the Detoxification of Aflatoxin Compounds – Contaminated Wheat and Corn by Ozone Gas

Aflatoxins (AFs) are dangerous mycotoxins, which include a great number of lipophilic molecules produced by aerobic microscopic fungi belonging to the genus Aspergillus causes health hazard including death to human and livestock. The objective of this study was to evaluate the effectiveness of ozone gas treatment on the fungal growth and detoxification of AFs - contaminated wheat and corn grains. Ozone concentration treatments 40 mg / Kg wheat for 1 hour and 80 mg / Kg corn for 2 hours of exposure time respectively were applied to contaminated samples of wheat and corn grains. It was observed that completely inhibition of Aspergillus growth and consequently the total aflatoxin content was decreased. In vivo, the biosafety assessment for 72 male albino rats fed on diet containing 70% wt. of ozone treated AFs – contaminated grains were evaluated comparing to control groups. Results indicated that rats fed on AFs contaminated grains have significantly increased the serum enzymes activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), malondialdehyde (MDA) content as well as the serum levels of creatinine, urea, glucose, total cholesterol (TC) and triglycerides (TG). Also, it was observed that a significant decrease in the level of serum total protein (TP), albumin (Alb), reduced glutathione (GSH) and testosterone hormone comparing to control groups. However, the oral administration of ozonized groups ameliorated the biochemical parameters compared to rats fed on contaminated grains. Moreover, histopathological studies of liver, kidney and testis tissues of rats fed on contaminated grains that revealed different lesions and changes in tissues, inversely to that improving effects in tissues of ozonized contaminated grains – fed rats. It was concluded that ozonization treatment were most effective in reduction of mold count and degradation of aflatoxins content for grains during storage.

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Hepatotoxic Assessment of Tramadol-Diclofenac Use: A Study in a Rat Model

Biology Medicine & Natural Product Chemistry ◽

10.14421/biomedich.2019.82.41-45 ◽

2019 ◽

Vol 8 (2) ◽

pp. 41-45

Author(s):

Elias Adikwu ◽

Ebinyo Clemente Nelson

Keyword(s):

Density Lipoprotein ◽

Serum Levels ◽

The Body ◽

Albino Rats ◽

Gamma Glutamyl Transferase ◽

Cholesterol Levels ◽

Concurrent Use ◽

Hepatotoxic Effect ◽

Hepatocyte Necrosis ◽

Glutamyl Transferase

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.

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Hepatoprotective and Reno-protective Effects of Artichoke Leaf Extract and Rosemary Extract against Paracetamol Induced Toxicity in Albino Rats

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2020/v32i3230935 ◽

2020 ◽

pp. 67-81

Author(s):

Eman Aly Sadeek Fadlalla ◽

Sahar Mousa Galal

Keyword(s):

Leaf Extract ◽

Serum Levels ◽

Negative Control ◽

Rosemary Extract ◽

Albino Rats ◽

Gamma Glutamyl Transferase ◽

Protective Effects ◽

Liver And Kidney ◽

Glutamyl Transferase ◽

Artichoke Leaf Extract

Background: Paracetamol overdose is a predominant cause of hepatotoxicity and nephrotoxicity in both humans and experimental animals. There is an emerging focus on plant products to find a highly effective and reliable drug for the prevention of paracetamol –induced toxicity. Objective: In this study, we investigated the Hepatoprotective and Reno-protective Effects of artichoke (Cynara scolymus L.) Leaf extract and rosemary (Rosmarinus officinalis L.) extract against paracetamol Induced toxicity in Albino Rats. Materials and Methods: Rats were divided into five groups: Negative control, paracetamol (1000 mg/kg dose) PCT, artichoke leaf extract “ALE” (1.5 g/kg, orally + paracetamol for 30 d), rosemary extract “RE” (125 mg/kg + paracetamol for 30 days) and the last group was treated with PCT+ ALE+ RE for 30 days. Results: Paracetamol caused marked liver damage as noted by significant increased activities of serum aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase. Paracetamol also raised serum levels of urea, creatinine, and Cystatin-C. In addition, there was a significant decrease in serum total protein and albumin. Paracetamol caused an elevation in lipid peroxidation paralleled with significant decline in reduced glutathione (GSH) level and activities of glutathione-S- transferase (GST), glutathione (GPX) peroxidase, and superoxide dismutase (SOD) in the liver and kidney. These results are confirmed in the histological examination of the liver and kidney. Conclusion: Treatment with artichoke leaf extract (ALE) and rosemary extract (RE) produced a potential protection of the liver and kidney against biochemical and histological alterations and oxidative stress induced by paracetamol.

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Effect of nanopolysaccharide (BSEPS) from Bacillus subtilis sp. on thioacetamide-induced liver fibrosis in rats

Bulletin of the National Research Centre ◽

10.1186/s42269-019-0244-1 ◽

2019 ◽

Vol 43 (1) ◽

Author(s):

Manal G. Mahmoud ◽

Mohsen S. Asker ◽

Mohamed E. El Awady ◽

Amal I. Hassan ◽

Nadia A. R. Zaharan ◽

...

Keyword(s):

Bacillus Subtilis ◽

Liver Fibrosis ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Periodate Oxidation ◽

Hepatic Tissue ◽

Albino Rats ◽

Gamma Glutamyl Transferase ◽

Glutamyl Transferase ◽

Tgf Β1

Abstract Background Nanomedicine contributes to the efficiency of pharmacological treatments and progresses rapidly. The present study was designed to produce exopolysaccharide (BSEPS) from Bacillus subtilis sp. strain reported in our previous study was further characterized, and its BSEPS for synthesis of the nanoparticle Ag-BSEPS using microwave heating to determine the possible effects of a prepared solution containing Ag-BSEPS versus thioacetamide (TAA) evoked liver fibrosis in Wister albino rats. Nanoparticles with silver (Ag) core have been synthesized in an aqueous solution after exposure of BSEPS to periodate oxidation. Animals were split into four groups: I - control rats, water ad libitum for 6 weeks; II - rats were injected with TAA 200 mg/kg-1 3 times/week for 4 weeks IP; III - Ag-BSEPS 100 mg/kg-1 IP twice a week for 6 weeks; and IV - TAA, as group II followed by Ag-BSEPS as group III. The antifibrotic effects of Ag-BSEPS were appraised by determining different hepatotoxicity indices, oxidative stress, and inflammatory and liver fibrosis markers. Results Nanoparticles were obtained with a diameter size range of 50–100 nm characterized by SEM and TEM without using any harmful reagents. Results evinced considerably reduced activity of liver functions such as transaminases (AST, ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in the group which received TAA followed by Ag-BSEPS compared to the other group which received only TAA. In the current results, the administration of Ag-BSEPS showed an improvement in the proinflammatory cytokines. On the contrary, the antioxidant enzymes in liver homogenates revealed significant improvement (concentration of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT) increases) in animals with TAA-induced liver damage followed by Ag-BSEPS. Moreover, the activities of the fibrotic markers transforming growth factor-beta 1(TGF-β1) and type III pro-collagen (PCIII) were increased in liver tissues in the group which was given TAA alone as compared to the controls. The percentage of fibrosis of hepatic tissue had a positive correlation with the levels of PCIII and TGF-β1, followed by Ag-BSEPS compared to the TAA group without nanocomposite treatment. Microscopic examinations revealed inhibitory effects of Ag-BSEPS on inflammatory changes and deterrent of liver fibrosis. Conclusion It was suggested that the biochemical and histological amelioration observed in Ag-BSEPS (100 mg/kg-1 twice a week for 6 weeks) treated the fibrotic rats.

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Antidiabetic and antiulcerative potential of Garcinia lanceifolia Roxb. bark

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00101-6 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Nilutpal Sharma Bora ◽

Partha Sarathi Bairy ◽

Abdus Salam ◽

Bibhuti Bhusan Kakoti

Keyword(s):

Body Weight ◽

Serum Levels ◽

Northeast India ◽

Scientific Data ◽

Antidiabetic Activity ◽

Histological Evaluation ◽

Albino Rats ◽

Antiulcer Activity ◽

Dose Dependent

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.

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Flavonoids content of 70% methanolic extract of Erucaria pinnata (Viv.) and its effect as anticancer and antiangiognic: in vitro, in vivo and docking study

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1779 ◽

2020 ◽

Vol 11 (1) ◽

pp. 25-38

Author(s):

Nadia I. Zakhary ◽

Emad E.H. El Gemeie ◽

Adel K. Youssef ◽

Marwa Abdel-salam Ibrahim Metwaly

Keyword(s):

Cytotoxic Activity ◽

Methanolic Extract ◽

Coastal Region ◽

Experimental Period ◽

Docking Study ◽

Gamma Glutamyl Transferase ◽

Histopathological Studies ◽

Glutamyl Transferase

Erucaria pinnata (Viv.) is a wild annual plant growing in North-Western Coastal Region in Egypt. This study reports for the first time the cytotoxic activity of different extracts of Erucaria pinnata plant against HEP-G2 cell line. The 70% methanolic extract (E1) recorded the best potent cytotoxic activity (IC50=13.6 µg/ml), so we analysis the flavonoids constituent of this extract using HPLC, which show that our extract is rich with important flavonoids compounds (rutin, quercetin, leutolin, etc.). We evaluated its antitumor activity against hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) (200mg/Kg. b.wt., i.p, single dose) after two weeks, animals received carbontetrachloride (CCl4) (3ml/Kg. b.wt., SC, once a week for 6 weeks) and the experiment continued for 44 weeks in rats. After the experimental period, the administration of DEN/CCl4 showed significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, gamma-glutamyl transferase (γGT) and significant decrease in the levels of total proteins and albumin content in the serum with reduction in the liver antioxidants, including superoxide dismutase (SOD) and catalase (CAT). This was accompanied by increases in serum specific tumor markers (AFP). The 70% methanolic plant extract (E1) was orally administrated (400mg/kg/day respectively) for the whole study period, and it showed a significant improvement at the different biological liver functions, remodeled the antioxidant enzymes activity and down-regulated the serum AFP. All these findings were confirmed by histopathological studies of the liver samples obtained from all groups. In addition, we evaluated its antiangeogenic activity by docking study against VEGFR-2 tyrosine kinase after it showed an ability to inhibit the VEGFR-2 expression in vitro and inhibit the concentration of VEGF-A in vivo. The hepatoprotective effect of our extract was attributed to its antioxidant and antiangeogenic activity.

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PROTECTIVE ROLE AND ANTIOXIDANT ACTIVITY OF AQUEOUS EXTRACT OF ROSMARINUS OFFICINALIS AGAINST TRICHLOROACETATE-INDUCED TOXICITY IN LIVER OF MALE RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i6.25353 ◽

2018 ◽

Vol 11 (6) ◽

pp. 420

Author(s):

Medhat Mostafa Abozid ◽

Hoda Ea Farid

Keyword(s):

Aqueous Extract ◽

Liver Damage ◽

Protective Role ◽

Rosmarinus Officinalis ◽

Male Rats ◽

Control Group ◽

Albino Rats ◽

Gamma Glutamyl Transferase ◽

Group I ◽

Glutamyl Transferase

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.

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Serum Levels of Glutamate-Pyruvate Transaminase, Glutamate-Oxaloacetate Transaminase and Gamma-Glutamyl Transferase in 1494 Patients with Various Genotypes for the Alpha-1 Antitrypsin Gene

Journal of Clinical Medicine ◽

10.3390/jcm9123923 ◽

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

Keyword(s):

Liver Damage ◽

Serum Levels ◽

Gamma Glutamyl Transferase ◽

Glutamate Oxaloacetate Transaminase ◽

Glutamate Pyruvate Transaminase ◽

Gamma Glutamyl ◽

Glutamate Pyruvate ◽

Alpha 1 Antitrypsin ◽

Glutamyl Transferase ◽

Normal Genotype

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.

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Evolving liver inflammation in biochemically normal individuals with anti-mitochondria antibodies

Autoimmunity Highlights ◽

10.1186/s13317-019-0120-x ◽

2019 ◽

Vol 10 (1) ◽

Author(s):

Danielle Cristiane Baldo ◽

Alessandra Dellavance ◽

Maria Lucia Gomes Ferraz ◽

Luis Eduardo C. Andrade

Keyword(s):

Liver Fibrosis ◽

Rat Kidney ◽

Surrogate Marker ◽

Serum Levels ◽

Autoimmune Response ◽

Primary Biliary Cholangitis ◽

Gamma Glutamyl Transferase ◽

Normal Individuals ◽

Glutamyl Transferase

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.

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Sildenafil, a phosphodiesterase-5 inhibitor, offers protection against carbon tetrachloride-induced hepatotoxicity in rat

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0011 ◽

2018 ◽

Vol 29 (1) ◽

pp. 29-35 ◽

Cited By ~ 4

Author(s):

Olorunfemi R. Molehin ◽

Anne A. Adeyanju ◽

Stephen A. Adefegha ◽

Oluwasanmi O. Aina ◽

Blessing A. Afolabi ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Density Lipoprotein ◽

Serum Levels ◽

Selective Inhibition ◽

Guanosine Monophosphate ◽

Control Group ◽

Gamma Glutamyl Transferase ◽

Protective Agent ◽

Glutamyl Transferase ◽

Phosphodiesterase 5

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.

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