scholarly journals HEPATOPROTECTIVE EFFECTS OF L-CITRULLINE AGAINST DOXORUBICIN-INDUCED LIVER DAMAGE IN RATS: AN ANALYSIS OF SERUM BIOMARKERS

Author(s):  
KELVIN THEANDRO GOTAMA ◽  
VIVIAN SOETIKNO ◽  
MELVA LOUISA ◽  
WAWAIMULI AROZAL

Objective: The antineoplastic agent doxorubicin (DOX) is known for causing liver toxicity. Its metabolism in hepatocytes causes oxidative stress, which,in turn, induces DNA damage, lipid peroxidation, ATP depletion, and apoptosis. L-citrulline (CIT), a commonly found agent in fruits like watermelon,has piqued interest due to its antioxidant properties. In the body, CIT is converted to nitric oxide, which has been shown to mitigate hepatic injuryby scavenging free radicals, improving hepatic sinusoidal microcirculation, and inhibiting neutrophilic infiltration. This study aims to investigate CITability to prevent DOX-induced hepatotoxicity.Methods: A total of 20 Wistar rats were randomized to receive either DOX (10 mg/kg BW) or NaCl 0.9%. DOX-intoxicated group was further randomizedto either received low-dose CIT (300 mg/kg BW), high-dose CIT (600 mg/kg BW), or aquadest. CIT was given orally for 6 days and DOX throughintraperitoneal injection on days 4 and 5. Serum was obtained and hepatotoxicity was assessed with serum levels of aspartate aminotransferase(AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Statistical analysis was done with one-way ANOVA and Tukey’s test.Results: Serum ALT, AST, and GGT were increased significantly compared to that of normal group. CIT administration in both the doses could decreasethe serum levels of ALT and AST significantly compared to that of DOX group. In this study, CIT in both the doses could reduce the serum levels of GGTcompared to that of DOX group though not statistically significant.Conclusions: This study suggests that CIT exerts hepatoprotective effect, as evident by the attenuation of serum biomarkers.

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.


2018 ◽  
Vol 16 (1) ◽  
pp. 133-140 ◽  
Author(s):  
Riaz Ullah ◽  
Mansour S. Alsaid ◽  
Abdelaaty A. Shahat ◽  
Almoqbil Abdulaziz Naser ◽  
Abdullah A. Al-Mishari ◽  
...  

AbstractThe detoxification, metabolism, and excretion of various endogenous and exogenous materials occur mainly in the liver. Liver diseases are a global concern, and classified as chronic hepatitis, cirrhosis, and hepatosis. The development of safe hepatoprotective agents remains an unmet need. Therefore, we investigated the antioxidant effects of methanolic and n-hexane fractions of Zilla spinosa (ZSM and ZSH, respectively) and Hammada elegans (HEM and HEH, respectively) against carbon tetrachloride (CCl4)-induced liver toxicity in rats. Antioxidant activity was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The rats were divided into 11 groups (n=6)–group, 1 (control), group 2 (CCl4 only), group 3 (CCl4+silymarin 10 mg/kg), group 4 (CCl4+HEM 250 mg/kg), group 5 (CC14+HEM 500 mg/kg), group 6 (CCl4+HEH 250 mg/kg), group, 7 (CCl4+HEH 500 mg/kg), group, 8 (CCl4+ZSM 250 mg/kg), group 9 (CCl4+ZSM 500 mg/kg), group 10 (CCl4+ZSH 250 mg/kg), and group 11 (CCl4+ZSH 500 mg/kg). Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, and total bilirubin were measured. The extent of hepatic injury was histopathologically assessed. Treatment with ZSM and ZSH at 250 and 500 mg/kg did not significantly affect biochemical results compared with the CCl4 only group. However, treatment with both HEM and HEH at 250 and 500 mg/kg provided significant (p<0.001) results compared with the CCl4 only group. These results were consistent with histological findings. HEM and HEH at 250 μg/mL significantly inhibited DPPH radical formation by 38.E6 and 35.65%, rerpectively. However antioxidant effects of ZSM and ZSH were insignificant.


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.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Tarfa Albrahim ◽  
Manal Abdulaziz Binobead

It is common for food to be made more palatable through the use of the flavour enhancer monosodium glutamate, also known as vetsin powder. The purpose of the study described in this paper was to explore how vetsin-induced hepatic toxicity, DNA fragmentation, damage, and oxidative stress modifications could be mitigated with moringa leaf extract (MLE). To that end, 40 male rats were separated into four groups: normal control, positive control or MLE, vetsin, and vetsin combined with MLE. Results indicated that, compared to the control group, the levels of serum alanine aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), liver malondialdehyde (MDA), DNA damage, injury, PCNA, and P53 expressions were significantly enhanced by the administration of vetsin (P<0.05). However, the vetsin group had significantly reduced levels of albumin, globulin, total protein, liver glutathione (GSH), superoxide dismutase enzyme (SOD), catalase, and glutathione S-transferase (GST) enzyme activities (P<0.05) by comparison to control. Meanwhile, modifications in liver functions, oxidative stress, DNA damage, liver injury, and PCNA expression were alleviated when vetsin was administered alongside MLE. The authors conclude that vetsin may have many side effects and that MLE can ameliorate biochemical changes, oxidative stress, hepatic injury, PCNA, and P53 alterations induced by vetsin administration.


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.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Atef M. Al-Attar ◽  
Isam M. Abu Zeid

The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors.


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 ◽  
...  

2021 ◽  
Vol 42 (6) ◽  
pp. 3305-3320
Author(s):  
Camila Moura de Lima ◽  
◽  
Gustavo Antônio Boff ◽  
Sergiane Baes Pereira ◽  
Alexsander Ferraz ◽  
...  

Excess body fat can cause a series of metabolic and mechanical effects on the body. Therefore, this study aimed to verify the clinical, metabolic, and risk factors of overweight (OW) cats. For the acceptance of participation in the research, the tutors were asked to answer a questionnaire containing 34 questions and to point out the body condition score (BCS) on a sheet containing nine images of different scores (1 to 9 on a 9-point scale). Thereafter, the body evaluations were performed as a classification of the BCS on a scale from 1 to 9, with an ideal score (IS) of BCS 5 and OW for BCS > 5. Further, the lean mass index and morphometric measurements (thoracic and abdominal circumferences and height and length of the patella to calcaneal tuberosity) were performed to estimate the percentage of body fat. Systolic blood pressure was measured using the non-invasive Doppler method and blood was collected for hemogram and serum biochemistry (creatinine, urea, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, glucose, triglycerides, and cholesterol). After these analyses, we sought to guide and raise the awareness of the tutors to promote the correct nutritional and environmental management of the animals. Thirty adult cats were divided into two groups, based on the classification of the BCS, with eight having an IS and 22 being OW. The OW group was found to have a low level of physical activity, hypercholesterolemia, and higher values of body characteristics. Additionally, there was a median agreement between the perceptions of the clinician and the tutors. Therefore, it was concluded that the main laboratory alteration found in the obese cats was hypercholesterolemia, which was a critical parameter. It was observed that a low degree of physical activity could cause excess weight gain. It was found that the guardians of the cats with ideal weight underestimated the BCS, which could contribute to the supply of excess food and consequently, obesity. Thus, this study was sought to guide and raise the awareness of tutors, to promote the correct nutritional and environmental management thereby providing welfare and quality of life to the animals.


2021 ◽  
Vol 9 (3) ◽  
pp. 130-134
Author(s):  
M. I. Sakhatsky ◽  
Yu. V. Osadcha

In the conditions of industrial poultry farming, the body of hens is constantly exposed to numerous technological stressors, the least studied of which are long-term ones, that can provoke chronic stress. One such technological stressor is an increase in the level of cage equipment, which is used by producers to obtain a larger amount of products from 1 m2 of poultry area. The aim of this work was to study the physiological state of the hen’s body based on the clinical biochemical analysis of their blood serum, depending on the battery cages height. In the conditions of a modern complex for the production of edible eggs in a poultry house with an area of 2 915 m2, 4 groups of hens were formed, each of them was kept on a separate floor-analogue in terms of area and cage equipment. Each floor was equipped with «Big Dutchman» 3-tier battery cages. Battery cages of each floor were separated from each other by a lattice floor so that cages of 1–3 tiers entered up to the 1st floor, 4–6 tiers – up to the 2nd, 7–9 tiers – up to the 3rd, and 10–12 tiers – up to 4th floor of cage equipment. Biochemical parameters and activity of hens blood serum enzymes were determined on a BioChem FC-360 biochemical analyzer. For this, 30 blood samples with a volume of 1.0–1.5 ml were taken from axillary veins of laying hens in each group at the age of 18 weeks (at the beginning of the study) and at 52 weeks. It was found that increasing the layering of cage equipment does not have a negative impact on the hen’s body. So, for keeping hens in cages of multi-tier battery cages located on floors 2–4 (4–12 tiers), the biochemical status and activity of their blood serum enzymes were within the physiological norm. Whereas, for hens kept in battery cages of the a multi-tiered system on the 1st floor there was an increase in glucose levels of 60.5–71.0%, creatinine – by 9.7–12.3%, phosphorus – 82.6–100.0%, was observed a decrease in calcium to phosphorus ratio 46.7–50.0%, which was confirmed by an increase in the activity of alkaline phosphatase by 22.3–27.0%, as well as an increase in the activity of aspartate aminotransferase by 3.2–13.8%, lactate dehydrogenase - by 48.5–65.1% and gamma-glutamyl transferase – by 16.4–20.6%. It has been proven that the main consequences of chronic stress caused by keeping hens in the lower floor cells of the multi-tiered battery cage are reflected in the biochemical parameters of their serum, namely increased glucose, creatinine, enzyme activity and violation of calcium to phosphorus ratio.


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