scholarly journals Resveratrol Protects Against Methotrexate-Induced Hepatic Injury in Rats

2010 ◽  
Vol 13 (2) ◽  
pp. 303 ◽  
Author(s):  
Tugba Tunalı-Akbay ◽  
Ozer Sehirli ◽  
Feriha Ercan ◽  
Goksel Sener

Purpose. The aim of this study to investigate the possible protective effect of resveratrol on some liver and serum/plasma parameters in methotrexate induced toxicity in rats. Methotrexate is used widely to treat various neoplastic diseases such as acute lymphoblastic leukemia, lymphoma, solid cancers, and autoimmune diseases. We hypothesized that resveratrol has a potential to decrease the oxidant damage in MTX-induced hepatic injury. Methods. Following a single dose of methotrexate (20 mg/kg, i.p.), either saline or resveratrol (10 mg/kg, orally) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the liver was removed to measure malondialdehyde and glutathione levels, myeloperoxidase and thromboplastic activities and collagen content. Aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase activity were measured in the serum samples, while TNF-α and total antioxidant capacity were assayed in plasma samples. Results. Our results showed that MTX administration increased the hepatic malondialdehyde levels, myeloperoxidase and thromboplastic activities and collagen contents and decreased glutathione, while these alterations were reversed in resveratrol-treated group. Elevated aspartate aminotransferase and alanine aminotransferase activities and TNF-α level observed following MTX treatment was depressed with resveratrol. Conclusions. The present study showed that resveratrol protects against methotrexate-induced hepatic injury and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.

2019 ◽  
Vol 18 (4) ◽  
pp. 297-302
Author(s):  
Sriset Yollada ◽  
Chatuphonprasert Waranya ◽  
Jarukamjorn Kanokwan

Bergenin is a C-glucoside derivative of gallic acid but its antioxidant and hepatoprotective effects have not previously been compared with gallic acid. Male ICR mice were administered bergenin (10, 50, and 250 mg/kg/day) or gallic acid (100 mg/kg/day) for 7 consecutive days before a single administration of ethanol (5 g/kg). Liver sections were histopathologically examined. Aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels were determined in plasma. Total glutathione, reduced glutathione, and oxidized glutathione levels were determined in liver homogenates. Ethanol induced hepatic injury with prominent histopathological markers including nuclear pyknosis and necrotic areas and this accorded with increases in the plasma levels of aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde. Moreover, ethanol disturbed hepatic glutathione homeostasis by reducing glutathione stores. Hepatic injury in the ethanol-induced mice was prevented with bergenin and gallic acid by significant decreases in plasma aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels and restoration of the hepatic glutathione profile through an increase in the reduced glutathione/oxidized glutathione ratio. Bergenin at 10 mg/kg/day showed comparable hepatoprotective activity to gallic acid in an ethanol-induced mouse model of oxidative stress. Therefore, bergenin might be a promising candidate for further development as a novel hepatoprotective product.


Author(s):  
B. P. Kale ◽  
Mujawar Jahir Rauf

Background: Paracetamol is a recognized antipyretic, analgesic drug which produces hepatic necrosis in high doses. Eclipta alba elaborates a vast array of biologically active compounds that are chemically diverse and structurally complex.Methods: Randomized open controlled experimental study Estimated levels of Serum aspartate aminotransferase (AST), Serum alanine aminotransferase (ALT) and Hepatoprotective action of in High doses of Paracetamol on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity.Results: ALT in all the groups including Control group (A) was (51.8±4.56IU/L). Paracetamol treated group (B) the ALT level increased at 48 hours and continued to be high up to 60 days (136.4±20.73IU/L) then decreased to (113.7±11.35IU/L) at 90 days. AST in all the groups including Control group (A) was (22.5±1.23IU/L). Appropriate antioxidant in appropriate doses as a matter of routine whenever hepatotoxic or potentially hepatotoxic drugs are prescribed. In Paracetamol treated group (B) the AST level increased at 48 hours and continued to be high up to 60 days (99.4±9.73IU/L) then decreased to (85.4±7.39IU/L) at 90 days.Conclusions: Appropriate antioxidant in appropriate doses as a matter of routine whenever hepatotoxic or potentially hepatotoxic drugs are prescribed.


Author(s):  
Alsaady Malath Azeez

Background: Liver is major organ of metabolism, which required to be protected from drugs and their metabolites harmful effect by using substances like vitamins and herbs. Objective: To evaluate vit. D3 protective effect in paracetamol induced hepatotoxicity of male rabbits. Material and method:18 male local rabbits divided to three groups. First group receive paracetamol in three spaced doses for 24 hours to induce acute hepatoxicity while the second group receive vit.D3 as single intramuscular injection 24 hours prior induction of acute hepatoxicity and third group was control without treatment. After 24 hours from paracetamol, induce acute hepatotoxicity blood samples collected to measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin. Results: There were significant elevation (p≤0.05) in serum liver enzymes of treatment groups in relation to control and non-significant decrease in alanine aminotransferase (ALT), aspartate aminotransferase (AST) of vit.D3 treated group. Conclusion: As conclusion, a model of acute paracetamol induced hepatotoxicity successfully established with no mortality. Although, non-significant vit.D3 possess protective effect in relation to liver function test.


2017 ◽  
Vol 21 (1) ◽  
pp. 30-33 ◽  
Author(s):  
Devika Tayal ◽  
Mrinal Gupta ◽  
Binita Goswami

ABSTRACT Background Sample storage for prolonged periods can lead to alterations in routine biochemical parameters. Aim This study was undertaken to observe the biochemical changes on serum samples when they are stored for prolonged periods at –20°C on different routine biochemical parameters. Results Significant changes were observed in serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and potassium levels after 72 hours of storage, which further deteriorate in 3 months. Rest of the parameters did not show any significant alteration. Conclusion Prolonged storage of samples lead to alterations in the analyte concentration in serum. Serum glucose, AST, ALT, creatinine, and potassium levels should be estimated within 72 hours if prolonged storage is unavoidable. In conclusion, all the parameters should be assayed within 24 hours to avoid misinterpretation of results and better patient care. How to cite this article Tayal D, Gupta M, Goswami B. Does Prolonged Storage of Serum Samples alter the Lab Results? Indian J Med Biochem 2017;21(1):30-33.


2020 ◽  
Vol 13 (11) ◽  
pp. 2326-2329
Author(s):  
Zahraa Mustafa Al-Jumaa ◽  
Eva Aisser Ajaj ◽  
Mohammad Osamah Dahl

Aim: The current study was conducted to explore evidence of hepatitis B virus (HBV) infection in dogs in Nineveh Province, Iraq. Materials and Methods: Serum samples of 78 dogs were used to (i) estimate levels of the antibodies against HBV through enzyme-linked immunosorbent assay and (ii) measure the activity of liver function enzymes. Results: Seropositive dogs for HBV constituted 9% of total tested dogs. The differences in seropositivity among males compared to females and among different ages were not statistically significant. Liver function enzymes analysis revealed a significant increase in the activity of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in seropositive dogs compared to those seronegative. Conclusion: Hepatitis B is evident in dogs in Nineveh Province, Iraq, with a significant impact on liver function in affected dogs. It is important to confirm this evidence through molecular tests.


Author(s):  
Haixia Yun ◽  
Xinyu Wu ◽  
Yiwei Ding ◽  
Wendou Xiong ◽  
Xianglan Duan ◽  
...  

Background and Objective : A Tibetan traditional herb named Swertia mussotii Franch., also called “Zangyinchen” by the local people of Qinghai-Tibet area, has been used to protect the liver from injury for many years. However, the curative effect and molecular mechanism of the herb have not been demonstrated clearly. Materials and Methods: In our study, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin levels were examined after S. mussotii Franch. treatment in the acute liver injury of the carbon tetrachloride-induced rat model. Then, Proteome Analysis was applied to explore the potential mechanism of SMT for hepatoprotective effects after iTRAQLC-MS/MS analysis (isobaric tag for relative and absolute quantification-liquid chromatograph-mass spectrometer with tandem mass spectrometry). Results: Serum results showed, alanine aminotransferase, aspartate aminotransferase, total bilirubin levels of rats with acute liver injury were all improved with SMT treatment. Moreover, Proteome Analysis suggested that, with S. Mussotii Franch. treatment, the levels of lipid catabolic process and lipid homeostasis were all enhanced. And the results of protein-protein interaction (PPI) analysis illustrated that these proteins assembled in PPI networks were found almost significantly enriched in response to lipid, negative regulation of lipase activity, response to lipopolysaccharide etc. Furthermore, the downregulated MRP14 and MRP8 proteins were found involved in the lipid metabolism, which may indicate the mechanism of SMT protection liver from ALI induced by carbon tetrachloride. Conclusion: SMT herb could play a role in hepatoprotection and alleviate the effect of acute liver injury by impacting the lipid metabolism associated biological process.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hirotaka Ochiai ◽  
Takako Shirasawa ◽  
Takahiko Yoshimoto ◽  
Satsue Nagahama ◽  
Akihiro Watanabe ◽  
...  

Abstract Background Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to ALT ratio (AST/ALT ratio) have been shown to be related to non-alcoholic fatty liver disease or insulin resistance, which was associated with chronic kidney disease (CKD). However, it is unclear whether ALT and AST/ALT ratio are associated with CKD. In this study, we examined the relationship of ALT and AST/ALT ratio to CKD among middle-aged females in Japan. Methods The present study included 29,133 women aged 40 to 64 years who had an annual health checkup in Japan during April 2013 to March 2014. Venous blood samples were collected to measure ALT, AST, gamma-glutamyltransferase (GGT), and creatinine levels. In accordance with previous studies, ALT > 40 U/L and GGT > 50 U/L were determined as elevated, AST/ALT ratio < 1 was regarded as low, and CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or proteinuria. Logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for CKD. Results “Elevated ALT and elevated GGT” and “elevated ALT and non-elevated GGT” significantly increased the OR for CKD when compared with “non-elevated ALT and non-elevated GGT” (OR: 2.56, 95% CI: 2.10–3.12 and OR: 2.24, 95% CI: 1.81–2.77). Compared with “AST/ALT ratio ≥ 1 and non-elevated GGT”, “AST/ALT ratio < 1 and elevated GGT” and “AST/ALT ratio < 1 and non-elevated GGT” significantly increased the OR for CKD (OR: 2.73, 95% CI: 2.36–3.15 and OR: 1.68, 95% CI: 1.52–1.87). These findings still remained after adjustment for confounders. Conclusions Elevated ALT was associated with CKD regardless of GGT elevation. Moreover, low AST/ALT ratio was also associated with CKD independent of GGT elevation.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 117-117
Author(s):  
Nicole C Burdick Sanchez ◽  
Jeffery A Carroll ◽  
Paul R Broadway ◽  
Tom S Edrington ◽  
Ilkyu Yoon ◽  
...  

Abstract This study was conducted to determine if feeding calves NaturSafe would reduce the acute phase response (APR) to lipopolysaccharide (LPS) challenge. Crossbred steers (n=32; 274±2 kg) were randomly allotted to two treatment diets: 1) Control, fed a standard receiving ration, and 2) NaturSafe, fed the Control ration supplemented with NaturSafe at 12 g/hd/d (NaturSafe®, Diamond V). On d22, steers were fitted with indwelling jugular catheters and rectal temperature monitoring devices and placed in individual stalls. On d23, steers were challenged i.v. with 0.25 µg/kg BW LPS. Serum samples were collected and sickness behavior scores (SBS) recorded at 0.5-h intervals from -2 to 8h and at 24h relative to LPS challenge. Rectal temperatures were greater (P=0.01) in NaturSafe compared to Control steers for the following time intervals following LPS challenge: 6 to 11h, 13h, 15 to 20h, and 22 to 24h. Additionally, SBS were reduced (P&lt; 0.01) in NaturSafe compared to Control steers. White blood cell concentrations were greater (P=0.05) in NaturSafe compared to Control steers prior to the LPS challenge, yet the response to LPS did not differ between treatments (P &gt;0.05). A treatment × time interaction for serum cortisol concentrations (P&lt; 0.01) showed an increase at 0.5 and 2h post-challenge but a reduction at 3h in NaturSafe compared to Control steers. Additionally, fibrinogen was greater (P&lt; 0.01) in NaturSafe compared to Control steers. There was a treatment × time interaction (P&lt; 0.01) for TNF-α where concentrations were reduced from 1 to 2h post-challenge in NaturSafe compared to Control steers. Serum IL-6 tended (P=0.09) to show a reduction in serum concentrations in NaturSafe compared to Control steers. There was a tendency (P=0.07) for a treatment × time interaction for IFN-γ. Overall these data suggest a priming effect of NaturSafe on the innate immune system of steers, resulting in an attenuated APR to the LPS challenge.


Author(s):  
Afsar Ali Mian ◽  
Isabella Haberbosch ◽  
Hazem Khamaisie ◽  
Abed Agbarya ◽  
Larissa Pietsch ◽  
...  

AbstractResistance remains the major clinical challenge for the therapy of Philadelphia chromosome–positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common “gatekeeper” mutation T315I. Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia. By inhibiting the BCR-ABL1 kinase, crizotinib efficiently suppressed growth of Ph+ cells without affecting growth of Ph− cells. It was also active in Ph+ patient-derived long-term cultures (PD-LTCs) independently of the responsiveness/resistance to other TKIs. The efficacy of crizotinib was confirmed in vivo in syngeneic mouse models of BCR-ABL1- or BCR-ABL1T315I-driven chronic myeloid leukemia–like disease and in BCR-ABL1-driven acute lymphoblastic leukemia (ALL). Although crizotinib binds to the ATP-binding site, it also allosterically affected the myristol binding pocket, the binding site of GNF2 and asciminib (former ABL001). Therefore, crizotinib has a seemingly unique double mechanism of action, on the ATP-binding site and on the myristoylation binding pocket. These findings strongly suggest the clinical evaluation of crizotinib for the treatment of advanced and therapy-resistant Ph+ leukemia.


2021 ◽  
Vol 22 (12) ◽  
pp. 6428
Author(s):  
Hanon Lee ◽  
Dong Hun Lee ◽  
Jang-Hee Oh ◽  
Jin Ho Chung

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.


Sign in / Sign up

Export Citation Format

Share Document