Hepatoprotective effects of hydroethanolic extracts of Crocus sativus tepals, stigmas and leaves on carbon tetrachloride induced acute liver injury in rats

Introduction: The present study investigated the hepatoprotective effects of stigmas, tepals and leaves of Crocus sativus on carbon tetrachloride (CCL4) induced liver injury in rats. Methods: Hydroethanolic extracts of Crocus sativus (stigmas, tepals and leaves) were administrated daily for 14 days by oral gavage. In the present study, 30 male rats divided into five groups were treated as 1: normal rats gavaged with distilled water; 2: intoxicated rats gavaged with distilled water and injected with CCL4; 3: rats treated with stigmas extract and injected with CCL4; 4: rats treated with tepal extract and injected with CCL4; 5: rats treated with leaf extract and injected with CCL4. Bodyweight and the relative liver weight were determined. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total cholesterol, triglycerides, bilirubin direct and total, total protein, albumin, urea and creatinine measured in plasma. Malondialdehyde (MDA) was quantified in liver homogenate. Results: The experimental data showed that the stigmas and tepals extracts significantly prevented weight body loss and improved the relative liver weight. They significantly protected against elevation of ALT, AST, direct bilirubin, total bilirubin, LDH, ALP, creatinine and MDA. Also, they enhanced significantly total proteins and albumin compared to the CCL4 control group. Moreover, leaves reduced ALT, AST, total bilirubin, LDH and MDA significantly. Conclusion: In conclusion, these results suggest that tepals, stigmas, and leaves extracts of Crocus sativus have hepatoprotective effects on CCL4 induced liver injury in rats.

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Explore the mechanism of Swertia mussotii Franch. for hepatoprotective effects with iTRAQ-LC-MS/MS

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666201020111301 ◽

2020 ◽

Vol 23 ◽

Author(s):

Haixia Yun ◽

Xinyu Wu ◽

Yiwei Ding ◽

Wendou Xiong ◽

Xianglan Duan ◽

...

Keyword(s):

Lipid Metabolism ◽

Carbon Tetrachloride ◽

Liver Injury ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Total Bilirubin ◽

Acute Liver Injury ◽

Proteome Analysis ◽

Ppi Networks ◽

Hepatoprotective Effects

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.

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The Natural Antioxidants Curcumin and Silymarin Afforded Hepatoprotective Effects against Deferasirox-Induced Hepatotoxicity

10.21203/rs.3.rs-990751/v1 ◽

2021 ◽

Author(s):

Enass Y. Osman ◽

Souzan E. Abo-Elnasr ◽

Shaimaa Mohammed Zaher ◽

Norhan Ahmed AbuoHashish

Keyword(s):

Total Bilirubin ◽

Curcuma Longa ◽

Natural Antioxidants ◽

Group Iv ◽

Control Group ◽

Distilled Water ◽

Oral Gavage ◽

Once Daily ◽

Group Iii ◽

Hepatoprotective Effects

Abstract Deferasirox belongs to a new is a bishydroxyphenyltriazoles iron chelator used for treatment of chronic iron overload. The use of Deferasirox is associated with hepatotoxicity. Silymarin is a benzo gamma-pyrones flavonoid which affords hepatoprotection and preserves hepatocyte membranes by its antioxidant effect. Curcumin is a poly-phenol compound naturally concentrated in the herb Curcuma longa. The present study was conducted to evaluate and compare the hepatoprotective effects of both silymarin and curcumin against deferasirox-induced hepatotoxicity in rats and to explore the potential mechanisms account for their hepatoprotective effects. The present study was carried out using 32 male wistar randomly assigned into 4 groups (8 rats each) as follows; Group1: served as normal control group in which rats received distilled water (0.5ml per rat) by oral gavage. Group II (Deferasirox group) in which hepatotoxicity was induced by oral administration of deferasirox in a dose of 100 mg/kg once daily for 4 weeks dissolved in distilled water for a concentration of 35mg/ml. Group III (deferasirox+ curcumin) in which rats received curcumin in a dose of 100 mg/kg daily dose by oral gavage for 4 weeks suspended in distilled water for a concentration of 35 mg/ml one hour before administration of deferasirox. Group IV (deferasirox+ silymarin) in which rats received silymarin in dose of 7.56 mg/kg once daily by oral gavage for 4 weeks suspended in distilled water for a concentration of 2.7mg/ml one hour before administration of deferasirox. At the end of the treatment period, all rats were sacrificed by cervical dislocation, blood samples were collected for measurement of ALT, AST, ALP and total bilirubin. Liver samples were used for measurement of MDA, GSH and IL-6. Histopathological and immunohistochemistry were also done. The present data revealed that rats pretreated with curcumin or silymarin exhibited significant reduction in ALT, AST, ALP, total bilirubin, IL-6 and MDA levels with significant elevation of GSH level compared to deferasirox group. In-between group comparison revealed that there was a more significant reduction in ALT, AST, ALP, total bilirubin, IL-6 and MDA in group IV compared to group III. In conclusion, both curcumin and silymarin represent natural protective agents against Deferasirox-induced hepatotoxicity due to their antioxidant and anti-inflammatory effects.

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The effect of Liv-52 on liver ischemia reperfusion damage in rats

BMC Pharmacology and Toxicology ◽

10.1186/s40360-019-0380-0 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Orhan Cimen ◽

Hüseyin Eken ◽

Ferda Keskin Cimen ◽

Arif Burak Cekic ◽

Nezahat Kurt ◽

...

Keyword(s):

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Sham Operation ◽

Distilled Water ◽

Liver Ischemia ◽

Group Level ◽

Healthy Group ◽

Hepatoprotective Effects ◽

Wistar Male Rats

Abstract Background Liver ischemia reperfusion (I/R) damage which is frequently seen in clinical hepatobiliary surgeries has no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by the Ministry of Health of India. The aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats. Methods Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n = 6) 1 h prior to I/R application and distilled water was given orally to IR (n = 6) and HG (n = 6) groups as a solvent. Ischemia was determined as 1 h, and reperfusion was identified as 6 h in animals. Results Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage in liver tissue has been improved histopathologically. Conclusions Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.

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Anti-Inflammatory and Hepatoprotective Effects of Ganoderma lucidum Polysaccharides against Carbon Tetrachloride-Induced Liver Injury in Kunming Mice

Pharmacology ◽

10.1159/000493896 ◽

2019 ◽

Vol 103 (3-4) ◽

pp. 143-150 ◽

Cited By ~ 8

Author(s):

Yu-Sheng Chen ◽

Quan-Zhan Chen ◽

Zhen-Jiong Wang ◽

Chun Hua

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Liver Tissue ◽

Ganoderma Lucidum ◽

Acute Liver Injury ◽

Liver Weight ◽

Inflammatory Factors ◽

Ganoderma Lucidum Polysaccharides ◽

Hepatoprotective Effects ◽

Anti Inflammatory

Background: Ganoderma lucidum Polysaccharides (GLPS) were found to possess various pharmacological properties including anti-inflammatory and hepatoprotective activities. However, the effect and possible mechanism of GLPS treatment on liver injury have not yet been reported. Therefore, this study aimed to explore the potential anti-inflammatory and hepatoprotective effects and possible mechanism of GLPS in carbon tetrachloride (CCl4)-induced acute liver injury mice. Summary: GLPS significantly reduced the activation of NLRP3 inflammasome and improved liver function in liver injury mice. It significantly inhibited CCl4-induced changes of alanine aminotransferase and aspartate aminotransferase activities in serum, as well as nitric oxide synthase (NOS) and cytochrome P450 2E1 (CYP2E1) activities in liver tissue; it also remarkably decreased levels of liver weight and index, total bilirubin, interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α in serum, as well as malondialdehyde and IL-1β in liver tissue. Protein expression levels of liver NLRP3, ASC, and Caspase-1 were also downregulated, while the glutathione level in liver tissue was remarkably enhanced in GLPS groups compared to that of the model group. Key Message: These results suggested that GLPS may be a potential for the prevention and treatment of acute liver injury with liver inflammation. The possible mechanism may be related to the inhibition of free radical lipid peroxidation, NOS, and CYP2E1 activities and activation of liver inflammatory factors.

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The effect of Liv-52 on liver ischemia reperfusion damage in rats

10.21203/rs.2.14473/v4 ◽

2019 ◽

Author(s):

Orhan Cimen ◽

Huseyin Eken ◽

Ferda Keskin Cİmen ◽

Arif Burak Cekic ◽

Nezahat Kurt ◽

...

Keyword(s):

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Sham Operation ◽

Distilled Water ◽

Liver Ischemia ◽

Group Level ◽

Healthy Group ◽

Hepatoprotective Effects ◽

Wistar Male Rats

Abstract Background: Liver ischemia reperfusion (I/R) damage which is frequently seen in clinical hepatobiliary surgeries has no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by the Ministry of Health of India. The aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats. Methods: Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n=6) one hour prior to I/R application and distilled water was given orally to IR (n=6) and HG (n=6) groups as a solvent. Ischemia was determined as one hour, and reperfusion was identified as six hours in animals. Results: Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage in liver tissue has been improved histopathologically. Conclusions: Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.

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The effect of Liv-52 on liver ischemia reperfusion damage in rats

10.21203/rs.2.14473/v1 ◽

2019 ◽

Author(s):

Orhan Cimen ◽

Huseyin Eken ◽

Ferda Keskin Cİmen ◽

Arif Burak Cekic ◽

Nezahat Kurt ◽

...

Keyword(s):

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Sham Operation ◽

Distilled Water ◽

Liver Ischemia ◽

Group Level ◽

Healthy Group ◽

Hepatoprotective Effects ◽

Wistar Male Rats

Abstract Background: Liver ischemia reperfusion (I/R) damage is frequently seen in clinical hepatobiliary surgeries and there is no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by Ministry of Health of India. Therefore, the aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats.Methods: Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n-6) one hour prior to I/R application and distilled water was given orally to IR (n-6) and HG (n-6) groups as a solvent. In animals, ischemia was determined as one hour, and reperfusion was identified as six hours.Results: Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage occurred in liver tissue has been improved histopathologically.Conclusions: Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.

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The effect of Liv-52 on liver ischemia reperfusion damage in rats

10.21203/rs.2.14473/v2 ◽

2019 ◽

Author(s):

Orhan Cimen ◽

Huseyin Eken ◽

Ferda Keskin Cİmen ◽

Arif Burak Cekic ◽

Nezahat Kurt ◽

...

Keyword(s):

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Sham Operation ◽

Distilled Water ◽

Liver Ischemia ◽

Group Level ◽

Healthy Group ◽

Hepatoprotective Effects ◽

Wistar Male Rats

Abstract Background: Liver ischemia reperfusion (I/R) damage is frequently seen in clinical hepatobiliary surgeries and there is no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by Ministry of Health of India. Therefore, the aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats. Methods: Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n-6) one hour prior to I/R application and distilled water was given orally to IR (n-6) and HG (n-6) groups as a solvent. In animals, ischemia was determined as one hour, and reperfusion was identified as six hours. Results: Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage occurred in liver tissue has been improved histopathologically. Conclusions: Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.

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The effect of Liv-52 on liver ischemia reperfusion damage in rats

10.21203/rs.2.14473/v3 ◽

2019 ◽

Author(s):

Orhan Cimen ◽

Huseyin Eken ◽

Ferda Keskin Cİmen ◽

Arif Burak Cekic ◽

Nezahat Kurt ◽

...

Keyword(s):

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Sham Operation ◽

Distilled Water ◽

Liver Ischemia ◽

Group Level ◽

Healthy Group ◽

Hepatoprotective Effects ◽

Wistar Male Rats

Abstract Background: Liver ischemia reperfusion (I/R) damage which is frequently seen in clinical hepatobiliary surgeries has no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by the Ministry of Health of India. The aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats. Methods: Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n-6) one hour prior to I/R application and distilled water was given orally to IR (n-6) and HG (n-6) groups as a solvent. Ischemia was determined as one hour, and reperfusion was identified as six hours in animals. Results: Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage in liver tissue has been improved histopathologically. Conclusions: Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.

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EFFECTS OF PARTIALLY HYDROGENATED PYRIDINES (CYANOTHIOACETAMIDE DERIVATIVES) ON THE BLOOD OF RATS WITH COMBINED PARACETAMOL-ALCOHOLIC LIVER INJURY

Kuban Scientific Medical Bulletin ◽

10.25207/1608-6228-2019-26-2-106-114 ◽

2019 ◽

Vol 26 (2) ◽

pp. 106-114 ◽

Cited By ~ 1

Author(s):

Elena Yu. Bibik ◽

Bogdan S. Krivokolysko ◽

Anna A. Burdeynaya ◽

Andrey V. Demenko ◽

Konstantin A. Frolov ◽

...

Keyword(s):

Liver Injury ◽

Bilirubin Level ◽

Total Bilirubin ◽

Total Bilirubin Level ◽

Male Rats ◽

Control Group ◽

Alcoholic Liver Injury ◽

Reference Drug ◽

Tert Butyl ◽

Pharmacological Correction

Aim. In this research, we studied the parameters of blood biochemical analysis in rats with combined paracetamol-alcoholic liver injury after its pharmacological correction by newly synthesized partially hydrogenated pyridines (cyanothioacetamide derivatives).Materials and methods. 50 samples of new derivatives of partially hydrogenated pyridines synthesized on the basis of the “Chemex” Research Laboratory of the Vladimir Dal’ Lugansk National University underwent virtual bioscreening, which allowed the selection of 4 compounds, the biological activity of which may be associated with the effect on the protein synthesis and detoxifi cation function of the liver. The experiment was conducted on 48 white outbred male rats. For 14 days, the rats of the control and experimental groups were intragastrically injected with 1 ml of 40% ethanol and paracetamol at a dose of 500 mg/kg once a day. Pharmacocorrection with a thiotriazoline reference drug (50 mg/kg) and pyridine derivatives at a dose of 5 mg/kg was performed from the fourth day. On the 15th day, blood was sampled to determine the level of total bilirubin, alanine aminotransferase, aspartate aminotransferase and thymol turbidity test.Results. The value of total bilirubin in the blood of the rats treated with CV046 compounds was 34.88% lower than that in the control group. The animals of the test groups receiving CV047 also showed signifi cant differences with the control group in terms of bilirubin level (a decrease of 31.78%). The AST values in the blood of rats in the test groups had no signifi cant differences as compared with intact animals. Following 10 days of pharmacological correction of combined paracetamol-alcoholic liver injury with CV146, the total bilirubin level in the blood decreased by 26.36% in comparison with the control group, with the activity of ALT and AST demonstrating the levels of intact values.Conclusions. The conducted screening studies of four partially hydrogenated pyridines — cyanothioacetamide derivatives — using the model of combined paracetamol-alcoholic liver injury when used at a dose of 5 mg/kg during ten days have shown a high hepatoprotective and detoxifying activity of the following three compounds: СV046 (2-[(9-tert-butyl-1,5-dicyano4-oxo-3-azaspiro[5,5]undec-1-en-2-yl)thio]-N-(2-ethylphenyl)acetamide — IUPAC), СV047 (2-[(9-tert-butyl-1,5-dicyano-4-oxo-3-azaspiro[5,5]undec-1-en-2-yl)thio]-N-(4-fl uorophenyl) acetamide) and СV146 (benzyl 4-(4-chlorophenyl)-5-cyano-6-({2-[(3,4-dimethylphenyl)amino]-2-oxoethyl}thio)-2-methyl-1,4-dihydropyridine-3-carboxylate).

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