The Protective Effect of Silymarin on LipopolysaccharideInduced Liver Toxicity in Male Wistar Rat

Author(s):  
Fahimeh Nourbakhsh ◽  
Samaneh Borooni ◽  
Elaheh Tajbakhsh

Background and Aims: Lipopolysaccharide (LPS) triggers production of reactive oxygen species and inflammatory cytokines. Nowadays Silybum marianum has been shown to treat liver and gall bladder disorders, especially to protect the liver against poisoning from various toxins. Therefore, we decided to evaluate the protective effect of silymarin on LPS-induced liver toxicity in male Wistar rat. Materials and Methods: Totally, 40 male Wistar rats were divided into 4 groups (n=10 in each): The animals were treated with silymarin for two weeks before the biochemical tests. Apoptosis was assessed by evaluating the amount of proteins in liver tissues by western blotting. Results: LPS induced hepatotoxicity as evidenced by histopathological damages and biochemical abnormalities. Data showed that malondialdehyde level significantly increases in the liver of LPS-treated rats. Destructive effects of LPS on histopathological and biochemical parameters were improved. LPS also increased expression of Bax/Bcl2 ratio and activation of caspase 3, caspase 8 and caspase 9. Western blot analysis showed silymarin treatment inhibiting apoptosis stimulated by LPS in the liver (p<0.001). Conclusions: The results of this research demonstrated that silymarin can exert protective effects against toxic effects of LPS in rat liver. Antiinflammatory drug can play a protective role in attenuating the liver inflammation induced by LPS injection.

2019 ◽  
Vol 10 (4) ◽  
pp. 2755-2764
Author(s):  
Sumathi Rajamani ◽  
Gobinath Kalyanasundaram ◽  
Tamizharasi Sengodan ◽  
Sivakumar Thangavelu ◽  
Nikhitha K Shanmukhan ◽  
...  

Cisplatin (Cis-Diammineplatinum (II) dichloride/CIS) is one of the most potent chemotherapeutic agents widely used in treatment of various cancers. Naringenin (NAR), a natural flavonoid, protect against CIS-induced injury in rats without hampering CIS beneficial cytotoxic activity. Even though NAR exhibits therapeutic potency, clinical evolution of the molecule is embarrassed because of very less aqueous solubility which corresponds to low availability at the site of the tumor. In our former analysis, nanosuspension of naringenin (NARNS) was developed by the method of high-pressure homogenization. The study had been continued to evaluate the protective role of D-α-Tocopheryl polyethylene glycol succinate (TPGS) coated NARNS, against oxidative stress-induced hepato and nephrotoxicity in male Wistar rats upon CIS treatment. Induction of acute hepato and neprotoxicity was done by intraperitoneal injection (i.p) injection of CIS (7 mg/kg of body weight) and administration of NAR and NARNS. Administration of NARNS virtually suppressed CIS-induced and liver injury evidenced by a reduction of lipid peroxidation level, blood urea nitrogen, serum uric acid, creatinine and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, and glutathione peroxidase in rats liver tissue. Histological studies substantiated the biochemical parameters. The study suggests that NARNS has strong hepato and nephroprotective effect compared to NAR.


2017 ◽  
Vol 33 (6) ◽  
pp. 512-518 ◽  
Author(s):  
Seyedeh Missagh Jalali ◽  
Hossein Najafzadeh ◽  
Sadegh Bahmei

This study was performed to assess hepatotoxicity and alterations in liver antioxidant defence in acute lead (Pb) exposure and the protective effects of silymarin in comparison to D-penicillamine in rats. Forty eight Albino rats were divided in eight groups and received the following treatments in a 10-day experiment – group 1: normal saline as control; group 2: 25-mg/kg Pb acetate, intraperitoneally (IP) for the last 5 days; group 3: 100-mg/kg D-penicillamine, IP for the last 5 days; group 4: 200-mg/kg silymarin, orally for 10 days; and groups 5, 6, 7 and 8: in addition to Pb, they received D-penicillamine, for the last 5 days, silymarin for 10 days, a combination of silymarin for 10 days and D-penicillamine for the last 5 days and silymarin for the last 5 days, respectively. Pb acetate exposure induced significant elevation in serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities in group 2 compared to control group. Significant reductions in serum total protein and albumin in all Pb-exposed groups and in serum glucose in groups 2, 6 and 8 were also observed. Liver tissue superoxide dismutase and glutathione peroxidase were significantly lower in groups 2 and 8 compared to control group. Silymarin pretreatment and D-penicillamine administration in groups 5, 7 and 8 could significantly lower ALP, ALT and AST and improve liver antioxidant enzymes. Thus, acute Pb exposure induced hepatotoxicity with suppression of liver antioxidant defence system and silymarin, as an antioxidant could alleviate this effect.


Acetaminophen has contributed to acute liver failure disease in more than half of the USA and Britain but as an analgesic and antipyretic it is very effective. For many decades in Europe, Middle East and Africa, Nigella sativa has been used for various medical purposes, it is part of the botanical family Ranunculaceae of Gently sloping plants, and is called black cumin seed., Nigella sativa conjugated sterols could be used as precursors to many hydrosoluble steroids for hemisynthesis. The aim of the Study is to examine the promising hepatoprotective effects of Nigella sativa against Acetaminopheninduce hepatotoxicity in mice in this experiment Forty adult male albino mice, incorporated in the experiment and Acetaminophenwas used to induce hepatotoxicity in a dose of 1 gm /kg by the oral route. A number of biochemical and histopathological tests have been used to evaluate liver damage and Nigella sativa protective effects. The result showed a significant protective effect of Nigella sativa against acetaminophenhepatotoxic effect as Nigella sativa in this study tended to normalize the serum levels of liver enzymes, and the protective effects observed clearly by the histopathological evaluation confirming that it effectively protected mouse livers against severe damage caused by acetaminophen. Conclusion in our study it shows that Nigella sativa have a very significant protective effects against acetaminophen induced liver toxicity which is recommended to be fully investigation on human especially to people on risk of acetaminophen liver toxicity


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Chiagoziem A. Otuechere ◽  
Sunny O. Abarikwu ◽  
Victoria I. Olateju ◽  
Azeezat L. Animashaun ◽  
Oluwafemi E. Kale

We investigated the protective effects of curcumin on propanil-induced alterations in biochemical indices in blood and liver of male Wistar rats. The study consisted of four treatment groups, with six animals each, designated as control, propanil (20mg/kg), curcumin(50 mg/kg), and curcumin (50 mg/kg) + propanil (20 mg/kg). Rats were administered their respective doses orally, every other day, for 28 days. Propanil administration elicited significant (P<0.001) increases in plasma aspartate aminotransferase and alkaline phosphatase activities, by 24% and 56%, respectively, compared to the control. Treatment with propanil elevated bilirubin, creatinine, and total cholesterol levels in rats, but these were not significant relative to controls. Administration of propanil to rats significantly (P<0.001) increased lipid peroxidation levels. However, catalase activity, vitamin C, and reduced glutathione levels were significantly reduced. Exposure to propanil did not produce any significant changes in packed cell volume, neutrophils, and leukocyte counts. The supplementation of curcumin attenuated the adverse effects of propanil intoxication by reducing lipid peroxidation levels and restored the levels of serum enzymes and reduced glutathione. The present study showed that propanil increased oxidative stress and altered some biochemical parameters in the rats but curcumin could afford some protection to attenuate propanil-induced toxicity in the liver.


2011 ◽  
Vol 44 (13) ◽  
pp. S355
Author(s):  
Esmaeili Amirhossein ◽  
Hajizadeh Moghaddam Akbar ◽  
Chaichi Mohammad Javad ◽  
Ebrahim-Zadeh Mohammad Ali ◽  
Parsian Hadi

Author(s):  
Reyhane Hoshyar ◽  
Ahmadreza Sebzari ◽  
Mohadeseh Balforoush ◽  
Masoomeh Valavi ◽  
Mehran Hosseini

AbstractBackgroundThe adverse effects of methotrexate (MTX) mainly hepatotoxicity restrict its clinical use. This study was designed to investigate the protective effects of saffron (Crocus sativus) (CS) extract on MTX-induced hepatotoxicity.MethodsTwenty-eight male Wistar rats randomly divided into four equal groups. Except for control, all groups received a single intraperitoneal (i.p.) injection of MTX on the 3rd day of study. The CS extract was given (80 mg/kg i.p.) to rats 3 days before MTX and continued for the next 7 days (Pre&Post-CS group) or administrated after MTX injection and lasted for 7 days (Post-CS group). On the 11th day, all rats were sacrificed and their plasma levels of liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined. Also, liver histopathology and hepatic levels of malondialdehyde (MDA), nitric oxide (NO) and super oxidase dismutase (SOD) were evaluated.ResultsThe results showed that MTX significantly incremented plasma levels of AST, ALT, ALP and LDH (all p<0.001) and hepatic MDA and NO levels; whereas, decreased SOD activity. Histological alterations such as early fatty changes were evident in the MTX group. Administration of CS extract at both methods could ameliorate liver enzyme elevation, oxidative/nitrosative stresses and morphological alterations of the liver. Pre-and-post treatment with CS extract showed better protective effects than only post-treatment.ConclusionThe present findings provide showing CS could effectively alleviate MTX-induced hepatotoxicity in rats. Further investigations are recommended to determine the exact mechanisms underlying the hepatoprotective potential of saffron.


Author(s):  
Hala Salah Abdel Kawy Eweis ◽  
Omnyah Mohammad Omar Bashraf ◽  
Ahmed Shaker Ali ◽  
Soad Shaker Ali

Background and Aim: Cisplatin "cis diamminedichloroplatinum [II] (CDDP) is the most widely used drug in cancer chemotherapy and hepatotoxicity is one of its major side effects. Vorinostat (VST) has been recognized to have an antioxidant and anti-inflammatory effect in low doses. The present study aimed to explore the potential protective effects of low dose VST against CDDP induced-liver toxicity in male Wistar rats. Methods: The rats were randomly divided into 4 groups (10 rats each); I-control group, II-CDDP group (7.5 mg/kg I.P. single dose 5 days before the end of the experiment) III-, VST group (15 mg/kg/day by gastric gavage for 28 days) and IV-CDDP + VST group (as in group II & III). Blood and livers samples were collected at the day 28th for biochemical and histopathological examinations. Results: Administration of CDDP significantly decrease hepatic GSH levels and increase serum alanine transaminase, aspartate transaminase and hepatic MDA, p53, TNF-α, and NF-κB levels compared to control. Pretreatment with VST significantly attenuated all unfavorable changes in these parameters. Histopathological analysis showed that VST significantly decreased liver inflammatory and degenerative changes induced by CDDP. VST also significantly increased Bcl-2 and decreased Caspas-3 immunoexpression in hepatic tissues. Conclusion: VST alleviates CDDP induced hepatic toxicity in rats by modulating MDA, p53, TNF-α, and NF-κB. It also significantly increased Bcl-2 and decreased Caspase-3.


2020 ◽  
Vol 26 ◽  
Author(s):  
Abdulqader Fadhil Abed ◽  
Yazun Bashir Jarrar ◽  
Hamzeh J Al-Ameer ◽  
Wajdy Al-Awaida ◽  
Su-Jun Lee

Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05). Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Nesrine S. El Sayed ◽  
Mamdooh H. Ghoneum

Background. Many neurodegenerative diseases such as Alzheimer’s disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective. We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer’s disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods. Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results. Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions. Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.


2010 ◽  
Vol 65 (5-6) ◽  
pp. 419-428 ◽  
Author(s):  
Julia Serkedjieva ◽  
Tsvetanka Stefanova ◽  
Ekaterina Krumova

The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental influenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated. The combined application of HL-SOD and PC in doses, which by themselves do not defend significantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased significantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of influenza virus infection and in general indicate the beneficial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.


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