The impact of Crocus sativus stigma against methotrexate-induced liver toxicity in rats

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.

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 102
Author(s):  
Natalia Zaręba ◽  
Klaudia Więcławik ◽  
Rene Kizek ◽  
Bozena Hosnedlova ◽  
Marta Kepinska

This study aimed to synthesise C60–DOX complexes followed by the analysis of their effect on the concentration of metallothionein (MT) as a non-enzymatic antioxidant and on the concentration and activity of superoxide dismutase (SOD) as an antioxidant enzyme in healthy human mammary MCF-10A cells. Dynamic light scattering and electrophoretic light scattering were used to establish the size and zeta potential of the complexes. The MT and SOD concentrations were determined using the ELISA method; SOD activity was determined by tetrazolium salt reduction inhibition. Lower MT concentration following exposure of cells to both DOX and C60 fullerene compared to the control sample was found. However, the concentration of this protein increased as a consequence of the C60–DOX complexes action on MCF-10A cells compared to the control. C60 used alone did not affect the concentration and activity of SOD in MCF-10A cells. Application of free DOX did not activate cellular antioxidant defence in the form of an increase in SOD concentration or its activity. In contrast treatment of cells with the C60–DOX complex resulted in a decrease in SOD1 concentration and a significant increase in SOD activity compared to cells treated with free DOX, C60 and control. Thus, it was found that C60–DOX complexes showed potential for protective effects against DOX-induced toxicity to MCF-10A cells.


1998 ◽  
Vol 26 (03n04) ◽  
pp. 325-332 ◽  
Author(s):  
Cheng-Xiu Li ◽  
Ling Li ◽  
Jung Lou ◽  
Wen-Xiou Yang ◽  
Ting-Wen Lei ◽  
...  

Han-Dan-Gan-Le, a Chinese medicine preparation composed of Salvia miltorrhiza, Radix paeoniae, Astragalus membranaceus, Stephania tetrandra, and dried leaves of Ginkgo biloba, has been used successfully to treat human liver fibrosis and cirrhosis for years. This study was designed to examine the mechanisms of the protection. Male Wistar rats were given CCI4 (1.2 ml/kg, 2 times/week), 20% fat diet, and 30% alcohol in drinking water (every other day) for 6 weeks. Han-Dan-Gan-Le (0.5 and 1.0 g/kg, p.o., daily for 6 weeks) was administered to rats simultaneously to examine the protective effects against CCl4-induced liver fibrosis. The experimentally-induced liver fibrosis and other morphological alterations were significantly ameliorated by Han-Dan-Gan-Le. Han-Dan-Gan-Le treatments decreased CCl4-induced hepatic collagen accumulation by more than 50%, and significantly increased urinary excretion of hydroxyproline. The CCl4-induced lipid peroxidation in liver and serum was ameliorated as a result of Han-Dan-Gan-Le treatment, possibly by restoring the activity of superoxide dismutase activity in liver and erythrocytes, In conclusion, Han-Dan-Gan-Le is effective in protecting against liver fibrosis. The mechanisms of the protection appear to be due to its antioxidant properties and the modulation of hepatic collagen metabolism.


2021 ◽  
Vol 15 (4) ◽  
pp. 233-240
Author(s):  
Reza Kheirandish ◽  
◽  
Mehdi Saberi ◽  
Shahrzad Azizi ◽  
Reza Khakdan ◽  
...  

Background: Oxymetholone, an anabolic-androgenic steroid, has been used to treat some diseases. The abuse of this compound, especially for muscle growth, has severe oxidative side effects on the liver and kidneys. Oxidative stress and free radicals are responsible for the development of various diseases. Phytochemicals are sources of polyphenols, flavonoids, saponins, etc. and may act as scavengers of free radicals. Saffron (Crocus sativus) has considerable antioxidant properties, which may be useful in reversing or preventing these negative effects. Methods: To evaluate the effects of saffron on the liver and kidneys degenerative changes induced by oxymetholone, 24 male Wistar rats were used. The rats were randomly divided into four groups of six rats each as: a) sham (normal saline, 40 mg/kg/day), b) saffron control (40 mg/kg/day), c) oxymetholone (50 mg/rat), and d) treatment group [saffron (40 mg/kg/day)+oxymetholone (50 mg/rat)]. The course of examination was 30 days. Results: After one month, the sham and saffron control groups had normal histological findings. The treatment group with saffron showed a significant reduction in the hepatic and renal degenerative changes induced by oxymetholone compared to those observed in group. Conclusion: Based on the histopathological results, the use of saffron produced protective effects against the degenerative changes in rats’ liver and kidneys induced by oxymetholone.


2007 ◽  
Vol 26 (2) ◽  
pp. 159-167 ◽  
Author(s):  
A. Vanitha ◽  
K. N. Chidambara Murthy ◽  
Vinod Kumar ◽  
G. Sakthivelu ◽  
Jyothi M. Veigas ◽  
...  

Dunaliella bardawil is a carotenoid-producing alga that is being considered for use in nutraceuticals. To evaluate potential protective effects of consumption of this alga, rats were treated with two different doses of D. bardawil (2.5 and 5.0 g kg–1 body weight [bw]) as a biomass suspension daily for 14 days. Animals were tested against Carbon tetrachloride (CCl4; 2 ml kg–1)–induced liver toxicity as measured by various biochemical marker enzymes in liver and blood. All measurements were taken 6 h following the single dose of CCl4. The results of this study show that there was a slight, but statistically significant mean serum enzyme values, with D. bardawil treatment, compared to higher mean values in animals receiving CCl4 alone. Lipid peroxidation is measured by thiobarbituric acid–reactive substance (TBARS) activity was likewise slightly less elevated with algae treatment. The results also demonstrated protection against DNA strand breaks in hepatocytes, as measured by single cell gel electrophoresis. Liver histopathology was less severe with D. bardawil treatment, supporting the apparent protective action of 14-day treatment on hepatic oxidative injury.


2016 ◽  
Vol 86 (1-2) ◽  
pp. 27-35 ◽  
Author(s):  
Burcu Gul Baykalir ◽  
Dilek Aksit ◽  
Mustafa Selim Dogru ◽  
Arzu Hanım Yay ◽  
Hasan Aksit ◽  
...  

Abstract. Inflammatory bowel disease (IBD) is an inflammatory disorder involving colitis. Lycopene is a naturally occurring carotenoid that has attracted considerable attention as a potential chemopreventive agent. The impact of lycopene on colitis is currently unknown. The aim of this study was to investigate the protective effects of lycopene in a rat model of colitis induced by acetic acid. The animals were randomly divided into the following five groups: the control group, colitis group, colitis + sulfasalazine group as a positive control group, colitis + lycopene and lycopene groups. Colonic mucosal injury was assessed by biochemical and histopathological examinations. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), ceruloplasmin (CPN), total sialic acid and iron (Fe) levels were evaluated in blood samples. MDA, SOD, TAS and DNA fragmentation levels were also measured in colon tissues. MDA (p < 0.05), total sialic acid (p < 0.05) and DNA fragmentation levels (p < 0.01) were significantly higher, and the activity of the antioxidant enzyme were lower in the colitis group than in the control group. Treatments with lycopene in the colitis decreased MDA, total sialic acid and DNA fragmentation levels, while SOD activity (p < 0.05), TAS (in colon p < 0.05; in serum p < 0.01), CPN (p < 0.05) and Fe levels (p < 0.05) were significantly increased. The histopathological evaluation also confirmed the foregoing findings. Treatment with lycopene ameliorated the biochemical and pathological alterations caused by colitis. The results obtained in this study indicate that lycopene may exert protective effects in experimental colitis and might, therefore, be useful for treatment of IBD.


2019 ◽  
Vol 8 (2) ◽  
pp. 127-132 ◽  
Author(s):  
Soodabeh Zendeboodi ◽  
Abdolhamid Esmaili ◽  
Ali Movahed ◽  
Hossein Fatemikia ◽  
Ali Jamshidi ◽  
...  

Introduction: Resveratrol (trans-3,5,4’-trihydroxystilbene) as a polyphenol with potential antioxidant and anti-inflammatory properties is known as an effective herbal medicine in different disorders in rats. Objectives: The present study was carried out to investigate the protective effects of oral consumption of resveratrol on vanadium induced renal injury in male Wistar rats. Materials and Methods: Animals received either ammonium metavanadate (AMV, 5 mg/ kg/d, (intraperitoneally; 14 consecutive days) or resveratrol solution (10 mg/kg and 50 mg/kg, gastric gavage) along with AMV treatment. The last group received resveratrol alone (50 mg/ kg, gastric gavage) for 4 weeks. Results: AMV injection caused progressive tubular damages resembling acute tubular necrosis. Microscopic views revealed tubular attenuation and blebbing. In addition, progressive peritubular congestion of the capillaries observed while no evidence of renal fibrosis was present in trichrome staining. Further, levels of the renal transforming growth factor β1 (TGF-β1) as an index of fibrosis had no difference in treated animals as compared with the control (13.4±1.2 versus 11.24±0.93 pg/mg protein) at the P<0.05. However, in AMVtreated animals receiving the higher dose of resveratrol (50 mg/kg), the renal superoxide dismutase (SOD) activity, showed no difference as compared with the saline-treated rats (42±1.3 versus 51±1.4). Conclusions It is evident that AMV injection had no ability to induce renal fibrosis in rats while it evokes renal destructive lesions based on pathological results and enzyme levels. Moreover, our preliminary results suggest that resveratrol in high dose (50 mg/kg) could confer a minor role against AMV induced renal tubular necrosis in rats due to pathological results.


2021 ◽  
Vol 21 (2) ◽  
pp. 81-88
Author(s):  
ETRINA MELINDA ◽  
ERMI GIRSANG ◽  
ALI NAPIAH NASUTION

Doxorubicin as a chemotherapy agent is most widely used in cancer treatment. Long-term use at a predetermined dose has a side effect, namely cardiotoxicity. Doxorubicin-induced cardiotoxicity is considered to be caused by reactive oxygen species (ROS), which is also characterized by increasing CK-MB enzyme levels in the blood. To reduce the impact of doxorubin-induced toxicity, a study was conducted on natural antioxidant sources with cardioprotective capabilities in vivo. Phyllanthus emblica L. fruit was used as a sample for a natural source of antioxidants extracted using ethanol. Then performed a phytochemical screening of secondary metabolites contained in it. This extract was administered orally in various doses to the experimental animal Wistar rats and the induced doxorubicin to these animals. The CK-MB enzyme levels were measured, and the heart organ histopathology test was performed. The results of this study indicate that P. emblica L. fruit extract contains alkaloids, tannins, flavonoids, terpenoids, phenolics, and triterpenoids compounds. Extract treatment at a 400 mg/kg BW dose showed the best reduction in CK-MB levels with great improvements in regular arrangement and shape of myocardial muscle cells of cardiac tissue. The sample extract at a 400 mg/kg BW dose showed remarkably decreasing of CK-MB great improvements of heart tissue on doxorubicin-induced cardiotoxicity. This study showed the potential protective effect of P. emblica L. against doxorubicin-induced cardiotoxicity.


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.


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.


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.


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