scholarly journals Antioxidant and Anti-Inflammatory Effects of Diallyl Disulfide on Hepatotoxicity Induced by Cyclophosphamide in Rats

2020 ◽  
Vol 15 (10) ◽  
pp. 1934578X2096908
Author(s):  
Hesham Farouk Hasan ◽  
Gehan Roushdy Abdel-Hamid ◽  
Sahar Ismail Ebrahim

Diallyl disulfide (DADS) is a garlic-derived organo-sulfur compound. This study was carried out to investigate the protective potential, antioxidant, and anti-inflammatory effects of this compound against cyclophosphamide (CP)-induced hepatotoxicity in rats. A single intraperitoneal dose of CP (200 mg/kg) resulted in a significant disturbance in hepatic function and oxidative stress, as well as inflammatory biomarkers. In addition, histopathological examination showed distinct changes and increased expression of proliferating cell nuclear antigen in hepatocytes. On the other hand, daily oral preadministration of DADS (200 mg/kg) for 10 days before the CP dose effectively attenuated the hepatotoxicity caused by CP administration as confirmed by significant amelioration of the aforementioned parameters in rat’s liver. It could be concluded that administration of DADS can diminish CP-induced hepatotoxicity through concurrent upregulation of antioxidant and anti-inflammatory responses that denote its possible potential clinical application against side effects of the CP drug.

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhihui Jiao ◽  
Yajun Ma ◽  
Xiaoning Liu ◽  
Yansong Ge ◽  
Qianzhen Zhang ◽  
...  

Aim. To study the anti-inflammatory and liver regenerative effects of adipose-derived mesenchymal stem cells (ADSCs) on a porcine model of ischemia-reperfusion (IR) and hemihepatectomy. Methods. Eighteen healthy Bama miniature pigs were randomly divided into the sham-operated (sham), untreated IR injury (IRI), and ADSC-transplanted (ADSC) groups. Hepatic IR was established by laparoscopic hemihepatectomy. ADSCs were transplanted directly into the liver parenchyma after the surgery. Hepatic inflammation and liver regeneration were evaluated by histopathological examination and assessment of relevant cytokines and other factors. Results. ADSC transplantation successfully ameliorated the IRI-induced histopathological damage and the high levels of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α. In addition, the ADSCs enhanced the expression of the anti-inflammatory IL-10, regenerative factors including HGF, Cyclin D1, and proliferating cell nuclear antigen (PCNA), and angiogenic factors like VEGF, ANG-1, and ANG-2. Conclusions. ADSCs attenuated the hepatic IRI-induced inflammatory response and promoted liver regeneration.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Isaac J. Morrison ◽  
Jianan Zhang ◽  
Jingwen Lin ◽  
JeAnn E. Murray ◽  
Roy Porter ◽  
...  

AbstractColorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC–MS–DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.


2014 ◽  
Vol 21 (9) ◽  
pp. 1240-1245 ◽  
Author(s):  
M. T. Nieminen ◽  
M. Hernandez ◽  
L. Novak-Frazer ◽  
H. Kuula ◽  
G. Ramage ◽  
...  

ABSTRACTChronic biofilm infections are often accompanied by a chronic inflammatory response, leading to impaired healing and increased, irreversible damage to host tissues. Biofilm formation is a major virulence factor forCandida albicansand a challenge for treatment. Most current antifungals have proved ineffective in eradicating infections attributed to biofilms. The biofilm structure protectsCandidaspecies against antifungals and provides a way for them to evade host immune systems. This leads to a very distinct inflammatory response compared to that seen in planktonic infections. Previously, we showed the superior efficacy ofdl-2-hydroxyisocaproic acid (HICA) against various bacteria and fungi. However, the immunomodulatory properties of HICA have not been studied. Our aim was to investigate the potential anti-inflammatory response to HICAin vivo. We hypothesized that HICA reduces the levels of immune mediators and attenuates the inflammatory response. In a murine model, a robust biofilm was formed for 5 days in a diffusion chamber implanted underneath mouse skin. The biofilm was treated for 12 h with HICA, while caspofungin and phosphate-buffered saline (PBS) were used as controls. The pathophysiology and immunoexpression in the tissues surrounding the chamber were determined by immunohistochemistry. Histopathological examination showed an attenuated inflammatory response together with reduced expression of matrix metalloproteinase 9 (MMP-9) and myeloperoxidase (MPO) compared to those of chambers containing caspofungin and PBS. Interestingly, the expression of developmental endothelial locus 1 (Del-1), an antagonist of neutrophil extravasation, increased after treatment with HICA. Considering its anti-inflammatory and antimicrobial activity, HICA may have enormous therapeutic potential in the treatment of chronic biofilm infections and inflammation, such as those seen with chronic wounds.


Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3084 ◽  
Author(s):  
Gaoqing Xu ◽  
Jing Zhao ◽  
Hongyu Liu ◽  
Jun Wang ◽  
Wenfa Lu

The purpose of the present study is to examine the effects of melatonin on apoptosis and oxidative stress in mouse Leydig cells and to elucidate the mechanisms responsible for these effects. Our results indicated that 10 ng/mL of melatonin significantly promoted cell viability, the ratio of EdU-positive (5-Ethynyl-2′-deoxyuridine) cells, and increased the mRNA expression of proliferating cell nuclear antigen (PCNA), cyclin D1(CCND1), and cell division control protein 42 (CDC42) (p < 0.05). We also observed that melatonin inhibited apoptosis of mouse Leydig cells, accompanied with increased B-cell lymphoma-2 (BCL-2) and decreased BCL2 associated X (BAX) mRNA and protein expression. Moreover, addition of melatonin significantly decreased the reactive oxygen species (ROS) production and malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, while it increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels (p < 0.05). In addition, we also found that melatonin increased the expression of SIRT1 (Silent information regulator 1) (p < 0.05). To explore the role of SIRT1 signaling in melatonin-induced cells, mouse Leydig cells were pretreated with EX527, an inhibitor of SIRT1. The protective effects of melatonin on mouse Leydig cells were reversed by EX527, as shown by decreased cell proliferation and increased cell apoptosis and oxidative stress. In summary, our results demonstrated that melatonin inhibited apoptosis and oxidative stress of mouse Leydig cells through a SIRT1-dependent mechanism.


2014 ◽  
Vol 59 (No. 5) ◽  
pp. 265-269
Author(s):  
E. Ozenc ◽  
MF Bozkurt

This study was conducted on a three-year-old Sphynx breed female cat which was brought to the clinic for masses on the teats. The medical history showed that these masses had developed slowly within the period of six months to one year. Following the clinical examination, these masses were removed via surgery. They were between 0.6 cm and 1.5 cm in diameter. Ulcer areas 2 mm to 5 mm in size were observed over the skin. Their sectional surface was uniformly grayish in colour. Histopathological examination of the masses revealed that the cells originated from the glandular duct and had given rise to hyperplasia; connective tissue was densely attached to the masses. Moreover, inflammatory changes and areas of ulceration were observed. Immunohistochemical analysis showed that the cells surrounding the epithelial hyperplasia were vimentin-positive and the proliferative activity of epithelial cells was measured to be 50% by analysis of proliferating cell nuclear antigen (PCNA). Based on clinical, histological and immunohistochemical findings, it was found the masses were diagnosed as atypical fibroepithelial hyperplasia. This case is the first to present a fibroepithelial hyperplasia in the teats of a cat. &nbsp; &nbsp;


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Daixiu Yuan ◽  
Tarique Hussain ◽  
Bie Tan ◽  
Yanhong Liu ◽  
Peng Ji ◽  
...  

This study was designed to evaluate the antioxidant and anti-inflammatory effects ofEucommia ulmoidesflavones (EUF) using diquat-challenged piglet models. A total of 96 weaned piglets were randomly allotted to 1 of 3 treatments with 8 replication pens per treatment and 4 piglets per pen. The treatments were basal diet, basal diet + diquat, and 100 mg/kg EUF diet + diquat. On day 7 after the initiation of treatment, the piglets were injected intraperitoneally with diquat at 8 mg/kg BW or the same amount of sterilized saline. The experiment was conducted for 21 days. EUF supplementation improved the growth performance of diquat-treated piglets from day 14 to 21. Diquat also induced oxidative stress and inflammatory responses and then impaired intestinal morphology. But EUF addition alleviated these negative effects induced by diquat that showed decreasing serum concentrations of proinflammatory cytokines but increasing antioxidant indexes and anti-inflammatory cytokines on day 14. Supplementation of EUF also increased villi height and villous height, crypt depth, but decreased the histopathological score and MPO activity compared with those of diquat-challenged pigs fed with the basal diet on day 14. Results indicated that EUF attenuated the inflammation and oxidative stress of piglets caused by diquat injection.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hua Sun ◽  
Linghong Yu ◽  
Huailing Wei ◽  
Gengtao Liu

Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN-) initiated and phenobarbital- (PB-) promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg) before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC) and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg) at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and α-fetal protein (AFP) in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg) animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.


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