Authors:Roxana Stan, Adriana Hangan, Lucia Dican, B. Sevastre, Daniela Hanganu, C. Catoi, Orsolya Sarpataki and Corina Ionescu
Viscum album L. (Santalaceae) (VA) — a parasitic plant that grows on various trees — has proved a significant anticancer effect in both experimental studies and clinical trials. The present study assesses the influence of oxidative stress in mistletoe induced cytotoxicity in tumor cells, in relation to classic cytostatic therapy. VA ethanolic extract was administered alone and combined with doxorubicin (chloride) in Swiss female mice previously intraperitoneally (i.p.) inoculated with Ehrlich tumor cells (1 × 106/animal) that consequently developed Ehrlich ascites carcinoma (EAC). The administered doses were of 50 mg/kg on the 1st, 3rd and 6th day for the VA extract, respectively of 2.5 mg/kg on the 1st and 6th day for doxorubicin, after tumor cell implantation. Fourteen days later all mice were euthanized, ascites of the EAC were collected in order to analyze the tumor proliferation parameters, as well as blood samples, in order to evaluate the antioxidant status in plasma. Tumor development was associated with increased activity of plasma enzymes; classic doxorubicin therapy not only prevents the accumulation of ascitic fluid, but also significantly reduces the activity of plasma antioxidant enzymes. Furthermore, in association with VA extract, the protective effect is improved. Oxidative changes in Ehrlich tumor cells consisted in decreased catalase activity and amplified xanthine oxidase and peroxidase activities.
Authors:Diana Olteanu, A. Filip, A. Mureşan, A. Nagy, F. Tabaran, R. Moldovan, N. Decea, C. Catoi and S. Clichici
Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction.Aim: To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats.Materials and methods: Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index.Results: BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly.Conclusion: BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings.
Authors:Simona Clichici, C. Catoi, T. Mocan, A. Filip, C. Login, A. Nagy, D. Daicoviciu, N. Decea, C. Gherman, R. Moldovan and Adriana Muresan
Oxidative stress is related to the liver fibrosis, anticipating the hepatic stellate cells’ (HSC) activation. Our aim was to correlate oxidative stress markers with the histological liver alterations in order to identify predictive, noninvasive parameters of fibrosis progression in the evolution of toxic hepatitis.CCl4 in sunflower oil was administered to rats intragastrically, twice a week. After 2, 3, 4 and 8 weeks of treatment, plasma levels of malondialdehyde (MDA), protein carbonyls (PC), hydrogen donor capacity (HD), sulfhydryl groups (SH), and glutathione (GSH) were measured and histological examination of the liver slides was performed. Dynamics of histological disorders was assessed by The Knodell score. Significant elevation of inflammation grade was obtained after the second week of the experiment only (p=0.001), while fibrosis started to become significant (p=0.001) after 1 month of CCl4 administration. Between plasma MDA and liver fibrosis development a good correlation was obtained (r=0.877, p=0.05). Correlation between PC dynamics and liver alterations was marginally significant for inflammation grade (r=0.756, p=0.138). HD evolution revealed a marginally inverse correlation with inflammation grade (r=−0.794, p=0.108). No correlations could be established for other parameters with either inflammation grade or fibrosis stage.Our study shows that MDA elevation offers the best prediction potential for fibrosis, while marginal prediction fiability could be attributed to high levels of plasma PC and low levels of HD.