The hepatoprotective and antioxidative effect of saffron stigma alcoholic extract against vincristine sulfate induced toxicity in rats

AbstractVincristine (VCR) is an important anti-cancer drug, which is highly toxic for the liver. This study aimed at evaluating the protective effect of alcoholic extract of saffron stigma against vincristine hepatotoxicity in the rat. A total number of 50 rats were randomly divided into 10 groups, including controls, rats receiving 0.25 mg/kg (A group), 0.5 mg/kg (B group), 0.75 mg/kg (C group) VCR, 0.25 mg/kg VCR + 0.5 mg/kg saffron (D group), 0.5 mg/kg VCR + 0.5 mg/kg saffron (E group), 0.75 mg/kg VCR + 0.5 mg/kg saffron (F group), 0.25 mg/kg VCR + 1mg/kg saffron (G group), 0.5 mg/kg VCR + 1 mg/kg saffron (H group), and 0.75 mg/kg VCR + 1 mg/kg saffron (I group) groups. Serum level of liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin were measured using specific kits at the end of the experimental period. Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) values were measured using ferric reducing antioxidant of power (FRAP) and thiobarbituric acid reaction (TBAR) methods, respectively. Administration of VCR, especially at the concentration of 0.75mg/kg, caused severe hepatic injury with significant increase in the levels of AST (582.0±39.45 UI), ALT (124.0±5.92 UI), ALP (939.8±89.8 UI) enzymes and bilirubin (0.17±0.008). VCR administration also significantly increased the serum MDA level (0.49±0.021 nmol/ml), while TAC value was declined significantly (241.27±18.27 μmol/l). These effects were dose-dependent. Treatment with saffron extract decreased the activity of liver enzymes and MDA values in hepatotoxic rats with a significant enhancement in serum TAC content. These effects were notable for rats that received 1mg/kg plant extract. Administration of saffron, especially at higher concentration, can reduce VCR-induced hepatotoxicity, antioxidant depletion and lipid peroxidation, presumably due to its antioxidative properties.

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The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine

Biochemical Journal ◽

10.1042/bcj20160302 ◽

2016 ◽

Vol 473 (17) ◽

pp. 2635-2643 ◽

Cited By ~ 14

Author(s):

Cristina E. Requena ◽

Guiomar Pérez-Moreno ◽

András Horváth ◽

Beáta G. Vértessy ◽

Luis M. Ruiz-Pérez ◽

...

Keyword(s):

Thymidylate Synthase ◽

Cellular Response ◽

Dna Demethylation ◽

Cancer Drug ◽

Dependent Manner ◽

Strand Breaks ◽

Anti Cancer ◽

Synthase Inhibitor ◽

Dose Dependent ◽

Cytotoxic Mechanism

Decitabine (5-aza-2′-deoxycytidine, aza-dCyd) is an anti-cancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukaemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 (dCTP pyrophosphatase 1) and dUTPase are two ‘house-cleaning’ nucleotidohydrolases involved in the elimination of non-canonical nucleotides. In the present study, we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase, thus suggesting their contribution to the cellular response to this anti-cancer nucleoside. We present several lines of evidence supporting that, in addition to the formation of aza-dCTP (5-aza-2′-deoxycytidine-5′-triphosphate), an alternative cytotoxic mechanism for decitabine may involve the formation of aza-dUMP, a potential thymidylate synthase inhibitor. Indeed, dUTPase or DCTPP1 down-regulation enhanced the cytotoxic effect of decitabine producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA. Moreover, DCTPP1 hydrolyses the triphosphate form of decitabine with similar kinetic efficiency to its natural substrate dCTP and prevents decitabine-induced global DNA demethylation. The data suggest that the nucleotidohydrolases DCTPP1 and dUTPase are factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy.

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Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks

Laboratory Animal Research ◽

10.1186/s42826-019-0015-z ◽

2019 ◽

Vol 35 (1) ◽

Cited By ~ 1

Author(s):

Mi Ju Kang ◽

Ji Eun Kim ◽

Ji Won Park ◽

Hyeon Jun Choi ◽

Su Ji Bae ◽

...

Keyword(s):

Animal Models ◽

Tumor Tissue ◽

Tumor Model ◽

Cancer Drug ◽

Dependent Manner ◽

Cancer Drugs ◽

Ki 67 ◽

Anti Cancer ◽

Dose Dependent ◽

Syngeneic Model

Abstract In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used in immunological studies. In this study, the C57BL/6NKorl stock and two other commercial stocks (C57BL/6NA and C57BL/N6B) are evaluated by comparing the occurrence of tumors using the syngeneic model; furthermore, we compare the response to anti-cancer drugs in the syngeneic model by evaluating survival, growth of tumors, proliferation and molecular biology analysis. In the syngeneic model using LLC (Lewis lung carcinoma) cells, the survival of mice and growth of the tumor showed a better response in the C57BL/6NKorl stock, and was dependent on the cell concentration of the dosing tumor, as compared to the other C57BL/6N stocks. However, the Ki-67 staining showed only little difference in cell proliferation within the tumor tissue each mouse stocks. Comparing the sensitivity to anti-cancer drug by examining changes in growth, volume and weight revealed that cisplatin treatment for tumor-bearing C57BL/6NKorl was more dependent on concentration. The Ki-67 staining, however, showed no difference among the C57BL/6N stocks after cisplatin treatment. The expressions of p27 and p53 tumor suppressor proteins, caspase-3 and Bax showed dose-dependent increase after exposure to cisplatin, whereas the expression of Bcl-2 was reduced in a dose-dependent manner. Furthermore, the expressions of MMP-2 and VEGF involved in metastasis, as well as inflammatory genes IL-1β, IL-6 and IL-10, showed dose-dependent decrease in tumor tissue after cisplatin exposure. Differences observed among the C57BL/6N stocks were not significant. Taken together, our studies reveal that C57BL/6NKorl has the potential of being a useful biological resource established in Korea, as it does not differ from the two commercially available C57BL/6N stocks when considering response to tumor generation and sensitivity to anti-cancer drugs using the syngeneic tumor model.

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The Synthesis of Nano-Doxorubicin and its Anticancer Effect.

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666201229115612 ◽

2020 ◽

Vol 21 ◽

Author(s):

Lusha Zhu ◽

Mei Lin

Keyword(s):

Side Effects ◽

Clinical Application ◽

Cancer Drug ◽

Multi Drug Resistance ◽

Anticancer Effect ◽

First Line ◽

Anti Cancer ◽

Tumor Specificity ◽

New Research ◽

Dose Dependent

Doxorubicin (DOX) is widely used as a clinical first-line anti-cancer drug. However, its clinical application is severely limited due to the lack of tumor specificity of the drug and severe side effects such as myelosuppression, nephrotoxicity, dose-dependent cardiotoxicity, and multi-drug resistance. To improve the bioavailability of DOX, maximize the therapeutic effect, and reduce its toxic and side effects, many studies have been done on the nanoformulations of DOX, such as liposomes, polymer micelles, dendrimer, nanogels. Herein, we review the latest progress of DOX nano-preparations and their anti-tumor effects, hoping to provide theoretical references and new research ideas for the development of new dosage forms of the drug and the technical methods available for clinical application.

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The Influence of Naringin on the Oxidative State of Rats with Streptozotocin- Induced Acute Hyperglycaemia

Zeitschrift für Naturforschung C ◽

10.1515/znc-2004-9-1018 ◽

2004 ◽

Vol 59 (9-10) ◽

pp. 726-733 ◽

Cited By ~ 38

Author(s):

M. Ali Mamdouh ◽

A. Abd El Kader Monira

Keyword(s):

Antioxidant Activity ◽

Body Weight ◽

Total Antioxidant Status ◽

Thiobarbituric Acid ◽

Diabetic Rats ◽

Antioxidant Enzyme Activities ◽

Significant Amelioration ◽

Total Antioxidant ◽

Dose Dependent Decrease ◽

Dose Dependent

Abstract The effect of various doses (0, 10, 20, 40, or 80 mg/kg body weight) of naringin (a citrus flavonone) was studied on streptozotocin (STZ)-induced hyperglycaemic rats to evaluate the possible hypoglycaemic and antioxidant activity of naringin in diabetes. In comparison to the normoglycaemic group the treatment of rats with a single dose of STZ (65 mg/kg body weight) only revealed a significant increase (P < 0.05) in plasma hydrogen peroxide (H2O2) by 230%, increased the thiobarbituric acid reactive substances (TBARS) as index of the lipid peroxidation level by 69%, while total antioxidant activity was decreased by 36%, with a consistent significant decrease (P < 0.05) in the activity of erythrocytes antioxidative enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and paraoxonase (PON). Exogenous administration of individual gradual doses of naringin to hyperglycaemic rats causes a dose-dependent decrease of the glucose level, an increase of the insulin concentration, a decrease of the H2O2 and TBARS levels, as well as the increase of the total antioxidant status with an increase of antioxidant enzyme activities (CAT, SOD, GPx, and PON). From this study, it may be concluded that all doses of naringin provided a significant amelioration of hypoglycaemic and antioxidant activity in STZ-induced diabetic rats, however, the greatest effect of naringin was observed at 80 mg/kg body weight.

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Study the effect of a new nikel (II) Complex and anticancer drug (cp) on Liver enzyme activity (GPT,GOT) and Creatinine level in Kidney of femal mice

Baghdad Science Journal ◽

10.21123/bsj.11.3.1100-1106 ◽

2014 ◽

Vol 11 (3) ◽

pp. 1100-1106

Author(s):

Baghdad Science Journal

Keyword(s):

Enzyme Activity ◽

Creatinine Level ◽

Liver Enzyme ◽

Liver Enzymes ◽

Cancer Drug ◽

Inhibition Rate ◽

Liver Enzyme Activity ◽

Maximum Inhibition ◽

Anti Cancer ◽

Maximum Activation

This study involved the effect of anew nickel (II) complexs with formla [NiL2(H2O)2].2.5ETOH where L=Bis[5-(p-nitrophenyL)-4-phenyL-1,2,4-traizole-3-dithocarbamato hydrazide] diaqua. nickel(II). Ethanol(2.5).and anti-cancer drug cyclophosphamide on specific actifity of two Liver enzymes (GOT,GPT) in the (Liver,kidney) tissues and on the creatinine Level in the kidney byUtilizing an invivosystem in femalmice.The result showed that inhibition in the activity of GPT and GOT enzymes in theLiver and in both nickel (II) complex and cyclophosphamide drug (CP) . mice weretreated with three doses (90,180,320) µg/mouse for three days for each group.The Liver show's the highest rate of GPT inhibition was about 97.43% at180µg/mouse regarding the kidney the inhibition rate was about 98.63% at 180µg/mouse .The maximum inhibition of GOT enzame in the Liver was about 77. 48% ataconcentration 180µg/mouse and the inhbition rate of GOT enzyme in the kidney was about 97.87% at aconcentration 320µg/mouse.The result showed the effect of nickel (II) complex on the creatinine Level in the kidney ,The maximum activation was about 99.45% at 320µg/mouse.

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Combined Analysis of Gut Microbiota and Plasma Metabolites Reveals the Effect of Red-Fleshed Apple Anthocyanin Extract on Dysfunction of Mice Reproductive System Induced by Busulfan

Frontiers in Nutrition ◽

10.3389/fnut.2021.802352 ◽

2022 ◽

Vol 8 ◽

Author(s):

Bin Wang ◽

Jihua Xu ◽

Shenhui Jiang ◽

Yanbo Wang ◽

Jun Zhu ◽

...

Keyword(s):

Gut Microbiota ◽

Reproductive System ◽

Cancer Drug ◽

Plasma Metabolites ◽

Anthocyanin Content ◽

Treatment Groups ◽

Genes Expression ◽

Anti Cancer ◽

Total Antioxidant ◽

Gut Microbial Community

Busulfan is currently an indispensable anti-cancer drug, but the side effects on male reproductive system are so serious. Meanwhile, red-fleshed apples are natural products with high anthocyanin content. In this research, we analyzed the effect of red-fleshed apple anthocyanin extract (RAAE) on busulfan-treated mice. Compared with the busulfan group, main plasma biochemical indicators were significantly improved after RAAE treatment. Compared with BA0 (busulfan without RAAE) group, total antioxidant capacity(T-AOC) and the activity of superoxide dismutase (SOD) and glutathione catalase (GSH-Px) in RAAE treatment groups were obviously increased, while the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly decreased. Malondialdehyde (MDA) was significantly decreased in the RAAE groups. In addition, we found RAAE alleviated busulfan-disrupted spermatogenesis through improving genes expression which are important for spermatogenesis, such as DDX4, PGK2, and TP1. Furthermore, we found that RAAE increased beneficial bacteria Akkermansia and Lactobacillaceae, and significantly depleted harmful bacteria Erysipelotrichia. The correlation studies indicated that RAAE ameliorated busulfan-induced rise in LysoPC levels through regulating gut microbial community and their associated metabolites. In conclusion, this study extends our understanding of the alleviated effect of RAAE on busulfan-induced male reproductive dysfunction through regulating the relationships between gut microbiota and metabolites.

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A study of the effect of new cobalt (II) complex and cyclophosphamide drug on (GPT, ALP) activity by using in vivo system

Baghdad Science Journal ◽

10.21123/bsj.12.3.555-562 ◽

2015 ◽

Vol 12 (3) ◽

pp. 555-562

Author(s):

Baghdad Science Journal

Keyword(s):

Liver Enzymes ◽

Specific Activity ◽

Cancer Drug ◽

High Activation ◽

Female Mice ◽

Alp Activity ◽

Anti Cancer ◽

Maximum Activation

The present work involved a study the effect of cobalt(II) complex with formula [CoL(H2O)NO3] .4ETOH where L=Nitro [5-(P-nitro phenyl) -4-phenyl-1,2,4 traizole-3-dithiocarbamato hydrazide] aqua. (4) Ethanol and anti-cancer drug - cyclophosphamide on specific activity of two liver enzymes (GPT,ALP) by utilizing an in vivo system in female mice. On the enzymatic level an inhibition in the activity of GPT was noticed in different body organs such as liver, kidney and lung. The inhibition was noticed in both test and cyclophosphamide drug (cp). Mice were treated with three doses of cyclophosphamide (90,180, 250) ?g/ mouse for three days. The same doses were used for the cobalt (II) complex. The liver shows the highest rate of(GPT) inhibition compared to other organs. The ratio was about 90% at three doses of cobalt (II) complex, this ratio was similar to ratio inhibition of cyclophosphamide at the same doses. On the contrary the enzyme ALP showed high activation in different organs such as liver, kidney and lung in both groups, test and cyclophosphamide drug (cp) at the three doses (90, 180, 250) ?g /mouse. The result showed the highest ratio of activation in the kidney comparable with other organs. The maximum activation of cobalt(II) complex was about 1198% at a concentration 180µg/mouse.There are significant differences(P

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