scholarly journals The combination of lipopolysaccharide and D-galactosamine administration show positive genotoxic effect in mice liver

2020 ◽  
Author(s):  
Wenjing Dong ◽  
Erqun Song ◽  
Yang Song

AbstractLipopolysaccharide (LPS)/D-galactosamine (D-GalN) co-administration induced acute liver injury (ALI) and hepatic fibrosis have been extensively studied. However, whether LPS/D-GalN show genotoxic effect is current unknown. Male mice were divided into eight groups and each group contain eight animals. For the acute administration of LPS/D-GalN, the mice were given a single intraperitoneal (i.p.) injection of LPS/D-GalN (25 μg/kg + 250 mg/kg, 25 μg/kg + 500 mg/kg, 50 μg/kg + 500 mg/kg body weight) for 6 h, respectively. The chronic administration was conduct by the i.p. injection of LPS/D-GalN (10 μg/kg + 100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) injection were used as negative and positive control, respectively. Using single cell gel electrophoresis (SCGE) assay, we found that the acute administration of LPS/D-GalN induces severe DNA damage in mice hepatic cells, but not in brain, sperm and bone marrow cells, implied the genotoxicity of LPS/D-GalN. Interestingly, the chronic treatment of LPS/D-GalN causes significant genotoxic effect in both hepatic and brain cells, but not sperm and bone marrow cells. Histopathological examination in liver and brain section consistent with SCGE results, accordingly. Our study, for the first time, reported the genotoxic potential of LPS/D-GalN co-administration. In addition, LPS/D-GalN administration may serve as an experimental model for further genotoxic study.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjing Dong ◽  
Erqun Song ◽  
Yang Song

AbstractThe acute liver injury (ALI) and hepatic fibrosis caused by the co-treatment of lipopolysaccharide (LPS)/d-galactosamine (D-GalN) have been extensively studied. However, whether LPS/D-GalN are genotoxic has been left unknown. In this study, male mice were divided into eight groups with eight animals in each group. For acute challenge of LPS/D-GalN, the mice in each group received a combination of LPS/D-GalN via intraperitoneal injection at the dose of 25 μg/kg/250 mg/kg, 25 μg/kg/500 mg/kg, or 50 μg/kg/500 mg/kg body weight. An additional group for chronic administration of test compounds was conducted by i.p. injection of LPS/D-GalN (10 μg/kg/100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) given by i.p. injection was used as the negative and positive control, respectively. The results of single cell gel electrophoresis (SCGE) assay indicated that acute exposure of the mice to LPS/D-GalN caused severe DNA damage in hepatic cells, but not in the brain, sperm or bone marrow cells, which evidenced the genotoxicity of LPS/D-GalN administrated in combination. Interestingly, the chronic administration of LPS/D-GalN triggered significant genotoxic effects not only in hepatic but also in brain cells, with negative results in sperm and bone marrow cells. Histopathological examination in the liver and brain tissues revealed changes consistent with the SCGE results. The present study indicates genotoxic potential of LPS/D-GalN co-administered in mice, which may serve as an in vivo experimental model for relevant genotoxic study.


2021 ◽  
Vol 12 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Bin Lin ◽  
Joan T. Smith ◽  
Marsha N. Anderson ◽  
...  

Exposure to ionizing radiation (radiation injury, RI) in nuclear-related episode is evident to be life-threatening. RI occurs at levels of organs, tissues, cytosols, or nucleus. Their mechanisms are still not fully understood. FDA approves pegylated granulocyte colony-stimulating factor (Neulasta™, Peg-G-CSF) for acute hematopoietic syndrome and has been shown to save lives after lethal RI. We aimed to test whether Ghrelin enhanced Peg-G-CSF’s efficacy to save more lives after lethal RI. B6D2F1/J female mice were used for the study. They received 9.5 Gy (LD50/30 at 0.4 Gy/min) emitted from the 60Co-γ-photon radiation facility. Peg-G-CSF was injected subcutaneously at 1 mg/kg once on days 1, 8, and 15 after irradiation. Ghrelin contains 28 amino acid and is a hunger peptide that has been shown to stimulate food intake, promote intestinal epithelial cell proliferation, elevates immunity, inhibits brain hemorrhage, and increases stress-coping. Ghrelin was injected subcutaneously at 113 μg/kg once on days 1, 2, and 3 after irradiation. Survival, body weight, water consumption, hematology, spleen weight, splenocytes, bone marrow cells, and histology of bone marrow and ileum were performed. We observed that radiation resulted in 30-days survival by 30%. RI decreased their body weights and water consumption volumes. On the 30th day post-RI, platelets and WBCs such as basophils, eosinophils, monocytes, lymphocytes, neutrophils and leukocytes were still significantly decreased in surviving mice. Likewise, their RBC, hemoglobin, hematocrit, and splenocytes remained low; splenomegaly was found in these mice. Bone marrow in surviving RI animals maintained low cellularity with high counts of fat cells and low counts of megakaryocytes. Meanwhile, ileum histology displayed injury. However, mice co-treated with both drugs 24 h after RI resulted in 30-days survival by 45% above the vehicle group. Additionally, the body-weight loss was mitigated, the acute radiation syndrome was reduced. This co-therapy significantly increased neutrophils, eosinophils, leukocytes, and platelets in circulation, inhibited splenomegaly, and increased bone marrow cells. Histopathological analysis showed significant improvement on bone marrow cellularity and ileum morphology. In conclusion, the results provide a proof of concept and suggest that the co-therapy of Peg-G-CSF and Ghrelin is efficacious to ameliorate RI.


2005 ◽  
Vol 24 (3) ◽  
pp. 121-127 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Tanveer Beg ◽  
Mohammad Afzal

The genotoxicity of megestrol acetate was studied in mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Megestrol acetate (8.12, 16.25 and 32.50 mg/ kg of body weight) was injected intraperitoneally separately in different groups of animals. Both CAs and SCEs were statistically increased at 16.25 and 32.50 mg/kg of body weight. Our earlier in vitro studies show the generation of free oxygen radicals, by synthetic progestins responsible for the genotoxic damage. As the genotoxic effects of steroids can be reduced by natural products having antioxidant properties, and ascorbic acid possesses antioxidant activity, ascorbic acid (20, 40 or 60 mg/kg of body weight) administered together with megestrol acetate (32.50 mg/kg of body weight) significantly decreased CAs and SCEs, suggesting an antigenotoxic role of ascorbic acid against megestrol acetate induced genotoxic damage in mice bone marrow cells. The antigenotoxic effect was clearly dose dependent. The highest protective effect was observed at 60 mg/kg body weight of ascorbic acid treated with 32.50 mg/kg body weight of megestrol acetate.


2008 ◽  
Vol 93 (4) ◽  
pp. 1398-1401 ◽  
Author(s):  
Brya G. Matthews ◽  
Muhammad A. Afzal ◽  
Philip D. Minor ◽  
Usha Bava ◽  
Karen E. Callon ◽  
...  

Abstract Background: Paget’s disease is a condition of focal accelerated bone turnover. Electron-microscopy investigations of osteoclasts from pagetic lesions have identified nuclear inclusion bodies that have a similar appearance to viral nucleocapsid particles. Subsequently, RNA from several paramyxoviruses has been detected in pagetic tissue, and it was suggested that these viruses, in particular measles, might play a role in the etiology of Paget’s disease. We have tested for measles virus sequences in osteoblasts and bone marrow cells collected from pagetic lesions and healthy bone. Methods: Bone and bone marrow samples were taken from Paget’s patients and control subjects, and cells were cultured from each of these tissues. RNA was extracted from 13 osteoblast cultures and 13 cultures of bone marrow cells derived from pagetic lesions, and from 26 and 23 control osteoblast and bone marrow cultures, respectively. These samples were sourced from 22 patients with Paget’s disease and 31 controls. RT-PCR-nested PCR amplification was used for the detection of the genes for the measles nucleocapsid and matrix proteins. Results: Measles virus sequences were not detected in any of the pagetic or control samples. However, measles virus sequences were identified in samples of a measles virus culture isolate included as a positive control, and in a brain sample from a patient with subacute sclerosing panencephalitis, a condition associated with chronic measles infection. Conclusion: The results of the study do not support the hypothesis that measles virus plays a role in the pathogenesis of Paget’s disease.


CYTOLOGIA ◽  
2005 ◽  
Vol 70 (4) ◽  
pp. 381-384 ◽  
Author(s):  
Om Prakash Chaurasia ◽  
Alok Kumar ◽  
Moushmi Kumari

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Sahdeo Prasad ◽  
Smita Srivastava ◽  
Madhulika Singh ◽  
Yogeshwer Shukla

Glyphosate (N-(phosphonomethyl) glycine,C3H8NO5P), a herbicide, used to control unwanted annual and perennial plants all over the world. Nevertheless, occupational and environmental exposure to pesticides can pose a threat to nontarget species including human beings. Therefore, in the present study, genotoxic effects of the herbicide glyphosate were analyzed by measuring chromosomal aberrations (CAs) and micronuclei (MN) in bone marrow cells of Swiss albino mice. A single dose of glyphosate was given intraperitoneally (i.p) to the animals at a concentration of 25 and 50 mg/kg b.wt. Animals of positive control group were injectedi.p. benzo(a)pyrene (100 mg/kg b.wt., once only), whereas, animals of control (vehicle) group were injectedi.p. dimethyl sulfoxide (0.2mL). Animals from all the groups were sacrificed at sampling times of 24, 48, and 72 hours and their bone marrow was analyzed for cytogenetic and chromosomal damage. Glyphosate treatment significantly increases CAs and MN induction at both treatments and time compared with the vehicle control (P<.05). The cytotoxic effects of glyphosate were also evident, as observed by significant decrease in mitotic index (MI). The present results indicate that glyphosate is clastogenic and cytotoxic to mouse bone marrow.


1999 ◽  
Vol 22 (3) ◽  
pp. 415-417 ◽  
Author(s):  
Lusânia M. Greggi Antunes ◽  
Joana D.C. Darin ◽  
Maria de Lourdes P. Bianchi

The ability of vitamin C (VC) to protect against the clastogenic action of the chemotherapeutic agent cisplatin (DDP, cis-diamminedichloroplatinun II) in rat bone marrow cells was evaluated. DDP was administered to Wistar rats either alone or after treatment with VC. The rats were treated with VC (50, 100 or 200 mg/kg body weight) by gavage 10 min before the administration of DDP (5 mg/kg body weight, ip) and then sacrificed 24 h after treatment. VC significantly reduced (by about 70%) the clastogenicity of DDP in rat bone marrow cells. The antioxidant action of VC presumably modulates the clastogenic action of DDP.


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