Journal article
Influence of Hyperglycaemia on Chemical-Induced Toxicity: Study with Cyclophosphamide in Rat
Basic & clinical pharmacology & toxicology, Vol.105(4), pp.236-242
10/01/2009
DOI: 10.1111/j.1742-7843.2009.00433.x
PMID: 19497016
Abstract
Diabetes mellitus is a metabolic disorder characterized by elevated level of glucose in the blood. Hyperglycaemia perturbs the critical balance between oxidative stress and anti-oxidant defence mechanisms in the body and thereby alters the response of biological system towards various toxic chemicals. Cyclophosphamide (CP) is a widely prescribed anticancer drug, well-known genotoxic agent as well as used in the development of immunocompromised animal models. The present study investigated the modulating effect of diabetes on the cyclophosphamide-induced cytotoxicity and genotoxicity. The study was performed on male Sprague-Dawley rats (200 +/- 10 g). Cyclophosphamide (10 mg/kg) was administered five consecutive days in a week for 3 weeks to both control and diabetic rats. Thiobarbituric acid reactive substances (TBARS) levels were measured in the plasma, liver, kidney and lung tissues. DNA damaging potential of cyclophosphamide under diabetic condition was evaluated using comet and halo assay as an endpoint. To further ascertain the mode of cell death, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay and immunohistochemical evaluation of p53 was performed. Significant increase in DNA damage was revealed by the comet assay parameters, halo assay indicated the level of cytotoxicity and the oxidative stress was measured using the TBARS assay in the diabetic rats receiving cyclophosphamide treatment. The toxic effects were more prominent in diabetic animals as compared to non-diabetic rats. Cyclophosphamide treatment and diabetic condition per se led to increase in the p53 + and TUNEL + cells in the liver and kidney of rats. Under diabetic condition, further increase in the p53 + and TUNEL + cells was observed in response to cyclophosphamide. In the present study, we report that hyperglycaemic condition exaggerates the cyclophosphamide-induced toxicity and the response was found to be tissue specific.
Details
- Title: Subtitle
- Influence of Hyperglycaemia on Chemical-Induced Toxicity: Study with Cyclophosphamide in Rat
- Creators
- Kalavatala Saandeep - National Institute of Pharmaceutical Education and ResearchAjit Vikram - National Institute of Pharmaceutical Education and ResearchDurga Nand Tripathi - National Institute of Pharmaceutical Education and ResearchPoduri Ramarao - National Institute of Pharmaceutical Education and ResearchGopabandhu Jena - National Institute of Pharmaceutical Education and Research
- Resource Type
- Journal article
- Publication Details
- Basic & clinical pharmacology & toxicology, Vol.105(4), pp.236-242
- DOI
- 10.1111/j.1742-7843.2009.00433.x
- PMID
- 19497016
- NLM abbreviation
- Basic Clin Pharmacol Toxicol
- ISSN
- 1742-7835
- eISSN
- 1742-7843
- Publisher
- Wiley
- Number of pages
- 7
- Language
- English
- Date published
- 10/01/2009
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359908002771
Metrics
12 Record Views