Abstract
BackgroundCadmium is one of the inflammation-related xenobiotics and has been regarded as a potent carcinogen. The relationship between inflammation and cell proliferation due to chronic infection has been studied, but the mechanism is not fully clear. Though the mode of cadmium toxicity is well characterized in animal cells, still it requires some further investigations. Previously we reported that cadmium induces immune cell death in Swiss albino mice. In the present study we showed that instead of inducing cell death mechanism, cadmium in low concentration triggers proliferation in mice lung cell and our results reveals that prior to the induction of proliferation it causes severe inflammation.MethodsSwiss albino mice were treated with different concentrations of cadmium to determine the LD50. Mice were subdivided (5 mice each) according to the exposure period (15, 30, 45, 60 days) and were given sub lethal dose (5 mg/Kg body weight) of cadmium chloride and ibuprofen (50 mg/Kg body weight, recommended dose) once in a week. SEM and histology were performed as evidence of changes in cellular morphology. Inflammation was measured by the expression of Cox-2 and MMPs. Expression of proinflammatory cytokines (Cox-2, IL-6), signaling and cell cycle regulatory molecules (STAT3, Akt, CyclinD1) were measured by western blot, ELISA and immunoprecipitation. Mutagenecity was evidenced by comet assay. Cell proliferation was determined by cell count, cell cycle and DNA analysis.ResultsProlonged exposure of low concentration of cadmium resulted in up regulation of proinflammatory cytokines and cell cycle regulatory molecules. Though NSAIDs like Ibuprofen reduces the expression of inflammatory cytokines, but it did not show any inhibitory effect on cadmium adopted lung cell proliferation.ConclusionOur results prove that cadmium causes both inflammation and cell proliferation when applied in a low dose but proliferative changes occur independent of inflammation.
Highlights
Cadmium is one of the inflammation-related xenobiotics and has been regarded as a potent carcinogen
Due to cadmium exposure, expression of IL-6, STAT3 and inflammatory enzyme matrix metalloproteinases (MMP)-2, Cox-2 increased significantly
It was found that 50% of the experimental population died at a concentration of about 10 mg/Kg body weights, (Fig. 1) and there is a significant decrease (p < 0.05) of survival according to the increasement of dose
Summary
Cadmium is one of the inflammation-related xenobiotics and has been regarded as a potent carcinogen. In the present study we showed that instead of inducing cell death mechanism, cadmium in low concentration triggers proliferation in mice lung cell and our results reveals that prior to the induction of proliferation it causes severe inflammation. Chronic exposure to Cadmium has been associated with a number of physiological consequences such as renal failure and immunosuppression as well as various types of cancers in mammals. Several toxicities such as hepatoxicity, neurotoxicity and cardiotoxicity are documented under high Cadmium exposure [3,4]. Following various routes of exposure to Cadmium, experimental animals produce tumors of multiple organs [9,10]. Despite being one of the major routes for cadmium absorption, the toxic mechanism of cadmium on lung tissue is still poorly understood [11]
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