Exposure of Nicotine in Neonatal Rats Induces Activated Inflammatory Cytokines and Altered Biomarkers Related to Cardiac Dysfunction

Background and Objectives: Nicotine exposure increased the risk of developing cardiovascular disease later in life. Cigarette smoking is a major risk factor for cardiovascular morbidity and mortality and is considered to be the leading preventable cause of death in the world. In the current investigation,we proved the hypothesis that prenatal nicotine treatment induces inflammatory cytokines and protooncogenes that are being used as biomarkers for the diagnosis of cardiac dysfunction onset in offspring. Materials and Methods: Female rats during pregnancy were exposed to any nicotine (6 mg/kg/day) or saline (control) using the implanted mini-osmotic pumps. After seven days of parturition, body weight, level of protein carbonyls and anti-oxidant enzymes were determined in litters. Also, the expression of cardiac hypertrophic genes and inflammatory cytokines were analyzed. Further, to delineate the role of micro RNAs, the expression of microRNA, miR-21 and miR-124 were also studied. Results: The study demonstrated that there is a substantial reduction in the levels of antioxidant enzymes in the heart tissues of pups exposed to nicotine compared to control. Moreover, on exposure to nicotine, there was a strong up-trend in the mRNA expression of c-fos, c-myc, c-jun and alpha-skeletal actin 3.4, 2.7, 4.0 and 3.5-folds respectively, was found in the heart tissue of nicotine-exposed pups. Alternatively, the indicators of inflammatory cytokines CXCR4, IL-6, IL-8, IL-16, MCP-1 were considerably improved in the nicotine-exposed which compared to control groups. Interestingly, the levels of testing micro RNAs, miR-27, -724, elicited a 2.5-fold and 4.2-fold increase in the nicotine group. Conclusion: The results of the study demonstrate that in utero exposure of nicotine induces specific changes in cardiac-related signaling mechanism to suggest that there is an increasing danger of the formation of cardiovascular illnesses like hypertension in later life.