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Abstract Formaldehyde (FA) is a simplest aldehyde, it is a highly water soluble compound which can rapidly diffuse into many tissues . Due to its high chemical reactivity, the exposure to FA elicits pulmonary cell recruitment and increases microvascular leakage in the upper airways of animals , and increase the production of reactive oxygen species (ROS) and inflammation. The present study aimed to elucidate the protective role of lycopene (lyco.) , grape seed extract (GES) either individually or in combination in mitigating the oxidative stress, inflammatory and apoptotic insults on lung tissue induced by formaldehyde (FA) inhalation in experimental rat model. A total numberof 90 albino rats were used in current study. The animals were classified into nine experimental groups (10 rats /groups) . -The firstGroup: served as negative control group - The second group:rats were exposed to 10 ppm FA for (6 h / day, 5 days/week) for 8 weeks (FA 10 ppm). - The third group: rats wereexposed to 20 ppm FA for (6h / day, 5days/week) for 8 weeks (FA 20 ppm ) - The fourth group:rats wereorally administeredwith lyco in a dose of (10 mg/ kg/5day/ week for 8 weeks) prior exposure to 10 ppm FA by inhalation for (6 h / day , 5days /week) for 8 weeks (FA10PPm+ Lyco.) - The fifth group : rats were orally administered with lyco in a dose of (10 mg/ kg/5day/ week for 8 weeks) prior exposure to 20 ppm FA by inhalation for (6 h / day , 5days /week) for 8 weeks (FA 20PPm+ Lyco.) . - The sixth group : was orally administered with GSE in a dose of (150 mg/ kg/5day/ week for 8 weeks) prior exposure to 10 ppm FA by inhalation for (6 h / day , 5days /week) for 8 weeks (FA10PPm+GSE) - The seventh group : rats wereorally administered with GSE in a dose of (150 mg/ kg/5day/ week for 8 weeks) prior exposure to 20 ppm FA by inhalation for (6 h / day , 5days /week) for 8 weeks .(FA20PPm+GSE). - The eighth group:rats were orally administered with Lyco in a dose of (10 mg/ kg/day) and GSE in a dose of (150 mg/ kg/day) prior exposure to 10 ppm FA by inhalation for (6 h / day , 5days /week) for 8 weeks (FA10PPm + Lyco. + GSE). - The ninth group:rats were orally administered with Lyco. in a dose of (10 mg/ kg/day) and GSE in a dose of (150 mg/ kg/day) prior exposure to 20 ppm FA by inhalation for (6 h / day , 5days /week) for 8 weeks. (FA20PPm +Lyco+ GSE). The therapeutic potential of lycopene , grape seed extracteither individually or in combination in ameliorating the oxidative damage , inflammatory and apoptotic insults on lung tissue induced by formaldehyde (FA) inhalation in rats was evaluated . This was achieved by assessing relevant biomarkers including ; oxidative stress biomarkers [hydrogen peroxide (H2O2), nitric oxide (NO) and malondialdehyde (MDA)], antioxidant status [ glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)] in lung homogenate using spectrophotometric methods, apoptotic markers [ p53 and B cell lymphoma 2 (Bcl-2)]using ELISA technique and inflammatory markers [ IL-6 ,IL-8 and IL-10 ] in blood serum using ELISA technique.Additionally, Histopathological investigation of the lung tissue was a carried out in all groups . The obtained results were as follows: 1- The present results revealed that exposure to FA either low dose (10ppm ) and high dose (20ppm) resulted in significant elevation in lung oxidants NO, H2O2 and MDA levels accompanied with significant depletion in lung antioxidant SOD, CAT as well as GSHpxenzymes activities levels. Moreover, exposure to FA significantly increased the levels of lung P53, IL -6 and IL-8, while, significant depletion in lung Bcl-2 and serum IL-10 were recorded. 2- Treatment with lycopene and / or grape seed extract caused significant decrease inlung oxidants NO, H2O2 and MDA levels accompanied with significant increase in levels of lung antioxidant SOD, CAT as well as GSH-Px activities . Moreover, levels of lung P53 , IL -6 and IL-8 were significantly decreased,while,significant increase in lung Bcl-2 and serum IL-10 were evoked. 3- Histopathological investigation of lung tissue of rats in groups challenged to formaldehyde 10ppm and 20ppm showed peribronchiolarlymphoid hyperplasia associated with sever congestion in the blood vessels as well as peribronchoilar inflammatory cells infiltration and alveolar collapse and emphysema. 4-Histopathological examination of lung tissue of treated groups revealed significant protection against formaldehyde (FA) inhalation as indicated by improvement in the biochemical parameters. |