Effects of Lycopene in Hyperoxia-Induced Lung Injury in Newborn Rats
Abstract
Abstract. The aim of this study was to evaluate the therapeutic effect of lycopene on a hyperoxia-induced lung injury model in rat pups. Full-term rat pups were included in the study 12–24 h after delivery. The pups were separated into 4 groups: normoxia control (NC), hyperoxia control (HC), hyperoxia + lycopene (HL), and normoxia lycopene (NL). The normoxia groups were housed in ambient air, and the hyperoxia groups in > 85% O2. HL and NL groups received 50 mg lycopene in oil/kg body weight/day delivered intraperitoneally (i.p.), the other groups received oil alone. On day 11, the rat pups were sacrificed and their lungs removed. Statistically significant injury was observed in all histological parameters measured (MLI, proliferating cell nuclear antigen (PCNA), and apoptosis) in the HC group (HC vs NC, p = 0.001). This injury could not be reversed with lycopene treatment (HC vs HL, 0.05; NC vs HL, p = 0.001). With hyperoxia, statistically significant decreases were observed in biochemical parameters in terms of SOD, MDA, and IL-6 values (HC vs NC: SOD, p = 0.02; MDA, p = 0.043; IL-6, p = 0.001). The use of lycopene did not provide any improvement in these values (HC vs HL, p > 0.05). Hyperoxia or lycopene had no effect on IL-1β and GPx (p > 0.05). When comparing NC and NL groups, negative effects were observed in the group given lycopene in terms of MLI, PCNA, apoptosis, and IL-6 (all parameters, p = 0.001). We observed that 50 mg lycopene in oil/kg body weight/day given via i.p. had no curative effect on the hyperoxia-induced lung injury in newborn rats and may even induce adverse effects.
References
1 . (2000) I: primary outcomes. Pediatrics. 105, 295–310.
2 (1988) Effects of dexamethasone and indomethacin on elastase, alpha 1-proteinase inhibitor, and fibronectin in bronchoalveolar lavage fluid from neonates. J. Pediatr. 113, 727–731.
3 (2003) Bronchopulmonary dysplasia-oxidative stress and antioxidants. Semin. Neonatol. 8, 39–49.
4 (2001) Oxidative stress and increased type-IV collagenase levels in bronchoalveolar lavage fluid from newborn babies. Pediatr. Res. 50, 29–33.
5 (1967) Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N. Engl. J. Med. 276, 357–368.
6 (2001) Bronchopulmonary dysplasia. Am. J. Respir. Crit. Care. Med. 163, 1723–1729.
7 (1998) Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1993 through December 1994. Am. J. Obstet. Gynecol. 179, 1632–1639.
8 (2001) Oxidants and antioxidants in atherosclerosis. Curr. Opin. Lipidol. 12, 411–418.
9 (2001) Testosterone and food restriction modulate hepatic lycopene isomer concentrations in male F344 rats. J. Nutr. 131, 1746–1752.
10 (1992) Protection by beta-carotene and related compounds against oxygen-mediated cytotoxicity and genotoxicity: implications for carcinogenesis and anticarcinogenesis. Free Radic. Biol. Med. 13, 407–433.
11 (1998) Lycopene: chemistry, biology, and implications for human health and disease. Nutr. Rev. 56, 35–51.
12 (2001) Lycopene content of tomato products: Its stability, bioavailability and in vivo antioxidant properties. J. Med. Food. 4, 9–15.
13 (1989) Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch. Biochem. Biophys. 274, 532–538.
14 (1991) The singlet oxygen and carotenoid interaction. J. Photochem. Photobiol. B. 11, 41–47. Erratum in: J. Photochem. Photobiol. B. 1993. 17, 89.
15 (2008) Multitargeted therapy of cancer by lycopene. Cancer Lett. 269, 339–351.
16 (1991) Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/1077/2 cells: relationship to their cancer chemo preventative action. Carcinogenesis. 12, 2109–2114.
17 (2000) Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat. Cancer Lett. 154, 201–210.
18 (2012) Effects of lycopene on the model of oleic acid-induced acute lung injury. Tuberk. Toraks. 60, 101–107.
19 (2009) Anti-inflammatory effect of lycopene on carrageenan-induced paw oedema and hepatic ischaemia-reperfusion in the rat. Br. J. Nutr. 102, 126–133.
20 (1962) Quantitative methods in the study of pulmonary pathology. Thorax. 17, 320–328.
21 (2007) Azithromycin protects against hyperoxic lung injury in neonatal rats. J. Investig. Med. 55, 299–305.
22 (2013) Timing of umbilical cord blood derived mesenchymal stem cells transplantation determines therapeutic efficacy in the neonatal hyperoxic lung injury. PLoS One. 8, e52419.
23 (2006) Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia. Am. J. Physiol. Lung. Cell. Mol. Physiol. 291, L1068–L1078.
24 (2011) Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells. Am. J. Physiol. Lung. Cell. Mol. Physiol. 301, L187–L196.
25 (2005) Nuclear dynamics of PCNA in DNA replication and repair. Mol. Cell. Biol. 25, 9350–9359.
26 (2008) Twenty-eight-day oral toxicity study of lycopene from recombinant Escherichia coli in rats. Regul. Toxicol. Pharmacol. 52, 163–168.
27 (1998) Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutr. Cancer. 31, 199–203.
28 (1960) Lycopenemia: a variant of carotenemia. N. Engl. J. Med. 262, 263–269.
29 (1999) Lycopene and beta-carotene protect against oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher doses. Free Radic. Res. 30, 141–151.
30 (1999) Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Blood. 94, 2102–2111.
31 (2001) Lycopene modulates circulatory antioxidants during hamster buccal pouch carcinogenesis. Nutr. Res. 21, 1447–1453.
32 (2001) Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate. Arch. Biochem. Biophys. 396, 171–177.
33 (2014) Protective effects of melatonin therapy in model for neonatal hyperoxic lung injury. Altern. Ther. Health. Med. 20, 24–29.
34 (2011) Hydrogen-rich saline provides protection against hyperoxic lung injury. J. Surg. Res. 165, e43–e49.
35 (2012) Colchicine protects against hyperoxic lung injury in neonatal rats. Neonatology. 102, 265–269.
36 (2010) Activated protein C attenuates acute lung injury and apoptosis in a hyperoxic animal model. Shock. 33, 467–472.
37 (2010) Does hypercapnia ameliorate hyperoxia-induced lung injury in neonatal rats? Lung. 188, 235–240.