Induction of heme oxygenase-1 attenuates chemotherapy-induced pulmonary toxicity in rats: A possible link between heme oxygenase-1 and NF-κB.
A critical restriction in the use of bleomycin (BLM) is development of pulmonary fibrosis via oxidative and inflammatory mechanisms. Drugs that induce heme oxygenase-1 (HO-1) like hemin (HEM), have anti-inflammatory, antioxidant, and immunomodulatory effects. Accordingly, it is worth to test HEM against BLM-induced lung Injury. Four groups of rats were used: control group; HEM group (50 mg/kg, i.p.); BLM group (5 mg/kg, intratracheal single injection) and HEM+BLM group (HEM administered 1 day before BLM injection and continued for 14 days). At the end of experiment, lactate dehydrogenase (LDH) and NO levels were estimated in bronchoalveolar lavage fluid (BALF). Hydroxyproline (HP), myeloperoxidase (MPO), IL-6, GSH, MDA levels and SOD activity were determined in lung tissues. In addition, expression of HO-1 and NF-κB protein in lung tissues was determined using both western blot and immunohistochemical techniques. Also lung tissues were investigated histopathologically. BLM produced lung damage as indicated from the elevation in LDH and NO, perturbation in lung oxidative stress indicators, increased HP, MPO, IL-6 contents and NF-κB expression. On the other side, HEM, reduced BLM harmful effects as noticed from amelioration of biochemical markers and histopathological lesions, which is concomitant with over-expression of HO-1. Therefore, induction of HO-1 in lung by HEM may alleviate the lung damaging effects of BLM.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt / Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al Qura University, Makkah, Saudi Arabia.
Ihab Talat
IT
Abdel-Raheem
Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
Gamal Abd El-Hay
GA
Omran
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D004790:Enzyme Induction; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D016328:NF-kappa B; D001761:Bleomycin; D051547:Heme Oxygenase-1