RESEARCH ARTICLE Thymoquinone attenuates cyclophosphamide-induced pulmonary injury in rats Ghada M. Suddek • Nora A. Ashry • Nariman M. Gameil Received: 31 October 2012 / Accepted: 14 November 2012 Ó Springer Basel 2012 Abstract Objective Antioxidant therapy may be useful in diseases with impaired oxidant–antioxidant balance. This study was designed to examine the effects of thymoquinone (TQ), an anti-inflammatory, antioxidant agent against cyclophos- phamide (CP)-induced pulmonary oxidative damage. Materials and methods Male Sprague-Dawley rats were categorized into four groups. Group I was control. Group II received TQ (100 mg/kg/day, p.o.) for 14 consecutive days. Group III was injected once with CP (150 mg/kg, i.p.). Group IV received TQ for 7 consecutive days, before and after CP injection. The parameters of study were tissue oxidant/antioxidant biomarkers and histological changes in rat lungs. Results A single intraperitoneal injection of CP markedly altered the levels of several biomarkers in lung homoge- nates. Significant increases in the content of lipid peroxides in lung were seen that paralleled the decreased levels of reduced glutathione. Cyclophosphamide increased the level of serum biomarkers: total protein, lactate dehydrogenase, and tumor necrosis factor-alpha (TNF-a). Treatment of rats with TQ 7 days before and after cyclophosphamide injec- tion significantly attenuated the alterations in lung and serum biomarkers associated with inflammatory reactions, with less lipid peroxidation and restoration of antioxidants. Moreover, TQ attenuated the secretion of pro-inflammatory cytokine, TNF-a in rat serum. In addition, TQ effectively alleviated CP-induced histopathological changes in lung tissue. Discussion and conclusion Our results suggest that TQ produces a protective mechanism against CP-induced pul- monary damage and suggest a role of oxidative stress and inflammation in the pathogenesis. Keywords Cyclophosphamide Á Thymoquinone Á Antioxidant Á Anti-inflammatory Á Tumor necrosis factor-a Á Lung Á Rats Introduction Cyclophosphamide (CP) is a widely prescribed anticancer drug that has been widely used in the acute treatment of various neoplastic diseases. Its cytotoxic effects are due to chemically reactive metabolites that alkylate DNA and protein, producing cross links (Hales 1982). The injury of normal tissues is the major limitation of using CP, which gives rise to numerous side effects (Fraiser et al. 1991; Bukowski 1996). It has been reported that oxidative stress- mediated disruption of redox balance after CP exposure generates biochemical and physiological disturbances (Das et al. 2002; Ghosh et al. 2002). Lack of detoxifying enzymes, aldehyde oxidase, and aldehyde dehydrogenase, in the lungs is a cause of selective cyclophosphamide tox- icity to lung tissue. Cyclophosphamide is well known to cause various histopathologic patterns of lung injury (Kim et al. 2012). Several classes of antioxidant dietary com- pounds have been suggested to have health benefits. The evidence shows that the consumption of these products leads to decreases in various proinflammatory and/or oxi- dative stress biomarkers (Vouldoukis et al. 2004). Thymoquinone (TQ) is the most abundant compound found in Nigella sativa L. seeds. Their beneficial effects are related to antioxidant, anti-infective, antitumor, and anti- G. M. Suddek (&) Á N. A. Ashry Á N. M. Gameil Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt e-mail: ghmsuddek@yahoo.com Inflammopharmacol DOI 10.1007/s10787-012-0160-6 Inflammopharmacology 123