Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1β (TGF-1β) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1β levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Methotrexate (Mtx) is an effective chemotherapeutic agent used in various cancer treatments. Gastrointestinal toxicity is the drug’s major limiting factor, arising mainly from oxidative damage. It ...

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1β and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1β, lung GSH-Px and histologic outcome.

Nitric oxide (NO) and peroxynitrite (OONO-) are implicated in the pathophysiology of renal ischemia/reperfusion (I/R). The aim of this study was to investigate and compare the efficiency of S-methylisothiourea (SMT), an iNOS inhibitor, and mercaptoethylguanidine (MEG), a scavenger of peroxynitrite, on renal dysfunction and injury induced by I/R of rat kidney. Thirty-two male Sprague-Dawley rats were divided into four groups: sham-operated, I/R, I/R+SMT, and I/R+MEG. Rats were given SMT (10 mg/kg i.p.) or MEG (10 mg/kg i.p.) 6 h prior to I/R and at the beginning of reperfusion. All rats except sham-operated underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehide, protein carbonyl content, and nitrite/nitrate level (NO(x)) were determined in the renal tissue. Serum creatinine (S(Cr)), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. SMT and MEG significantly reduced the I/R-induced increases in S(Cr), BUN, and AST. Both SMT and MEG attenuated the tissue NO(x) levels, indicating reduced NO production. In addition, SMT and MEG markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Interestingly, MEG exerted a greater renoprotective effect than SMT. These data support the finding that iNOS and peroxynitrite are involved in the renal I/R injury, and suggest that a scavenger of peroxynitrite might be more effective than iNOS inhibitors as a therapeutic intervention.