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.

Insights into HPLC-MS/MS Analysis, Antioxidant and Cytotoxic Activity of Astragalus fruticosus against Different Types of Cancer Cell Lines.

Plants from the genus Astragalus are gaining attention for their pharmacological importance. However, the information available regarding the HPLC-MS/MS chemical profile of A. fruticosus is inadequate. In this study, we performed HPLC-MS/MS analysis using electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). We tentatively identified 11 compounds in the A. fruticosus methanolic extract, including five flavonoidal and six saponin glycosides. The extract showed moderate antioxidant activity with 21.05% reduction in DPPH UV absorption. The preliminary cytotoxic screening against seven human cancer cell lines using 100 µg/mL extract showed prominent cytotoxic potential against colorectal cancer HCT-116 with 3.368% cell viability. It also showed moderate cytotoxic potential against prostate (DU-145), ovarian (SKOV-3) and lung (A-549) cancer cell lines with cell viability of 14.25%, 16.02% and 27.24%, respectively. The IC50 of the total extract against HCT-116 and DU-145 cell lines were 7.81 µg/mL and 40.79 µg/mL, respectively. The observed cytotoxicity of the total methanolic extract from the leaves against colorectal cancer might facilitate future investigations on cytotoxic agent(s) for disease management.