Effects of Topically Applied Contractubex® on Epidural Fibrosis and Axonal Regeneration in Injured Rat Sciatic Nerve.

AIM: To investigate the effects of Contractubex® (Cx) on peripheral nerve regeneration and scar formation. MATERIAL AND METHODS: A surgical procedure involving sciatic nerve incision in 24 adult male Sprague-Dawley rats followed by epineural suturing was performed. In weeks 4 and 12 following surgery, macroscopic, histological, functional, and electromyographic examinations of the sciatic nerve were conducted. RESULTS: No significant difference was found between the Cx group and the control group in terms of sciatic function index (SFI) and distal latency results at week 4 (p > 0.05). However, significant improvements in the Cx group were observed in SFI amplitudes and nerve action potentials at week 12 (p < 0.001 and p < 0.001, respectively). Significant improvements were found in the amplitudes of nerve action potentials in the treatment group after weeks 4 and 12 (p < 0.05 and p < 0.001, respectively). Macroscopically and histopathologically, epidural fibrosis decreased (p < 0.05 and p < 0.001, respectively). For both measurement times, the treatment group had significantly higher numbers of axons (week 4, p < 0.05; week 12, p < 0.001), and the treatment group had better results regarding its axon area (weeks 4 and 12, p < 0.001) and myelin thickness (weeks 4 and 12, p < 0.05). CONCLUSION: Cx, which is applied topically in peripheral nerve injury, affects axonal regeneration and axonal maturation positively and reduces the functional loss.

Effects of combined administration of doxorubicin and chloroquine on lung pathology in mice with solid Ehrlich ascites carcinoma.

Combined use of a chemotherapeutic agent and an autophagy inhibitor is a novel cancer treatment strategy. We investigated the effects of chloroquine (CQ) on lung pathology caused by both solid Ehrlich ascites carcinoma (EAC) and doxorubicin (DXR). A control group and eight experimental groups of adult female mice were inoculated subcutaneously with 2.5 × 106 EAC cells. DXR (1.5 mg/kg and 3 mg/kg) and CQ (25 mg/kg and 50 mg/kg) alone or in combination were injected intraperitoneally on days 2, 7 and 12 following inoculation with EAC cells. Lung tissue samples were examined using immunohistochemistry (IHC) for endothelial (eNOS), inducible nitric oxide synthase (iNOS) and neutrophil gelatinase-associated lipocalin (NGAL). Serum catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using ELISA. We found decreased levels of iNOS and eNOS in the groups that received 1.5 mg/kg DXR alone and in combination with 25 mg/kg and 50 mg/kg CQ. Combined administration of DXR and CQ partially prevented disruption of alveolar structure. Levels of antioxidant enzymes and MDA were lower in all treated groups; the greatest reduction was observed in mice that received the combination of 25 mg/kg CQ + 1.5 mg/kg DXR. Levels of NGAL were elevated in all treated groups. We found that CQ ameliorated both EAC and DOX induced lung pathology in female mice with solid EAC by reducing oxidative stress.

Chloroquine Used in Combination with Chemotherapy Synergistically Suppresses Growth and Angiogenesis In Vitro and In Vivo.

BACKGROUND: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy. MATERIALS AND METHODS: The cytotoxic effect of doxorubicin (0.1-1 µM), chloroquine (0.25-32 µM) and their combination were investigated by employing ATP assay in human umbilical vein endothelial cells (HUVECs). The effect of doxorubicin and chloroquine combination was also measured using tube formation assay on Matrigel. The anti-angiogenic activities of doxorubicin (2.5 µg/pellet) and chloroquine (15 µg/pellet), their combination, and standards (50 µg/pellet) were tested in vivo using the chick embryo chorioallantoic membrane (CAM) assay. RESULTS: The combination of doxorubicin and chloroquine significantly had a stronger anti-angiogenic effect than the positive control (±)-thalidomide and doxorubicin alone in the CAM assay and in vitro tube-formation assay. CONCLUSION: Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.