The present study was designed to determine the renoprotective and hepatoprotective effect of lidocaine in septic rats through the Toll‑like receptor 4 (TLR4) signaling pathway. Adult male Sprague‑Dawley rats were randomly divided into the following three groups: control, sepsis model and 10% lidocaine. A model of sepsis was established by injection of lipopolysaccharide (LPS; 5 mg/kg) into the intraperitoneal cavity of rats. The same volume of saline was injected intraperitoneally into rats of the control group instead of LPS. Light microscopy was used to observe structural changes of the hepatic and nephridial tissues. qPCR was used to measure TLR4 mRNA expression levels and the protein expression was detected by flow cytometry. Western blotting was used to measure myocardial nuclear factor κB (NF‑κB) protein levels and ELISA was used to measure the levels of interleukin‑6 (IL‑6) in hepatic and nephridial tissues. The results demonstrated that 10% lidocaine treatment markedly decreased hepatic and nephridial injury in septic rats and inhibited the expression levels of TLR4, NF‑κB and IL‑6, which were upregulated in the sepsis model. In addition, the results indicated that lidocaine protects against renal and hepatic dysfunction in septic rats, which may be mediated by the downregulation of TLR4 and associated signaling molecules and inhibition of the inflammatory response.

2,6-diisopropylphenol (propofol) is a commonly used intravenous anesthetic drug, which has been reported to serve an antitumor role in human cancers. The current study aimed to assess the effects of propofol on the biological behaviors of human bladder cancer cells and to elucidate its potential molecular mechanism. The results of MTT, wound healing and Matrigel invasion assays demonstrated that propofol significantly inhibited the viability, migration and invasion of bladder cancer T24 cells in vitro. Reverse transcription-quantitative PCR and western blotting revealed that propofol decreased the expression levels of microRNA (miR)-10b and increased the expression levels of homeobox D10 (HOXD10) in T24 cells. Luciferase reporter assay revealed that HOXD10 was a direct target of miR-10b in T24 cells. T24 cells transfected with a miR-10b mimic significantly reduced the mRNA and protein expression levels of HOXD10. In addition, overexpression of miR-10b partly reversed the inhibitory effect of propofol on T24 cell viability, migration and invasion induced by upregulation of HOXD10. In summary, the present study focused on the role of propofol in the treatment of bladder cancer and demonstrated that propofol may serve a tumor-suppressive role and control cell viability, migration and invasion of T24 cells by targeting the miR-10b/HOXD10 signaling pathway, which indicated that propofol may be used as an effective therapeutic drug for the treatment of bladder cancer.

Ischemia‑reperfusion (I/R) injury has a major impact on renal dysfunction during transplantation. The present study investigated the role of lutein against I/R injury‑induced oxidative stress in rat kidneys. Biochemical analysis and oxidative stress parameters demonstrated that lutein protected the rat kidney significantly from I/R injury. Pretreatment with lutein significantly increased the total antioxidant capacity with a concomitant decline in the total oxidant status. Rats with I/R injury showed a significant increase in oxidative stress. The results revealed significant increases in the levels of lipid peroxidation and protein carbonyl content with concomitant decreases in enzymic and non‑enzymic antioxidants. The activity of these enzymes was reversed and demonstrated a significant increase following lutein pre‑treatment compared with the rats subjected to I/R injury alone. Furthermore, lutein protected the renal tissue from I/R injury by maintaining normal kidney architecture and led to a reduction in the levels of the renal markers urea and creatinine in the serum. These results demonstrated clear evidence that lutein offered a significant protective effect against I/R injury by enhancing antioxidant defense mechanisms.

The present investigation evaluated the effect of inhibiting the P2Y12 gene on anaesthetic-induced neuronal injury in a rat model. Neuronal injury was induced by exposing the animals for 6 h to 30% oxygen containing 0.75% isoflurane and 1.2 mg/kg prasugrel (a P2Y12 inhibitor) p.o. for 14 days. Cognitive function was determined by the Morris water maze, and the neurological severity score was determined. Enzyme-linked immunosorbent assay was used to estimate the level of oxidative stress and mediators of inflammation in brain tissues of isoflurane-induced neuronal injury rats. Apoptosis of neuronal cells was estimated by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot assays. Real time-polymerase chain reaction was performed to estimate the expression levels of several proteins. The data revealed that inhibiting the P2Y12 gene ameliorated changes in the modified neurological severity score and cognitive function in neuronal injury rats. Moreover the levels of proinflammatory mediators, oxidative stress, and cyclic AMP, and the number of TUNEL-positive cells, decreased significantly (p < 0.01) in the prasugrel-treated group compared to the negative control group. In addition, apoptosis of neuronal cells decreased in the prasugrel-treated group, as it ameliorated expression of the PI3K, Bcl-2, Bad, and Akt proteins in the isoflurane-induced neuronal injury rats. Expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) proteins was enhanced, whereas the Toll-like receptor-4 (TLR-4) and nuclear factor κB (NF-κB) proteins decreased in the brain tissues of the prasugrel-treated group compared to the negative control group of rats. These results suggest that inhibiting the P2YR12 gene protects against neuronal injury in isoflurane-induced neuronal injury rats. Inhibiting the P2YR12 gene ameliorated neuronal apoptosis by regulating the BDNF/TLR-4/TNF-α pathway.