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Propofol is an anesthetic agent moderating GABA receptors in the nervous system. A number of studies have demonstrated that propofol exerts a negative effect on neural stem cell development in the neonatal mouse hippocampus. However, to the best of our knowledge, there is no study available to date illustrating whether neonatal exposure to propofol affects Leydig stem/progenitor cell development for normal male reproductive development and functions, and the regulatory mechanism remains elusive. In the present study, TM3 cells, a mouse Leydig stem/progenitor cell line, was treated with propofol. The data illustrated that propofol significantly reduced TM3 cell viability. TM3 subG1 phase cell numbers were significantly increased by propofol assayed by flow cytometric analysis. Annexin V/PI double staining assay of the TM3 Leydig cells also demonstrated that propofol increased TM3 cell apoptosis. In addition, cleaved caspase‑8, ‑9 and ‑3 and/or poly(ADP‑ribose) polymerase (PARP) were significantly activated by propofol in the TM3 cells. Furthermore, the expression levels of phospho‑JNK, phospho‑ERK1/2 and phospho‑p38 were activated by propofol in the TM3 cells, indicating that propofol induced apoptosis through the mitogen‑activated protein kinase (MAPK) pathway. Additionally, propofol diminished the phosphorylation of Akt to increase the apoptosis of TM3 cells. On the whole, the findings of the present study demonstrate that propofol induces TM3 cell apoptosis by activating caspases and MAPK pathways, as well as by inhibiting the Akt pathway in TM3 cells. These findings illustrate that propofol affects the viability of Leydig stem/progenitor cells possibly related to the development of the male reproductive system.

In the western world, there is an increasing trend of occurrence in testicular cancer. Treatment of malignant testicular cancer is primarily combined surgery with various chemical drugs. Propofol has been frequently used as an anesthetic and sedative induction agent, which could modulate different γ‑aminobutyric acid receptors in the central nervous system. Studies demonstrated that propofol activates endoplasmic reticulum stress to induce apoptosis in lung cancer. However, it remains elusive whether propofol regulates caspase and/or mitogen‑activated protein kinase (MAPK) pathways to induce apoptosis in Leydig tumor cells. In the present study, MA‑10 mouse Leydig tumor cells were treated with propofol, and possible signal pathways associated with apoptosis were investigated. Results demonstrated that increasing dosage of propofol (300‑600 µM) for 24 h significantly decreased cell viability in MA‑10 cells (P<0.05). In flow cytometry analysis, the amount of sub‑G1 phase cell numbers in MA‑10 cells was significantly increased by propofol (P<0.05). Additionally, Annexin V/propidium iodide double staining further confirmed that propofol could induce MA‑10 cell apoptosis. Furthermore, cleaved caspase‑8, ‑9 and ‑3, and/or poly(ADP‑ribose) polymerase were significantly activated following treatment of propofol in MA‑10 cells. In addition, c‑Jun N‑terminal kinase, extracellular signal‑regulated kinase 1/2, and p38 were significantly activated by propofol in MA‑10 cells (P<0.05), indicating that propofol may induce apoptosis through the MAPK pathway. Additionally, propofol diminished the phosphorylation of Akt to activate apoptosis in MA‑10 cells. In conclusion, propofol may induce MA‑10 cell apoptosis by activating caspase and MAPK pathways, and inhibiting the Akt pathway in MA‑10 cells, demonstrating that propofol may be a potential anticancer agent against Leydig cell cancer.

Background: Propofol has several properties beneficial to intracranial operation such as reduction in cerebral metabolic rate and cerebral blood flow (CBF) in a dose-dependent manner while leaving autoregulation intact. Several studies have demonstrated that the responsiveness of CBF to changes in arterial carbon dioxide tension (PaCO2) is maintained during propofol anesthesia in both humans and animals. These studies showed a significant difference in the CBF-CO2 reactivity slope between awake and propofol anaesthetized groups, but no comparison with different doses of propofol was made. To determine the dose effect of propofol on cerebrovascular CO2 reactivity, we used laser Doppler flowmetry (LDF) to detect the changes of CBF during propofol anesthesia., Methods: Ten rabbits were studied using LDF on the parietal cortex. After surgical preparation, anesthesia was maintained with 66% N2O in O2, morphine 10 mg/kg and pancuronium. Three experimental conditions were studied sequentially with intravenous administration of the following drugs: (1) normal saline (control), (2) propofol 20 mg/kg/h i.v., (3) propofol 40 mg/kg/h i.v. Mean arterial pressure, rectal temperature and hematocrit were kept constant. The arterial carbon dioxide tension (PaCO2) was adjusted to three levels during each condition: 20-25 mmHg (hypocapnia), 35-40 mmHg (normocapnia) and 45-50 mmHg (hypercapnia). CBF was measured continuously and recorded after the target PaCO2 had been reached., Results: There were no differences among all conditions in mean arterial pressure and heart rate. The changes of CBF as PaCO2 increased at the three different CO2 levels during each of the conditions were significantly different. The slope of CBF-CO2 reactivity among three different propofol doses was not significantly different., Conclusions: These data indicate that cerebral vasomotor responsiveness to CO2 during propofol anesthesia is preserved and that the slope of CBF-CO2 reactivity is independent of propofol doses as mean arterial blood pressure is maintained.