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Although the nephrotoxicity of cisplatin has been well documented as a major side effect of chemotherapy, the exact mechanism by which prosurvival and apoptotic pathways interplay to determine renal pathology remains elusive. Recent studies suggested that autophagy might serve as an adaptive mechanism to promote cell survival during acute kidney injury (AKI). We have used AKI as a disease model to investigate the mechanism regulating the cytoprotective role of autophagy in cisplatin-induced tissue damage. Pharmacological inhibitors such as chloroquine were used to manipulate autophagy during AKI, and DNA damage was evaluated by using the cellular marker γH2AX. Cisplatin induced extensive DNA damage during AKI. Autophagy activation served as a survival strategy to suppress cisplatin-induced DNA damage in the pathology of AKI both in vitro and in vivo. Interestingly, in the kidney, cisplatin treatment can activate AMP-activated protein kinase (AMPK), a signaling molecule that is also critical for p53-mediated inactivation of mammalian target of rapamycin (mTOR) pathways. As a result, inhibition or knockdown of AMPK can lead to repressed autophagy in cisplatin-induced AKI, resulting in more DNA damage. Activation of AMPK regulates autophagy during cisplatin-induced AKI. Given the fact that p53 can regulate autophagy by inactivating mTOR via AMPK, our results suggest that the p53 pathway may also play a critical role in the pathogenesis of cisplatin-induced renal damage. This study may further our understanding of the physiological roles of autophagy in the pathogenesis of renal injuries, and thus may have pathological implications in the clinical setting.

No abstract

Background: Endotracheal intubation (ETI) can cause a cardiovascular response. The aim of the present study was to investigate the effect of intravenous lidocaine on the hemodynamic response to ETI during sufentanil-based induction of anaesthesia.Methods: Ninety patients aged 18-65 years were recruited, induction of anaesthesia was initiated by sufentanil, midazolam, cisatracurium, and propofol, the patients were randomized to three groups: Group L1 received 1 mg/kg -1 of lidocaine, Group L1.5 received 1.5 mg kg -1 of lidocaine, Group S received an equal volume of normal saline (NS). Lidocaine or NS was administered in a bolus 2 min before ETI. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and heart rate (HR) were recorded at four time points: before anaesthetic induction, 1 min after lidocaine administration, immediately after ETI, 5 min after ETI. The incidences of hypotension, hypertension, bradycardia, and tachycardia were also recorded. Results:The SAP, DAP, MAP, and HR at baseline were not significantly different among the three groups (P = 0.620, P = 0.575, P = 0.433, P = 0.537, respectively). Immediately after ETI, the SAP in Group L1 was significantly lower than Group S (P = 0.024), while the DAP, MAP, and HR were comparable among the three groups at the same time points (P > 0.05). There were no significant differences in the incidences of hypotension, hypertension, bradycardia and tachycardia among the three groups (P > 0.200). Conclusions:Intravenous lidocaine could attenuate the increase of blood pressure but not HR after ETI during sufentanil-based induction of anaesthesia without increased incidence of side-effects.