Numerous agents have been reported to prevent cell lysis. However, little information is available concerning the ability of cytoprotectants to promote the return of physiological functions. The goal of this study was to determine whether a diverse group of cytoprotectants prevent cell lysis and promote the recovery of respiration and ion transport following anoxia (60 min)/reoxygenation (60 min) in rabbit renal proximal tubule (RPT) suspensions. Cell lysis (LDH release) was determined immediately following the anoxic and reoxygenation periods. Mitochondrial function (basal respiration) and active Na+ transport (ouabain-sensitive respiration) was determined after the reoxygenation period. LDH release increased to 75 +/- 11% after the anoxic period and did not increase further during the reoxygenation period. LDH release in controls was 6 +/- 1% and did not vary over time. Glycine (2 mM), strychnine (1 mM), nifedipine (100 microM) and niflumic acid (100 microM) added immediately prior to the anoxic period completely blocked LDH release. All cytoprotectants increased basal respiration from 39 +/- 7% of controls in the anoxic samples to 65-77% of controls. Glycine, strychnine and nifedipine increased ouabain-sensitive respiration from 10 +/- 3% of controls in anoxic samples to 51-77% of control. Niflumic acid did not increase ouabain-sensitive respiration. These results demonstrate that glycine, strychnine and nifedipine are "true' cytoprotectants preventing both cell lysis and promoting the recovery of mitochondrial function and ion transport after an anoxic insult.