Protective Effect of Safranal, a Constituent of Crocus sativus, on Quinolinic Acid-induced Oxidative Damage in Rat Hippocampus

Abstract

Objective(s): Quinolinic acid (QA)-mediated excitotoxicity has been widely used as a model for studying neurodegenerative disorders. Recent studies suggested that saffron (Crocus sativus) or its active metabolite, i.e. safranal, exerts pharmacological actions on central nervous system including anxiolytic, anticonvulsant, and neuroprotective properties. The present study aimed to investigate the effect safranal pretreatment on QA-induced oxidative damage in rat hippocampus.

Materials and methods: Under anesthesia, a guide cannula was stereotaxically inserted into left ventral hippocampus of rats. The rats were then given either saline or safranal (72.75, 145.5, and 291 mg/kg, IP) 30 min before administration of QA (300 nmol, intrahippocampal injection). The markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, as an index of lipid preoxidation), total sulfhydryl groups, antioxidant capacity of hippocampus (using FRAP assay), and oxidative DNA damage (%tail DNA, using comet assay) were measured in hippocampus.

Results: The QA induced a significant increase in TBARS levels and %tail DNA and remarkable decrease in antioxidant power (FRAP value) and total sulfhydryl content of hippocampus, in comparison with control animals. Systemic administration of safranal (291 mg/kg, IP), effectively and dose-dependently decreased the QA-induced lipid peroxidation (P<0.001) and oxidative DNA damage (P<0.001). Safranal also prevented the decrease of hippocampal thiol redox and antioxidant status (P<0.001) produced by QA.

Conclusion: Safranal have protective effects on different markers of oxidative damage in hippocampal tissue following QA administration. Our findings might raise a possibility of potential therapeutic application of safranal for preventing and treating neurodegenerative disorders such as Alzheimer's disease.

Keywords: Crocus sativus; Hippocampus; Neurodegenerative disorders; Oxidative stress; Quinolinic acid; Safranal.

Figure 1

Photograph representing the microinjection site of quinolinic acid into the ventral hippocampus (black arrow)

Figure 2

Effect of safranal on malondialdehyde (MDA) level of hippocampus homogenate samples following microinjection of quinolinic acid (QA, 300 nmol) into rat hippocampus. Values are mean±SEM (n=8). ^**P<0.01, ^***P<0.001 as compared with QA-treated animals; ^###P<0.001 as compared with saline-treated animals (One-way ANOVA followed by Tukey-Kramer test)

Figure 3

Effect of safranal on antioxidant power (FRAP value) of hippocampus homogenate samples following microinjection of quinolinic acid (QA, 300 nmol) into rat hippocampus. Values are mean±SEM (n=8). ^*P<0.01, ^*** P<0.001 as compared with QA-treated animals; ^###P<0.001 as compared with saline-treated animals (One-way ANOVA followed by Tukey-Kramer test)

Figure 4

Effect of safranal on total thiol concentration of hippocampus homogenate samples following microinjection of quinolinic acid (QA, 300 nmol) into rat hippocampus. Values are mean±SEM (n=8). ^*** P<0.001 as compared with QA-treated animals; ^### P<0.001 as compared with saline-treated animals (One-way ANOVA followed by Tukey-Kramer test)

Figure 5

Effect of safranal on DNA damage (percent of DNA in the comet tail, %tail DNA) following microinjection of quinolinic acid (QA, 300 nmol) into rat hippocampus. Values are mean±SEM (n=8). ^**P<0.01, ^***P<0.001 as compared with QA-treated animals; ^### P<0.001 as compared with saline-treated animals (One-way ANOVA followed by Tukey-Kramer test)