Resolvin D1 protects against cadmium chloride-induced memory loss and hippocampal damage in rats: A comparison with docosahexaenoic acid

Abstract

Background: Intoxication with cadmium (Cd) ions leads to hippocampal damage and cognitive impairment. However, omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert neuroprotective effects in different animal models of neurodegeneration.

Purpose: This study compared the neuroprotective effect of the n-3 PUFA, docosahexaenoic acid (DHA), and its downstream metabolite, resolvin D1 (RVD1), on hippocampal damage and memory deficits in cadmium chloride (CdCl₂)-treated rats.

Research design: Control or CdCl₂ (0.5 mg/kg)-treated rats were subdivided into three groups (n = 18/each) and treated for 6 weeks as follows: (1) fed control diet, (2) fed DHA-rich diets (0.7 g/100 g), or (3) treated with RVD1 (0.2 μg/kg, i.p).

Results: Treatment with a DHA-rich diet or RVD1 significantly increased the levels of docosahexaenoic acid and RVD1, respectively, in the hippocampal of CdCl₂-treated rats without affecting the reduction in the expression of the 15-lipooxygenase-1 (ALOX15). These effects were associated with improvements in rats' memory function and hippocampal structure, as well as a redction in the hippocampal levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear localization of the nuclear factor-kappa beta p65 (NF-κB p65), and expression of cleaved caspase-3. Concomitantly, hippocampi of both groups of rats showed significantly higher levels of Bcl-2, superoxide dismutase (SOD), and glutathione (GSH), as well as enhanced nuclear levels of the nuclear factor erythroid 2-related factor 2 (Nrf-2). The effects of RVD1 on all these markers in the CdCl₂-induced rats were more profound than those of DHA. Also, the increase in the nuclear protein levels of Nrf-2 and the decrease in the levels of Bax and nuclear protein levels of NF-κB p65 were only seen in the hippocampal of CdCl₂ + RVD1-treated rats.

Conclusion: RVD1 is more powerful than DHA in preventing CdCl₂-induced memory loss and hippocampal damage in rats.

Keywords: Cadmium; Docosahexaenoic acid; NF-kB; Nrf2; hippocampus; memory; resolvin D1.