Naringenin reduces cadmium-induced depression and memory deficits via the remediation of neuroinflammation, glutamate excitotoxicity, and DNA fragmentation

Abstract

Cadmium (Cd) is a heavy metal with negligible biodegradability and extended biological half-life and its use is ubiquitously increased in modern-day life. Exposure to Cd affects every biological system, including the brain and nervous system. Neurotoxicity induced by Cd exposure produces major health impacts since it exerts behavioral dysfunctions that can affect daily routine life. Because of its unavoidable use, it is necessary to search the dietary components that can combat Cd-induced neurotoxicity. Naringenin is the main flavonoid found in grapefruits and oranges, and low amounts of naringenin are found in tomatoes as well. Its antioxidant and anti-inflammatory effects have been described repeatedly. It has also been reported to reduce Cd-induced renal dysfunction and testicular toxicity. This study was conducted to evaluate the mitigating effects of naringenin in animal model of Cd-induced neurotoxicity. Cd neurotoxicity was determined by behavioral analysis in terms of depressive behavior and memory function. We found that Cd toxicity exerted depression-like behavior and memory dysfunction in rats, which was attenuated by the pre-treatment of naringenin. To determine the insight of these effects of naringenin, we identified some biomarkers affiliated with the neurotoxicity. We found increased glutamate excitotoxicity, inflammation, and increased DNA fragmentation in rat brain exposed to Cd. These biomarkers were significantly attenuated by naringenin pre-treatment, which was also reflected by reduced depression-like symptoms and improved memory performance in Cd-exposed rats treated with naringenin. Here, we suggest that consumption of naringenin can be adopted to protect brain function from Cd-induced neurotoxicity.