Protective Effects of Quercetin on Cadmium-induced Cytotoxicity in Primary Cultures of Rat

Protective Effects of Quercetin on Cadmium-induced Cytotoxicity in Primary Cultures of Rat

Proximal Tubular Cells*

WANG Lin1,?, LIN Shu Qian2,?, HE Yuan Long2, LIU Gang1, and WANG Zhen Yong1,#

【摘 要】Abstract Objective To investigate the protective effects of quercetin on cadmium-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells.

【期刊名称】生物医学与环境科学（英文版） 【年(卷),期】2013(026)004 【总页数】10

【关键词】Key words: Cadmium; Quercetin; Oxidative stress; Apoptosis; Proximal tubular cells; Primary cell culture

Methods Primary cultures of rPT cells undergoing exponential growth were incubated with 1.0 μg/mL quercetin and/or cadmium (2.5, 5.0 μmol/L), in a serum-free medium at 37 °C at different time intervals. Commercial kits were used and flow cytometric analyses were performed on rPT cell cultures to assay apoptosis and oxidative stress. Results Exposure of rPT cells to cadmium acetate (2.5, 5.0 μmol/L) induced a decrease in cell viability, caused an increase in apoptotic rate and apoptotic morphological changes. Simultaneously, elevation of intracellular reactive oxygen species, malondialdehyde and calcium

levels, depletion of mitochondrial membrane potential and intracellular glutathione, and inhibition of Na+, K+-ATPase, Ca2+-ATPase, glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were revealed during the cadmium exposure of rPT cells. However, simultaneous supplementation with 1 μg/mL quercetin protected rPT cells against cadmium-induced cytotoxicity through inhibiting apoptosis, attenuating lipid peroxidation, renewing mitochondrial function and elevating the intracellular antioxidants (non-enzymatic and enzymic) levels.

Conclusion The present study has suggested that quercetin, as a widely distributed dietary antioxidant, contributes potentially to prevent cadmium-induced cytotoxicity in rPT cells.

INTRODUCTION

admium (Cd) is known to be an occupational hazard and an environmental pollutant. Unlike complex organic pollutants, cadmium cannot be degraded by microorganisms. Instead, it accumulates in ecosystems and enters the food chain through environmental contamination of soil and water for an extremely long biological half-life. Long-term exposure to cadmium results in direct toxic effects[1]. It exerts multiorgan toxic effects in mammals and the kidney is the critical target organ for cadmium toxicity. The nephrotoxicity of cadmium has been extensively studied and widely reported in literatures. There is

growing evidence that oxidative stress via reactive oxygen species (ROS) generation and mitochondrial damage are among the fundamental molecular mechanisms of cadmium nephrotoxicity[2-4]. Moreover, apoptotic death formed in the presence of cadmium could be responsible for its toxic effects[3,5-7].

In recent years, numerous studies have been exploring the therapeutic properties of extracts from different parts of various medicinal plants. The positive effects of flavonoids on human health have been given much attention. Flavonoids are natural phenolic substances that act as antioxidants in biological systems[8]. Quercetin, one of the most abundant flavonoids, is widely distributed in fruits and vegetables like apples, onion, mulberry, potatoes, broccoli, tea, peanuts, soybeans and red wine and is a potent oxygen free radicals scavenger[8-9]. It has been shown that quercetin has highly potent antioxidant and cytoprotective effects in preventing apoptosis and oxidative damage induced by cadmium in both in vivo and in vitro studies[2,7]. In view of these considerations, quercetin was chosen to evaluate its protective effect on cadmium-induced cytotoxicity in this study.

However, concerning the protective effect of quercetin on Cd-induced nephrotoxicity, only some experiments concentrated on in vivo studies and primary cultures of tubular cells were minimally applied[2,8].Cell cultures are valuable tools for mechanistic studies at the cellular level.