Cadmium (Cd) exists in the natural environment. It can accumulation in the body for a long period, leading to damaged various tissues and organs. It is also a highly toxic heavy metal. The Japanese incident of Itai disease in 1912 brought widespread attention to Cd toxicity [1]. Although many countries have taken steps to control the occurrence of Cd pollution, it continues to exist in many areas [2]. Cd pollution in the environment mainly results from the emission of waste water containing Cd from industrial production, the application of Cd containing fertilizers from agricultural production, and the ad-libitum disposal of Cd containing batteries. The Cd in the environment eventually accumulates in human and animal bodies through bioaccumulation, thus posing a serious threat to the stability of ecosystems and human health.

Direct contact, respiration, and the digestive system are the main routes through which Cd enters the body [3]. The kidney is the main metabolic organ and a key target organ for Cd poisoning [4]. When Cd poisoning occurs, liver tissue cells die due to toxicity or the body’s own protective mechanism; the Cd-metallothionein (MT) complexes in tissue cells enter blood circulation and further reach the kidney due to the filtration effect of the glomerulus, and they are reabsorbed by the body’s renal tubules [5]. Then, they constantly accumulate after enhancing the chronic toxicity of Cd [6]. Prolonged exposure to Cd can lead to malfunctioned renal Cd metabolism and excessive Cd accumulation in the kidneys, causing body calcium loss and kidney stones [7]. It can also cause renal failure and lead to death [8]. Current studies showed that the molecular mechanisms of kidney damage caused by Cd poisoning are mainly through activating oxidative stress and causing mitochondrial or endoplasmic reticulum (ER) stress, leading to cell apoptosis and calcium disorder [9].

The ER is central in the membrane system of eukaryotic cells, comprising approximately 50 % of the intracellular membrane [10]. It can be divided into rough- and light-faced ER on the basis of the number of ribosomes attached to its luminal face. ER stress is caused by either the disturbance of calcium absorption; the release function in the ER; or processes, such as protein synthesis, processing, and secretion, that produce a series of physiological responses. The ER overload response (EOR), unfolded protein response (UPR), and sterol regulatory original binding protein pathway regulatory response (SREBP) induced by cholesterol deficiency have been identified to date as the three main causes of ER stress.

Apoptosis refers to the spontaneous and orderly death of cells regulated by genes, with the aim of maintaining the stability of the in-vivo environment. ER stress can induce cell apoptosis. The three currently known pathways by which ER stress activates apoptosis are as follows [11], [12], [13]: (1) In the PERK pathway, PERK activation continues to activate downstream eIF2α, ATF4, CHOP, and other molecules. (2) IRE1 signaling upregulates Pro Bim and downregulates Bcl-2 expression by activating the associated JNK signaling pathway. (3) The Caspase family’s classical apoptotic pathway activates Caspase-12, followed by the reactivation of other caspase family members, leading to apoptosis.

Quercetin (Que), a flavonol compound with various biological activities, exists in the bark, seeds, fruits, flowers, and leaves of many plants [14]. The special co-orbital system of Que resulted in its enhanced antioxidant capacity, efficient chelation of transition metal ions, and free radical scavenging [15]. Que also has antimicrobial, glucose-lowering, anticancer, and cardiovascular protective pharmacological effects. Que is the most easily absorbed dietary flavonoid, and it does not remain in body tissues nor fluids [16].

In this study, a rat kidney Cd toxicity model was established, and Que was used to antagonize Cd toxicity. The expression of the PERK signaling pathway in the kidney provide a theoretical basis for further elucidating the role of this pathway under ER stress in Cd-induced renal cell apoptosis in rats and the intervention mechanism of Que.