Effect of quercetin on the IRE1-XBP1 apoptotic pathway in Cadmium-treated rat testes.

Background: Cadmium (Cd) is a recognized toxic metal with serious reproductive toxicity in both animals and humans, while quercetin (Que) is considered the potent antioxidant among flavonoid compounds. However, little is known about the alleviating effect of Que on Cd-induced testicular cell apoptosis. This experiment aims to investigate the alleviating effect of Que on Cd-induced testicular cell apoptosis in rats.

Methods: Twenty-four four-week-old male Sprague-Dawley rats were randomly divided into control group, Cd group, Cd + Que group and Que group. Following the assigned treatments, the testicular tissues of the rats were examined 28 days later. The levels of malondialdehyde (MDA) and reducing glutathione (GSH) in testicular tissue were measured via colorimetry, with HE (hematoxylin and eosin) and TUNEL (a TdT-UTP nick end labeling) staining employed to assess tissue damage and cell apoptosis. Total mRNA (messenger RNA) was extracted from testicular tissue using the Trizol method, and reverse transcription was followed by quantitative real-time PCR (Polymerase Chain Reaction) to measure the expression levels of relevant genes. The expression of related proteins was assessed using Western blot.

Results: The data revealed that Cd exposure led to a decrease in body weight and a significant increase in MDA and GSH content in testicular tissue. In addition, histopathological examination of the tissue revealed extensive pathological changes, and TUNEL staining showed significant cell apoptosis in the tissue. Furthermore, Cd treatment promoted the expression of relevant genes, including IRE1α (inositol-requiring kinase 1), Caspase-12, XBP1 (X box-binding protein 1), GRP78 (glucose-regulated protein 78), Bax and Caspase-3, in the IRE1-XBP1 apoptosis pathway. Meanwhile, the anti-apoptotic gene Bcl-2 was significantly decreased. However, the application of Que significantly reduced these alterations and cellular damage induced by Cd.

Conclusions: Our study suggests that Que can mitigate testicular tissue damage and cell apoptosis resulting from Cd exposure by suppressing oxidative stress and the IRE1-XBP1 pathway.