Alleviation of cadmium-induced oxidative stress by trehalose via inhibiting the Nrf2-Keap1 signaling pathway in primary rat proximal tubular cells.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tre) protects primary rat proximal tubular (rPT) cells against cadmium (Cd)-induced oxidative stress via Nrf2 antioxidant pathway. Data showed that Tre treatment inhibited Nrf2 nuclear translocation and restored the decline in Kelch-like ECH-associated protein 1 (Keap1) protein level in Cd-exposed rPT cells. Moreover, Cd-activated Nrf2 target genes, including phase II detoxifying enzymes, that is, NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1, direct antioxidant proteins, that is, glutathione peroxidase, superoxide dismutase, catalase, and glutathione biosynthesis-related proteins, that is, glutamatecysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione reductase, were all downregulated by co-treatment with Tre. Collectively, these findings demonstrate that Tre treatment alleviates Cd-induced oxidative stress in rPT cells by inhibiting the Nrf2-Keap1 signaling pathway.

Wang XY ，Wang ZY ，Zhu YS ，Zhu SM ，Fan RF ，Wang L ... -  《-》

Protective effects of proanthocyanidins against cadmium-induced testicular injury through the modification of Nrf2-Keap1 signal path in rats.

The purpose of this study was to evaluate the potential chemoprotective effects of proanthocyanidins (PAs) against cadmium (Cd)-induced oxidative damage of testes via Nrf2-Keap1 signal pathway in rats. Briefly, by using biochemical histological analysis, as well as the real time PCR and western blot approach, oxidative damage in rat testicular tissue was observed after exposure to Cd. In addition, significant down-regulations of mRNA and protein levels of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), γ-glutamyl cysteine synthetase (γ-GCS), glutathione peroxidase (GSH-Px) and quinone oxidoreductase 1 (NQO1), as well as a significant up-regulation of Kelch sample related protein-1 (Keap1) levels in testicular tissue were observed after Cd exposure. Notably, these alterations were reverted back to near normalcy in Cd+PAs group rats. In conclusion, PAs exhibited a significant chemopreventive potential against Cd-induced testicular oxidative damage in rats, possibly through the modification of Nrf2-Keap1 signal path.

He L ，Li P ，Yu LH ，Li L ，Zhang Y ，Guo Y ，Long M ，He JB ，Yang SH ... -  《-》

Involvement of Nrf2 and mitochondrial apoptotic signaling in trehalose protection against cadmium-induced kidney injury.

Fan RF ，Li ZF ，Zhang D ，Wang ZY ... -  《-》

Cadmium induced oxystress alters Nrf2-Keap1 signaling and triggers apoptosis in piscine head kidney macrophages.

Cadmium (Cd) with no known functional role in any life-form has myriad of harmful effects. The present study was designed to elucidate the mechanism of Cd-induced oxystress generation and its impact on antioxidant and apoptosis signaling pathways in head kidney macrophage (HKM) of Channa punctatus Bloch. Fish were sampled and acclimatized with one group treated with cadmium chloride (CdCl2) (1.96 mg/L) and another as untreated control group, both kept under observation for 7 days. Exposure to Cd caused ultrastructural changes along with reduced head kidney somatic index (HKSI). Significantly increased levels of reactive oxygen species (ROS), respiratory burst activity, lipid peroxidation, DNA fragmentation and superoxide dismutase were found in the HKM from the treated group as compared to control. In contrast, antioxidant enzymes like catalase and reduced glutathione activity decreased in the Cd exposed group. The suppressed antioxidant activity was further confirmed and corroborated from the altered expression of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2) genes, the major player of antioxidant pathway. Cd induced alteration in Nrf2-Keap1 signaling pathway was also validated by the diminished levels of Nrf2 dependent expression of protein like heme oxygenase-1 (HO-1). The flow cytometry analysis supported the event of apoptosis in Cd exposed group as compared to control, which was further confirmed by the upregulated expression of caspase-3, caspase-8, caspase-9, TNF-α and p53 genes from the real-time gene expression study. In addition, altered protein level of cytochrome C validates the incidence of apoptosis. Altogether, our results demonstrate that exposure to Cd caused oxidative stress in HKM of Channa punctatus Bloch. by compromising the antioxidant enzyme activities via the down regulation of expression of genes related to antioxidant signaling pathway besides encouraging apoptosis via both mitochondrial and death receptor pathway.

Choudhury C ，Mazumder R ，Kumar R ，Dhar B ，Sengupta M ... -  《-》

Puerarin reverses cadmium-induced lysosomal dysfunction in primary rat proximal tubular cells via inhibiting Nrf2 pathway.

Wang LY ，Fan RF ，Yang DB ，Zhang D ，Wang L ... -  《-》