ReferenceID 4569
Arctigenin alleviates cadmium-induced nephrotoxicity: Targeting endoplasmic reticulum stress, Nrf2 signaling, and the associated inflammatory response
Life Sci
AIM: Nephrotoxicity is a critical consequence of cadmium toxicity. Cadmium induces nephrotoxicity through disruption of cellular redox balance and induction of endoplasmic reticulum stress (ERS) and inflammatory response
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Record Fields
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- Reference Id
- 4569
- Evidence Id
- 21159
- Core Evidence Id
- 21159
- Source Reference Id
- 2407
- Herb2 Reference Id
- HBREF003204
- Subject Paper Key
- HBIN016609_34742745
- Pubmed Id
- 34742745
- Doi
- 10.1016/j.lfs.2021.120121
- Paper Title
- Arctigenin alleviates cadmium-induced nephrotoxicity: Targeting endoplasmic reticulum stress, Nrf2 signaling, and the associated inflammatory response
- Paper Abstract
- AIM: Nephrotoxicity is a critical consequence of cadmium toxicity. Cadmium induces nephrotoxicity through disruption of cellular redox balance and induction of endoplasmic reticulum stress (ERS) and inflammatory responses. The present study investigated the renoprotective effects of the naturally occurring arctigenin against the cadmium-induced nephrotoxicity. MAIN METHODS: Male Wistar rats were randomized into normal control, arctigenin control, cadmium, and cadmium/arctigenin groups. Cadmium and arctigenin were administered daily over a seven-day period. On the eighth day, blood and kidney tissue specimens were collected and subjected to spectrophotometric, ELISA, and immunoblotting analysis. KEY FINDINGS: Arctigenin significantly improved renal functions and reduced renal tubular injury in the cadmium-intoxicated rats as reflected by increased GFR and reduced levels of serum creatinine, BUN, urinary albumin-to-creatinine ratio, and protein expression of KIM-1. Arctigenin alleviated the cadmium-induced oxidative DNA damage and lipid peroxidation while boosted reduced glutathione level and antioxidant enzymes activity. Mechanistically, arctigenin enhanced nuclear translocation of the antioxidant transcription factor Nrf2 and up-regulated its downstream redox-regulating enzymes HO-1 and NQO1. Importantly, arctigenin ameliorated the cadmium-evoked ERS as demonstrated by reduced protein expression of the key molecules Bip, PERK, IRE1alpha, CHOP, phspho-eIF2alpha, and caspase-12 and diminished activity of caspase-12. Additionally, arctigenin down-regulated the cadmium-induced NF-kappaB nuclear translocation and decreased its downstream pro-inflammatory cytokines TNF-alpha and IL-1beta. SIGNIFICANCE: The current work underlines the alleviating activity of arctigenin against cadmium-evoked nephrotoxicity potentially through mitigating ERS and targeting Nrf2 and NF-kappaB signaling. The current findings support possible therapeutic application of arctigenin in controlling cadmium-induced nephrotoxicity although clinical investigations are necessary.
- Journal
- Life Sci
- Publish Year
- 2021
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Cadmium-induced Nephrotoxicity; Renal Tubular Injury
- Paper Title Cn
- Paper Title En
- Arctigenin alleviates cadmium-induced nephrotoxicity: Targeting endoplasmic reticulum stress, Nrf2 signaling, and the associated inflammatory response
- Bilingual Status
- semi_complete