Lycopene Attenuates Di(2-ethylhexyl) Phthalate-Induced Mitochondrial Damage and Inflammation in Kidney via cGAS–STING Signaling

Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a highly harmful and persistent environmental pollutant. Due to its unique chemical composition, it frequently dissolves and enters the environment to endanger human and animal health. Lycopene is a natural bioactive component that can potentially reduce the risk of environmental factor-induced chronic diseases. The present study sought to explore the role and underlying mechanism of lycopene (LYC) on DEHP-induced renal inflammatory response and apoptosis. In this study, mice were orally treated with LYC (5 mg/kg BW/day) and/or DEHP (500 or 1000 mg/kg BW/day) for 28 days. Our results indicated that LYC prevented DEHP-induced histopathological alterations and ultrastructural injuries, including decreased mitochondrial membrane potential (ΔΨm), PINK1/Parkin pathway-mediated mitophagy, and mitochondrial energetic deficit. When damaged mitochondria release mitochondrial DNA (mtDNA) into cytosol, LYC can alleviate inflammation and apoptosis caused by DEHP exposure by activating the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS–STING) signal pathway. Collectively, our data demonstrate that LYC can reduce mitophagy caused by DEHP exposure by activating the PINK1/Parkin pathway and then reduce renal inflammation and apoptosis through the cGAS–STING pathway.

Lycopene Protects against Atrazine-Induced Kidney STING-Dependent PANoptosis through Stabilizing mtDNA via Interaction with Sam50/PHB1

“…12,39 Our findings suggest that exposure to ATR leads to interstitial hemorrhage and inflammatory infiltration near the glomeruli and enlarges the cystic lumen to 3.41 and 5.83 times the original size in the A50 and A200 groups, respectively. Previous studies have shown that LYC attenuates renal cortical injury, inflammatory cell infiltration, 40 and apoptosis, 41 and our results suggested that LYC alleviated ATR-induced interstitial hemorrhage and inflammatory infiltration and reduced the enlarged capsular lumen by 26 and 45%, respectively.…”

Inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by astragalus polysaccharide protects against transport stress-induced cardiac injury in chicks

“…Then, IRF7 enters the nucleus and activates the innate immune response ( Barrera et al, 2021 ; Lv et al, 2023 ). A previous study demonstrated that lycopene alleviates renal mitochondrial injury and inflammation induced by plasticizers through the cGAS-STING signaling pathway ( Li et al, 2023 ). Moreover, a study on necrotic enteritis in poultry has shown that dietary chlorogenic acid supplementation can prevent gut inflammation and damage by inhibiting the mtDNA-mediated cGAS-STING signaling pathway ( Lv et al, 2023 ), which supports our findings.…”

Lianweng Granules Alleviate Intestinal Barrier Damage via the IL-6/STAT3/PI3K/AKT Signaling Pathway with Dampness-Heat Syndrome Diarrhea

“…RNA was reverse-transcribed into complementary DNA (cDNA) using a commercial kit (Thermo Fisher Scientific, Waltham, MA, USA) and a T100 (Bio-Rad, Hercules, CA, USA) thermocycler. The mRNA levels in the colon were detected by GoScript Reverse Transcription System (Promega Biotech, Beijing, China) on a CFX 96 real-time system instrument (Bio-Rad, Hercules, CA, USA) with the following amplification program: 95 °C 120 s and 45 cycles of 95 °C for 5 s, 64 °C for 30 s and 72 °C for 30 s using specific primers ( Table S2 ) [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. The housekeeping gene beta-actin was used to standardize the gene expression, and the relative expression level of each gene was calculated using the 2 −ΔΔCT method [ 31 ].…”