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

Atrazine (ATR) is a widely used herbicide worldwide that can cause kidney damage in humans and animals by accumulation in water and soil. Lycopene (LYC), a carotenoid with numerous biological activities, plays an important role in kidney protection due to its potent antioxidant and anti-inflammatory effects. The current study sought to investigate the role of interactions between mtDNA and the cGAS-STING signaling pathway in LYC mitigating PANoptosis and inflammation in kidneys induced by ATR exposure. In our research, 350 mice were orally administered LYC (5 mg/kg BW/day) and ATR (50 or 200 mg/kg BW/day) for 21 days. Our results reveal that ATR exposure induces a decrease in mtDNA stability, resulting in the release of mtDNA into the cytoplasm through the mPTP pore and the BAX pore and the mobilization of the cGAS-STING pathway, thereby inducing renal PANoptosis and inflammation. LYC can inhibit the above changes caused by ATR. In conclusion, LYC inhibited ATR exposure-induced histopathological changes, renal PANoptosis, and inflammation by inhibiting the cGAS-STING pathway. Our results demonstrate the positive role of LYC in ATR-induced renal injury and provide a new therapeutic target for treating renal diseases in the clinic.

Exogenous Melatonin Alleviates Atrazine-Induced Glucose Metabolism Disorders in Mice Liver via Suppressing Endoplasmic Reticulum Stress.

Atrazine (ATZ) is a widely used herbicide that has toxic effects on animals. Melatonin (MLT) is a natural hormone with strong antioxidant properties. However, the effect of MLT on the glucose metabolism disorder caused by ATZ is still unclear. Mice were divided into four groups randomly and given 21 days of gavage: blank control group (Con), 5 mg/kg MLT group (MLT), 170 mg/kg ATZ group (ATZ), and 170 mg/kg ATZ and 5 mg/kg MLT group (ATZ + MLT). The results show that ATZ alters mRNA levels of metabolic enzymes related to glycogen synthesis and glycolysis and increased metabolites (glycogen, lactate, and pyruvate). ATZ causes abnormalities in glucose metabolism in mouse liver, interfering with glycemia regulation ability. MLT can regulate the endoplasmic reticulum to respond to disordered glucose metabolism in mice liver. This study suggested that MLT has the power to alleviate the ATZ-induced glycogen overdeposition and glycolytic deficit.

Holistic Assessment Based On Hepatocyte Mitochondria: Lycopene Repairs Oxidized mtDNA to Alleviate Mitochondrial Stress Induced by Atrazine.

Atrazine (ATZ) is a highly persistent herbicide that harms organism health. Lycopene (LYC) is an antioxidant found in plants and fruits. The aim of this study is to investigate the mechanisms of atrazine-induced mitochondrial damage and lycopene antagonism in the liver. The mice were divided into seven groups by randomization: blank control (Con group), vehicle control (Vcon group), 5 mg/kg lycopene (LYC group), 50 mg/kg atrazine (ATZ1 group), ATZ1+LYC group, 200 mg/kg atrazine (ATZ2 group), and ATZ2+LYC group. The present study performed a holistic assessment based on mitochondria to show that ATZ causes the excessive fission of mitochondria and disrupts mitochondrial biogenesis. However, the LYC supplementation reverses these changes. ATZ causes increased mitophagy and exacerbates the production of oxidized mitochondrial DNA (Ox-mtDNA) and mitochondrial stress. This study reveals that LYC could act as an antioxidant to repair Ox-mtDNA and restore the disordered mitochondrial function caused by ATZ.

Effect of atrazine on testicular toxicity involves accommodative disorder of xenobiotic metabolizing enzymes system and testosterone synthesis in European quail (Coturnix coturnix).

Due to the wide use of atrazine (ATR), the concern has increased regarding the negative impact of ATR on reproduction. Nevertheless, the reproductive effects caused by different exposure concentrations and the severity of toxic damage are poorly understood. In organisms, ATR is metabolized and degraded through phase II enzyme systems, and changes in cytochrome P450 (CYP) enzymes may have a regulatory role in the harm of ATR. However, less information is available on the induction of CYPs by ATR in avian organisms, and even less on its effects on the testis. Birds are exposed to ATR mainly through food residues and contaminated water, the purpose of this study was to examine reproductive toxicity by different exposure concentrations and elaborate metabolic disorders caused by ATR in European quail (Coturnix coturnix). In this study, the quail were given ATR at 50 mg/kg, 250 mg/kg and 500 mg/kg by oral gavage for 45 days, and the testicular weight coefficients, histopathology and ultrastructure of testes, primary biochemical functions, sex steroid hormones, critical protein levels in the testosterone synthesis pathway, the expression of genes involved CYPs, gonad axis and nuclear receptors expression were investigated. Altogether, testicular coefficient decreased significantly in the high-dose group (1.22%) compared with the control group (3.03%) after 45 days of ATR exposure, and ATR is a potent CYP disruptor that acts through the NXRs and steroid receptor subfamily (APND, CAR, ERND and ERα) without a dose-dependent manner. Notably, ATR interfered with the homeostasis of hormones by triggering the expression of hormones on the gonad axis (LH and E2). These results suggest that exposure to ATR can cause testicular toxicity involving accommodative disorder of phase II enzyme and testosterone synthesis in European quail.

Mitocytosis Is Critical for Phthalate-Induced Injury to the Ovarian Granulosa Cell Layer in Quail (Coturnix japonica).

Phthalates are widely used synthetic chemicals that determine endocrine disruption effects on female reproductivity and oviposition. Our study demonstrated that the mitochondrial quality in ovarian granulosa cells (GCs) is associated with a poor prognosis in female reproduction. However, the molecular mechanism of di-(2-ethylhexyl) phthalate (DEHP) exposure on the quail ovarian GC layer is still unknown. To validate the effects of DEHP on the GC layer, 8 days' old 150 female Japanese quail were treated orally with DEHP (250, 500, and 750 mg/kg BW/day) for 45 days to explore the toxic effects of DEHP on the ovarian GC layer. Histopathological assessment and ultrastructure observation found that DEHP decreased the thickness of the GC layer, resulted in mitochondrial damage, and activated mitocytosis. Additionally, the results further suggested that DEHP impacted the secretion of steroid hormones (reduced FSH, E2, and T levels and boosted Prog, PRL, and LH levels) by triggering mitocytosis (enhanced transcription of MYO19 and protein of KIF5B levels), mitochondrial dynamics (increasing mRNA and protein levels of OPA1, DRP1, MFN1, and MFN2), mitophagy (increasing mRNA and protein levels of Parkin, LC3B, and P62), and inducing GC function disorder. In conclusion, our research provided a new idea to explain the mechanism of DEHP toxicity of the ovarian GC layer in quail and presented insights into the role of mitocytosis in DEHP-induced ovarian GC layer injury.