Effects Of Mitochondrial Homeostasis On Resveratrol Antagonized Cadmium Induced Kidney Damage In Chickens

Cadmium?Cd?is a widely distributed agricultural environmental pollutant in the world.It has environmental persistence and bioaccumulation.Cadmium accumulation in animals poses a huge threat to animal health.Up to 50%of the cumulative dose after cadmium exposure is stored in the kidney,indicating that the kidney is the main target organ for cadmium toxicity.Resveratrol is a powerful antioxidant.It acts as a free radical scavenger during the oxidative stress reaction and interacts with many signal targets during antioxidant and mitochondrial biosynthesis.However,the protective mechanism of resveratrol against cadmium-induced kidney damage in chickens is unclear.In this study,chicken was used as an experimental object,with cadmium and resveratrol added to the diet.By observing kidney pathological tissue sections,kidney function,antioxidant function,mitochondrial ultrastructure,mitochondrial damage,mitochondrial dynamics and mitochondrial autophagy were detected.Comprehensively explored the molecular mechanism of resveratrol antagonizing cadmium-induced kidney toxicity in chickens.The results showed that:?1?Exposure to cadmium leads to severe vacuolation,glomerular atrophy,and expansion of the glomerular space in the renal tubular epithelial cells,which leads to increas ed serum BUN and CREB concentrations,resulting in damage to renal function;The combined action of resveratrol and cadmium can alleviate the pathological tissue damage of kidney caused by cadmium and restore kidney function.?2?Resveratrol can correct the CYP450 enzyme system disorder caused by cadmium exposure,reduce CYP450 content,activate the AHR/CAR/PXR-mediated nuclear receptor response,activate the phase?detoxification enzyme system,and antagonize cadmium-induced chicken kidneys toxicity.?3?Resveratrol can alleviate the decrease of T-AOC level caused by cadmium exposure,increase the activity of antioxidant enzymes?T-SOD,Cu-Zn SOD,GST,GSH-Px?,and reduce the production of oxidation products?MDA,H₂O₂?by activating the Nrf2 signaling pathway,up-regulating the expression of HO-1,NQO1 and GSTs can alleviate oxidative stress in chicken kidneys caused by cadmium exposure.?4?Exposure to cadmium can lead to ultrastructural changes in chicken kidneys,a larg e amount of swollen endoplasmic reticulum in the cytoplasm,autophagic vacuoles of varying sizes,and some containing damaged mitochondria,showing the typical"mitochondrial autophagy"The number of mitochondria increased significantly,and the bilayer me mbrane of mitochondria was obscured or even disappeared.After the combination of resveratrol and cadmium,the number of autophagic vesicles was significantly reduced,and the mitochondrial morphology was partially restored.?5?Cadmium exposure leads to a reduction in the transcription levels of mitochondrial function-related factors?Nrf1,PGC-1?,TFAM,SIRT1?and mitochondrial fusion-related factors?OPA1,MFN1,MFN2?,VDAC1,Cyt C and mitochondrial division-related factors?Fis1,MFF?Increased transcription level reduces mitochondrial biosynthesis,activates PINK1/Parkin signaling pathway-mediated mitochondrial autophagy,and triggers mitochondrial dysfunction;after combined use of resveratrol and cadmium,it restores mitochondrial biosynthesis,inh ibits excessive mitochondrial division and Mitochondrial autophagy can alleviate the damage of chicken kidney mitochondria caused by cadmium exposure.In summary,resveratrol can reduce the pathological histological damage of chicken kidneys caused by cadmium exposure,restore kidney function,and activate AHR/CAR/PXR-mediated nuclear xenobiotic receptor response and Nrf2-mediated antioxidant Defense,balance mitochondrial dynamics,inhibit excessive mitochondrial autophagy,and antagonize cadmium-induced chicken kidney toxicity.