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1.
Toxicology ; 462: 152957, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34537261

RESUMO

Zearalenone (ZEN), a mycotoxin is frequently detected in different food products and has been widely studied for its toxicity. However, the underlying mechanisms of hepatotoxic effects, relationship between gut microbiome and liver metabolite mediated hepatotoxicity mechanisms induced by ZEN are still not clear. Here, we reported that the different microscopic changes like swelling of hepatocyte, disorganization of hepatocytes and extensive vacuolar degeneration were observed, and the mitochondrial functions decreased in exposed mice. Results exhibited up-regulation in expression of signals of apoptosis and autophagy in liver of treated mice via mitochondrial apoptotic and autophagy pathway (Beclin1/p62). The diversity of gut microbiome decreased and the values of various microbiome altered in treated mice, including 5 phyla (Chloroflexi, Sva0485, Methylomirabilota, MBNT15 and Kryptonia) and genera (Frankia, Lactococcus, Anaerolinea, Halomonas and Sh765B-TzT-35) significantly changed. Liver metabolism showed that the concentrations of 91 metabolite including lipids and lipid like molecules were significantly changed. The values of phosphatidylcholine, 2-Lysophosphatidylcholine and phosphatidate concentrations suggestive of abnormal glycerophosphate metabolism pathway were significantly increased in mice due to exposure to ZEN. In conclusion, the findings suggest that the disorders in gut microbiome and liver metabolites due to exposure to ZEN in mice may affect the liver.

2.
Environ Sci Pollut Res Int ; 28(39): 55140-55153, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34128171

RESUMO

Copper (Cu) is a heavy metal which is being used widely in the industry and agriculture. However, the overuse of Cu makes it a common environmental pollutant. In order to investigate the testicular toxicity of Cu, the pigs were divided into three groups and were given Cu at 10 (control), 125, and 250 mg/kg body weight, respectively. The feeding period was 80 days. Serum hormone results showed that Cu exposure decreased the concentrations of follicular stimulating hormone (FSH) and luteinizing hormone (LH) and increased the concentration of thyroxine (T4). Meanwhile, Cu exposure upregulated the expression of Cu transporter mRNA (Slc31a1, ATP7A, and ATP7B) in the testis, leading to increase in testicular Cu and led to spermatogenesis disorder. The Cu exposure led to an increased expression of antioxidant-related mRNA (Gpx4, TRX, HO-1, SOD1, SOD2, SOD3, CAT), along with increase in the MDA concentration in the testis. In LG group, the ROS in the testis was significantly increased. Furthermore, the apoptotic-related mRNA (Caspase3, Caspase8, Caspase9, Bax, Cytc, Bak1, APAF1, p53) and protein (Active Caspase3) and the autophagy-related mRNA (Beclin1, ATG5, LC3, and LC3B) expression increased after Cu exposure. The mitochondrial membrane potential in the testicular tissue decreased, while the number of apoptotic cells increased, as a result of oxidative stress. Overall, our study indicated that the Cu exposure promotes testicular apoptosis and autophagy by mediating oxidative stress, which is considered as the key mechanism causing testicular degeneration as well as dysfunction.


Assuntos
Cobre , Testículo , Animais , Apoptose , Autofagia , Cobre/toxicidade , Masculino , Estresse Oxidativo , Suínos
3.
Biomed Res Int ; 2021: 8871328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33532499

RESUMO

Acetyl-L-carnitine (ALC) is an effective substrate for mitochondrial energy metabolism and is known to prevent neurodegeneration and attenuate heavy metal-induced injury. In this study, we investigated the function of ALC in the recovery of mouse spermatogonia cells (GC-1 cells) after heat stress (HS). The cells were randomly divided into three groups: control group, HS group (incubated at 42°C for 90 min), and HS + ALC group (treatment of 150 µM ALC after incubated at 42°C for 90 min). After heat stress, all of the cells were recovered at 37°C for 6 h. In this study, the content of intracellular lactate dehydrogenase (LDH) in the cell supernatant and the malondialdehyde (MDA) levels, catalase (CAT) levels, and total antioxidant capacity (T-AOC) were significantly increased in the HS group compared to the CON group. In addition, the mitochondrial membrane potential (MMP) was markedly decreased, while the apoptosis rate and the expression of apoptosis-related genes (Bcl-2, Bax, and caspase3) were significantly increased in the HS group compared to the CON group. Furthermore, the number of autophagosomes and the expression of autophagy-related genes (Atg5, Beclin1, and LC3II) and protein levels of p62 were increased, but the expression of LAMP1 was decreased in the HS group compared to the CON group. However, treatment with ALC remarkably improved cell survival and decreased cell oxidative stress. It was unexpected that levels of autophagy were markedly increased in the HS + ALC group compared to the HS group. Taken together, our present study evidenced that ALC could alleviate oxidative stress and improve the level of autophagy to accelerate the recovery of GC-1 cells after heat stress.


Assuntos
Acetilcarnitina/farmacologia , Autofagia/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espermatogônias/citologia
4.
Chemosphere ; 272: 129572, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33485040

RESUMO

Atrazine (ATR), a bio accumulative herbicide is frequently used in agriculture to control unwanted weeds. Due to continuous application, atrazine persists in the environment and causes deleterious impacts including neurotoxicity, hepatotoxicity, and gut microbiota disorders. Therefore, this study for the first time reports the variation in the gut microbiota, induction of process of apoptosis and autophagy in mice induced by ATR. Results indicated that TUNEL-positive hepatocytes suggestive of apoptosis were increased in livers of different experimental mice. Results on metabolic analysis in liver tissues indicated an overall change in seventy-six metabolites particularly Uridine 5'-diphosphate, Propenoylcarnitine and Chinenoside V resulting in generation of energy-related metabolic disorders and imbalance of oxidation/autoxidation status. Results on gut microbiome inquisition showed that ATR changed the richness and diversity of gut microbiota of mice and number of Firmicutes. Moreover, results also revealed that ATR induced apoptosis via disruption of apoptotic (Bax, Bcl2, and Casp3) and autophagy (LC3/Map1lc3a, Beclin 1/Becn1 and P62/Sqstm1) genes. Results of our experimental study confirmed that changes in gut microbiota play a significant role in process of gut immune regulation and inflammation via different metabolites. In conclusion, the findings of our study provide a new idea for the involvement of mechanisms of detoxification in liver and inquisition of gut microbiota plays crucial role in regulation of physiological activities through liver-gut axis to mitigate toxic effects in animals.


Assuntos
Atrazina , Doença Hepática Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Herbicidas , Animais , Atrazina/toxicidade , Autofagia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Camundongos
5.
Ecotoxicol Environ Saf ; 190: 110063, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846860

RESUMO

Arsenic is a toxic metalloid that can cause male reproductive malfunctions and is widely distributed in the environment. The aim of this study was to investigate the cytotoxicity of arsenic trioxide (ATO) induced GC-1 spermatogonial (spg) cells. Our results found that ATO increased the levels of catalase (CAT) and malonaldehyde (MDA) and reactive oxygen species (ROS), while decreasing glutathione (GSH) and the total antioxidant capacity (T-AOC). Therefore, ATO triggered oxidative stress in GC-1 spg cells. In addition, ATO also caused severe mitochondrial dysfunction that included an increase in residual oxygen consumption (ROX), and decreased the routine respiration, maximal and ATP-linked respiration (ATP-L-R), as well as spare respiratory capacity (SRC), and respiratory control rate (RCR); ATO also damaged the mitochondrial structure, including mitochondrial cristae disordered and dissolved, mitochondrial vacuolar degeneration. Moreover, degradation of p62, LC3 conversion, increasing the number of acidic vesicle organelles (AVOs) and autophagosomes and autolysosomes are demonstrated that the cytotoxicity of ATO may be associated with autophagy. Meanwhile, the metabolomics analysis results showed that 20 metabolites (10 increased and 10 decreased) were significantly altered with the ATO exposure, suggesting that maybe there are the perturbations in amino acid metabolism, lipid metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins. We concluded that ATO was toxic to GC-1 spg cells via inducing oxidative stress, mitochondrial dysfunction and autophagy as well as the disruption of normal metabolism. This study will aid our understanding of the mechanisms behind ATO-induced spermatogenic toxicity.


Assuntos
Trióxido de Arsênio/toxicidade , Autofagia/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Lisossomos/metabolismo , Masculino , Metabolômica , Camundongos , Mitocôndrias/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Espermatogônias/enzimologia , Espermatogônias/metabolismo
6.
Biol Trace Elem Res ; 195(2): 472-480, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31444770

RESUMO

Chronic copper exposure impaired spermatogenesis in adult male mice. The aim of this study was to determine whether chronic copper exposure can induce apoptosis of testicular cell and hypospermatogenesis via disturbing testosterone synthesis in adult male mice. In the present study, sixty CD-1 male mice were randomly divided into four groups, and were continuously administered for 8 weeks by oral gavage with copper sulfate at a dose of 0, 25, 100, and 150 mg/kg/day, respectively. We determined the content of serum and testicular copper, testicular coefficient, testicular histopathology, sperm count and motility, the mRNA and protein levels of Caspase-3, Bax, and Bcl-2, Leydig cell count, testosterone content, testosterone synthetase, and testosterone synthesis-related genes. The results showed that the copper levels in serum increased in a dose-dependent manner, and the copper levels in testes were significantly related to serum copper levels. Male mice given copper sulfate 100 and 150 dosage groups showed significant decreased in sperm motility and sperm number as well as increased in testes damage, and there was no significant change in testicular coefficient in the four groups. The mRNA levels of Bcl-2 decreased and Caspase-3 increased in 150 dosage group, and Bax increased in two higher dosage groups. Meanwhile, Caspase-3 and Bax proteins increased in 150 dosage group, and Bcl-2 protein decreased in three copper treatment groups. Nevertheless, there were no differences on the levels of testosterone content and testosterone synthetase of 3ß-HSD, 17ß-HSD, 17α-Hyd, and 20α-Hyd, mRNA levels of Cyp11a1, Cyp17a1, and Star, and quantity of Leydig cells in four groups. Overall, these data showed that chronic copper exposure led to copper residues in the testes, and the doses of 100 and 150 mg/kg/day copper sulfate may induce hypospermatogenesis by increasing apoptosis without affecting testosterone secretion.


Assuntos
Apoptose/efeitos dos fármacos , Sulfato de Cobre/farmacologia , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/metabolismo , Administração Oral , Animais , Sulfato de Cobre/administração & dosagem , Sulfato de Cobre/análise , Masculino , Camundongos , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue
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