Aflatoxin B1 (AFB1) pollutes foodstuffs and feeds, causing a food safety problem and seriously endangering human and animal health. Liver is the principal organ for AFB1 accumulation and ...biotransformation, during which AFB1 can cause acute and chronic liver damage, however, the specific mechanism is not completely clear. Mitochondria are the primary organelle of cellular bio-oxidation, providing 95% energy for liver to execute its multiple functions. Therefore, we speculated that mitochondrial dysfunction is involved in AFB1-induced liver injury. To verify the hypothesis, a total of eighty healthy male mice were randomly divided into four groups on average, and exposed with 0, 0.375, 0.75 and 1.5 mg/kg body weight AFB1 by intragastric administration for 30 d. The results displayed that AFB1 triggered liver injury accompanied by oxidative stress. AFB1 exposure also damaged mitochondria structure, decreased mitochondrial membrane potential (MMP), as well as increased cytoplasmic cytochrome c (Cyt-c) protein expression, Bax, p53, Caspase-3/9 protein and/or mRNA expression levels and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine-5'-triphosphate (dUTP) nick end labeling (TUNEL) staining positive cells in mice liver. Meanwhile, AFB1 exposure elevated pyruvate content, inhibited tricarboxylic acid (TCA) cycle rate-limiting enzymes and electron transport chain (ETC) complexes I-V activities, disturbed ETC complexes I-V subunits mRNA expression levels and reduced adenosine triphosphate (ATP) level in mice liver. These results indicated that AFB1 destroyed mitochondrial structure, activated mitochondrion-dependent apoptosis and induced mitochondrial dysfunction. In addition, AFB1 disrupted mitochondrial biogenesis, presented as the abnormalities of protein and/or gene expression levels of voltage dependent anion channel protein 1 (VDAC1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (Nrf1) and mitochondrial transcription factor A (Tfam). This may contribute to hepatic and mitochondrial lesions induced by AFB1. These results provide a new perspective for elucidating the mechanisms of AFB1 hepatotoxicity.
Aflatoxin B1 induced mice liver and mitochondrial lesions, which is associated with the mitochondrial biogenesis inhibition. Display omitted
•Aflatoxin B1 (AFB1) induced liver injury of mice.•Mitochondrial dysfunction is involved in AFB1-induced mice liver.•Mitochondrial biogenesis involved in AFB1-induced liver mitochondrial dysfunction.
Aluminum (Al) alters iron regulatory factors content and leads to the changes in iron-related proteins causing iron accumulation. But limited evidence ascertains this hypothesis. Therefore, our ...experiment was conducted and four groups of male Wistar rats were orally administrated of 0, 50, 150, and 450 mg/kg BW/d aluminum chloride (AlCl
3
) for 90 days by drinking water, respectively. The cognitive function, pathological lesion of hippocampus, oxidative stress, as well as iron-related proteins and iron regulatory factors expression were detected. The results showed that AlCl
3
remarkably induced the oxidative stress and pathological lesion in the hippocampus and impaired the learning-memory ability. The contents of Al and iron increased in all AlCl
3
-exposed groups. Meanwhile, the increased divalent metal transporter 1 (DMT1) expression enhanced iron import and the decreased ferroportin 1 (Fpn1) expression reduced iron export in AlCl
3
-exposed groups. The iron accumulated and ferritin heavy chains (Fth) expression decreased in all AlCl
3
-exposed groups led to an increase in free iron. The study also showed that iron regulatory factor iron regulatory protein 2 (IRP2) was decreased and hepcidin was increased in AlCl
3
-exposed groups. The results indicated that AlCl
3
induces iron dyshomeostasis presenting as iron accumulation, the disordered expression of iron import, export, store, and regulatory proteins in rat hippocampus accompanied with oxidative stress, pathological lesion, and impaired learning-memory ability.
Aflatoxin B1 (AFB1) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious antioxidant capable of shielding the ...liver from oxidative harm. This study aimed to examine the damage caused by AFB1 on bovine hepatic cells and the protective role of allicin against AFB1-induced cytotoxicity. In this study, cells were pretreated with allicin before the addition of AFB1 for co-cultivation. Our findings indicate that AFB1 compromises cellular integrity, suppresses the expression of nuclear factor erythroid 2–related factor 2 (Nrf2). In addition, allicin attenuates oxidative damage to bovine hepatic cells caused by AFB1 by promoting the expression of the Nrf2 pathway and reducing cell apoptosis. In conclusion, the results of this study will help advance clinical research and applications, providing new options and directions for the prevention and treatment of liver diseases.
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•AFB1 exposure leads to oxidative stress and apoptosis in cow hepatocytes.•Allicin reduces AFB1-induced hepatocyte damage via Nrf2 signalling pathway.•Allicin enhances antioxidant enzyme activities, reduces oxidative stress.•Allicin inhibits AFB1-triggered apoptosis by modulating Caspase families.
Aflatoxin B1 (AFB1) is an extremely hazardous and unavoidable pollutant for cereals and feedstuff. AFB1 can cause testicular lesion, and how to alleviate its testicular toxicity has received much ...attention in recent years. Lycopene (LYC), a foodborne nutrient derived from red fruits and vegetables, has protective effects against sperm abnormality and testicular lesions. To confirm the beneficial effects and mechanisms of LYC on AFB1-induced testicular lesion, 48 male mice were exposed to 0.75 mg/kg AFB1 or/and 5 mg/kg LYC for consecutive 30 days. Results demonstrated the LYC significantly restored the lesions of testicular microstructure and ultrastructure, and sperm abnormalities in AFB1-exposed mice. Furthermore, LYC effectively attenuated AFB1-induced oxidative stress and mitochondrial damage, including ameliorative mitochondrial structural, and elevated mitochondrial biogenesis for maintaining mitochondrial function. Meanwhile, LYC resisted AFB1-induced mitochondrial-dependent apoptosis. In addition, LYC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and upregulated the Nrf2 signaling pathway. Collectively, our findings demonstrate LYC ameliorates AFB1-induced testicular lesion by attenuating oxidative stress and mitochondrial damage, which is related to the activation of Nrf2.
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•Lycopene (LYC) has protective effect against Aflatoxin B1 (AFB1)-induced testicular lesion.•LYC mitigates AFB1-induced testicular lesion via ameliorating oxidative stress.•LYC mitigates AFB1-induced testicular lesion via ameliorating mitochondrial damage.•Protective mechanism of LYC on AFB1-induced testicular lesion is related to the activation of Nrf2.
This study aimed to investigate the effects of zearalenone (ZEA) on piglet Sertoli cell (SC)-mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) based on mitochondrial fission, and to ...explore the molecular mechanism of ZEA-induced cell damage. After the SCs were exposed to the ZEA, the cell viability decreased, the Ca
levels increased, and the MAM showed structural damage. Moreover, glucose-regulated protein 75 (Grp75) and mitochondrial Rho-GTPase 1 (Miro1) were upregulated at the mRNA and protein levels. However, phosphofurin acidic cluster protein 2 (PACS2), mitofusin2 (Mfn2), voltage-dependent anion channel 1 (VDAC1), and inositol 1,4,5-trisphosphate receptor (IP3R) were downregulated at the mRNA and protein levels. A pretreatment with mitochondrial division inhibitor 1 (Mdivi-1) decreased the ZEA-induced cytotoxicity toward the SCs. In the ZEA + Mdivi-1 group, the cell viability increased, the Ca
levels decreased, the MAM damage was repaired, and the expression levels of Grp75 and Miro1 decreased, while those of PACS2, Mfn2, VDAC1, and IP3R increased compared with those in the ZEA-only group. Thus, ZEA causes MAM dysfunction in piglet SCs through mitochondrial fission, and mitochondria can regulate the ER via MAM.
Aluminum (Al) is the most abundant metal in the earthâs crust. Al accumulates in erythrocyte and causes toxicity on erythrocyte membrane. The dysfunction of erythrocyte membrane is a potential risk ...to hypertension. The high Al content in plasma was associated with hypertension. To investigate the effect of AlClâ on blood pressure and the function of erythrocyte membrane, the rats were intragastrically exposed to 0, 64(1/20 LDâ â), 128(1/10 LDâ â), and 256(1/5 LDâ â)âmg/kg body weight AlClâ in double distilled water for 120 days, respectively. Then, we determined the systolic and mean arterial blood pressures of rats, the osmotic fragility, the percentage of membrane proteins, the activities of Naâº/Kâº-ATPase, Mg²âº-ATPase, Ca²âº-ATPase, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-pX), and malondialdehyde (MDA) content of the erythrocyte membrane in this experiment. The results showed that AlClâ elevated the systolic and mean arterial blood pressure of rats, increased the osmotic fragility, decreased the percentage of membrane protein, inhibited the activities of Naâº/Kâº-ATPase, Mg²âº-ATPase, Ca²âº-ATPase, CAT, SOD and GSH-pX, and increased the MDA content of erythrocyte membrane. These results indicate that AlClâ may induce hypertension by disturbing the function of erythrocyte membrane.
Aflatoxin B1 (AFB1) is a hazard environmental pollutants and the most toxic one of all the aflatoxins. AFB1 can cause a serious impairment to testicular development and spermatogenesis, yet the ...underlying mechanisms remain inconclusive. Oxidative stress acts as a master mechanism of AFB1 toxicity, and can promote autophagy. Abnormal autophagy resulted in testicular damage and spermatogenesis disorders. The objective of this study was to explore the effect of AFB1 on autophagy in mice testis and its potential mechanisms. In this study, male mice were intragastrically administered with 0, 0.375, 0.75 or 1.5 mg/kg body weight AFB1 for 30 days. We found that AFB1 induced testicular damage, reduced serum testosterone level and impaired sperm quality accompanied with the elevation of oxidative stress and germ cell apoptosis. Interestingly, we observed increasing numbers of autophagosomes in AFB1-exposed mice testis. Meanwhile, AFB1 caused testis abnormal autophagy with the characterization of increased expressions of LC3, Beclin-1, Atg5 and p62. Furthermore, AFB1 downregulated the expressions of PI3K, p-AKT and p-mTOR in mice testis. Taken together, our data indicated AFB1 induced testicular damage and promoted autophagy, which were associated with oxidative stress-related PI3K/AKT/mTOR signaling pathway in mice testis.
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•AFB1 promoted autophagy in mice testis.•AFB1-induced mice testicular damage was related to the abnormal autophagy.•AFB1 promoted autophagy related with oxidative stress-related PI3K/AKT/mTOR pathway.
AFB1-induced testicular damage accompanied by the abnormal autophagy, which was associated with oxidative stress-related PI3K/AKT/mTOR signaling pathway in mice.
Deoxynivalenol (DON) is an unavoidable cereal crops contaminants and environmental pollutants, which seriously threated the health of human and animal. DON has been reported to exert significant ...toxicity effects on spermatogenesis, but the underlying mechanisms remain largely inconclusive. The blood-testis barrier (BTB) provides a specialized biochemical microenvironment for maintaining spermatogenesis. Thus, we hypothesized that DON could impair BTB and lead to spermatogenesis disorder. To confirm this hypothesis, sixty male mice were intragastrically administered with 0, 1.2, 2.4 and 4.8 mg/kg body weight DON for 28 days, and several important observations were obtained in present study. First, we found that DON induced spermatogenesis disorder, reflected by the declines of sperm concentration and quality, sperm ultrastructural damage as well as seminiferous tubular damage. Then, we proved that DON induced BTB disruption as well as decreased the expressions of BTB junction proteins, including Occludin, Connexin 43 and N-cadherin. Finally, the present study showed that DON induced inflammation and inhibited T biosynthesis in testis of mice. These results revealed that DON induced spermatogenesis disorder by BTB disruption associated with testosterone deficiency and inflammation in mice, which shed a new light on the potential mechanisms of reproductive toxicity induced by DON.
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•Deoxynivalenol induced blood-testis barrier disruption in mice.•Deoxynivalenol inhibited testosterone biosynthesis in mice testis.•Deoxynivalenol induced inflammation in mice testis.
Capsule: Deoxynivalenol induced spermatogenesis disorder by blood-testis barrier disruption associated with testosterone deficiency and inflammation in mice.
T-2 toxin is an unavoidable contaminant in human food, animal feeds, and agricultural products. T-2 toxin has been found to impair male reproductive function. But, few data is available that reveals ...the reproductive toxicity mechanism. In the study, male Kunming mice were orally administrated with T-2 toxin at the doses of 0, 0.5, 1 or 2 mg/kg body weight for 28 days. The body and reproductive organs weight, the concentration, malformation rate and ultrastructure of sperm in cauda epididymis were detected. Oxidative stress biomarkers and apoptosis were also measured in testes. Histological change of testes was performed by H&E and TUNEL staining. T-2 toxin down-regulated body and reproductive organs (testis, epididymis and seminal vesicle) weight, sperm concentration, increased sperm malformation rate and damaged the ultrastructure of sperm and structure of testes. T-2 toxin treatment increased the reactive oxygen species (ROS) and malondialdehyde content, while, decreased the total anti-oxidation capacity (T-AOC) and the superoxide dismutase activity in testes. T-2 toxin exposure increased the TUNEL-positive germ cells, the activities and mRNA expressions of caspase-3, caspase-8 and caspase-9, the mRNA expression of Bax, and inhibited the Bcl-2 mRNA expression. Furthermore, the expressions of caspase-3, caspase-8 caspase-9 and Bax were positively correlated with ROS level, but negatively correlated with T-AOC in testis. In summary, T-2 toxin caused spermatogenesis disorder associated with the germ cell apoptosis medicated by oxidative stress, impairing the male reproductive function.
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•T-2 toxin damaged the testis histology and ultrastructure of sperm.•T-2 toxin impaired spermatogenesis on male mice.•T-2 toxin caused germ cell apoptosis by inducing oxidative stress in testis.
T-2 toxin inhibited spermatogenesis by causing germ cell apoptosis mediated by oxidative stress.
T-2 toxin, an inevitable environmental pollutant, is the most toxic type A trichothecene mycotoxin. Reproductive disruption is a key adverse effect of T-2 toxin. Herein, this paper reviews the ...reproductive toxicity of T-2 toxin and its mechanisms in male and female members of different species. The reproductive toxicity of T-2 toxin is evidenced by decreased fertility, disrupted structures and functions of reproductive organs, and loss of gametogenesis in males and females. T-2 toxin disrupts the reproductive endocrine axis and inhibits reproductive hormone synthesis. Furthermore, exposure to T-2 toxin during pregnancy results in embryotoxicity and the abnormal development of offspring. We also summarize the research progress in counteracting the reproductive toxicity of T-2 toxin. This review provides information toward a comprehensive understanding of the reproductive toxicity mechanisms of T-2 toxin.
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