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Excessive doses of molybdenum (Mo) and cadmium (Cd) have toxic effects on animals. Nevertheless, the reproductive toxicity elicited by Mo and Cd co-exposure remains obscure. To evaluate the co-induce toxic impacts of Mo and Cd on ovaries, 8-day-old 40 healthy ducks were stochastically distributed to four groups and were raised a basal diet supplemented with Cd (4 mg/kg Cd) and/or Mo (100 mg/kg Mo). In the 16th week, ovary tissues were gathered. The data revealed that Mo and/or Cd decreased GSH content, CAT, T-SOD, and GSH-Px activities and increased MDA and H 2 O 2 levels. Moreover, there was a significant decrease in nuclear Nrf2 protein level and its related downstream factors, while cytoplasmic Nrf2 protein level showed a substantial increase. Additionally, a marked elevation was observed in ferrous ion content and TFRC, GCLC, SLC7A11, ACSL4, and PTGS2 expression levels, while FTH1, FTL1, FPN1, and GPX4 expression levels were conversely reduced. These indicators exhibited more marked changes in the joint exposure group. In brief, our results announced that Mo and/or Cd resulted in oxidative stress and ferroptosis in duck ovaries. Synchronously, the Cd and Mo mixture intensified the impacts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Excess molybdenum (Mo) and cadmium (Cd) are harmful to animals, but the neurotoxic mechanism co-induced by Mo and Cd is unclear. To estimate the effects of Mo and Cd co-exposure on pyroptosis by nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant defense response in duck brains, 40 healthy 7-day-old ducks were randomly assigned to 4 groups and fed diet supplemented with Mo or/and Cd for 16 weeks, respectively. Results showed that Mo or/and Cd markedly increased Mo and Cd contents; decreased iron (Fe), copper (Cu), zinc (Zn), and selenium (Se) contents, elevated malondialdehyde (MDA) content; and decreased total-antioxidant capacity (T-AOC), total-superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities accompanied by pathological damage in brain. Additionally, Mo or/and Cd inhibited Nrf2 pathway via decreasing Nrf2, CAT, SOD1, glutathione S-transferase (GST), hemeoxygenase-1 (HO-1), NAD (P) H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), and modifier subunit (GCLM) mRNA levels and Nrf2 protein level, which induced pyroptosis through upregulating nucleotide oligomerization domain-like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein (ASC), gasdermin A (GSDMA), gasdermin E (GSDME), interleukin-1β (IL-1β), interleukin-18 (IL-18), Caspase-1, NIMA-related kinase 7 (NEK7) mRNA levels and NLRP3, Caspase-1 p20, gasdermin D (GSDMD), ASC protein levels and IL-1β, and IL-18 contents. Besides, the changes of these indicators were most apparent in the Mo and Cd co-treated group. Collectively, the results certificated that Mo and Cd might synergistically induce pyroptosis via inhibiting Nrf2-mediated antioxidant defense response in duck brains, whose mechanism is closely related to Mo and Cd accumulation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Twelve Kunming mice were randomly divided into two groups (n = 6), and administered with distilled water containing 0 mg/L and 160 mg/L HgCl 2 respectively, with an experimental period of 3 days. Our results showed that mercury exposure significantly reduced weight gain in mice (P < 0.01). Through pathological observation of cecum tissues, significant pathological changes were observed in cecum tissues of mice exposed to mercury. Furthermore, mercury exposure not only significantly increased malondialdehyde (MDA) content in mice (P < 0.01) but also significantly decreased superoxide dismutase (SOD) activity (P < 0.01) and glutathione peroxidase (GSH) level in mice (P < 0.01). Furthermore, high-throughput sequencing analysis showed that at the genus level some microbial populations including Clostridiales, Lactobacillus, Treponema, Oscillospira, and Desulfovibrio were significantly increased whereas some microbial populations including S24-7, Acinetobacter, and Staphylococcus were significantly decreased. Moreover, correlation analysis indicated that microorganisms were not correlated with biomarkers of oxidative stress. In summary, mercury exposure reduced the growth performance of mice, resulting in gut microbiota alterations, and led to oxidative stress by increasing the concentration of malondialdehyde (MDA) and decreasing the concentration of superoxide dismutase (SOD) and glutathione peroxidase (GSH).

The purpose of this study was to evaluate the effects of excessive molybdenum (Mo) on renal function and oxidative stress in goats. Twenty-seven healthy goats were randomly allotted in three groups and were fed deionized water to which sodium molybdate [(NH 4 ) 6 Mo 7 O 24 ·4H 2 O] was added at different doses of 0, 15, and 45 mg Mo/(kg·BW) for 50 days, respectively. The results indicated that white blood cell (WBC) counts were significantly increased (P < 0.05), while red blood cell (RBC) counts, hemoglobin (HGB), and mean corpuscular hemoglobin concentration (MCH) were tended to decrease with the increasing of the experimental period in high-Mo group compared with the control group. Besides, blood urea nitrogen (BUN) and creatinine (CREA) contents in serum were increased (P < 0.05) in both groups supplemented with molybdenum. Meanwhile, contents of copper (Cu) from the both experimental groups were significantly decreased (P < 0.05), while contents of zinc (Zn) and iron (Fe) were increased (P < 0.05) in serum. The contents of Cu were significantly increased (P < 0.05), while the contents of zinc (Zn) and iron (Fe) did not obviously change (P > 0.05) in the kidney. In addition, the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased (P < 0.05) in the mitochondria, whereas malondialdehyde (MDA) and nitric oxide synthase (NOS) expression significantly increased (P < 0.05). Collectively, these results indicated that excess Mo exposure could induce secondary Cu deficiency and oxidative stress in the kidney, which finally undermine the renal function of goats.

The aim of the present study was to investigate the effects of high concentrations of copper (Cu) on the cecum and rectum of intestinal microbiota in female mice. Twenty-four Kunming mice were weighed and randomly divided into two groups (n = 12 per group) including the control group and Cu group. Cu group was given drinking water with 5 mg/kg-bw copper chloride (CuCl 2 ), while the control group was treated with drinking water without CuCl 2 . At the 90th day, results showed that compared with the control group, mice in the treatment group had a lower body weight, and the feces turned yellow and had a lower pH value. Histopathological lesions showed that the intestinal tissue from the treatment group had increased thickness of outer muscularis and smoothed muscle fiber, widened submucosa, decreased goblet cells, and showed blunting of intestinal villi and severe atrophy of central lacteal. In addition, at the genus level, 16S rRNA gene sequencing from the Cu group showed that Corynebacterium were significantly increased whereas Staphylococcaceae, Odoribacter, Rikenella, and Jeotgalicoccus were significantly decreased in the cecum. Dehalobacterium, Coprococcus, and Spirochaetales increased significantly whereas Salinicoccus, Bacillales, Staphylococcus, and Lactobacillales decreased sharply in the rectum. This study demonstrated that high concentrations of Cu could induce tissue injury and interrupt the homeostasis of microbiota.

The aim of the present study was to investigate the effects of high doses of copper (Cu) and mercury (Hg) on the cecal microbiota in female mice. Forty-eight Kunming mice were randomly divided into the control group (CCk group), the Cu group (CCu group), the Hg group (CHg group), and the Cu + Hg group (CCH group). At the 90th day, cecal tissues were prepared for histopathological analysis and cecal contents for analysis by 16S rRNA sequencing method. Cecal tissues from treatment groups had histopathological lesions including increased thickness of inner muscularis and outer muscularis, widened submucosa, decreased goblet cells, mild to moderate necrosis of enterocytes, blunting of intestinal villi, and severe atrophy of central lacteal. Furthermore, compared to the CCk group, the abundance of bacteria genera Rikenella, Jeotgailcoccus, and Staphylococcus were significantly decreased, whereas the bacteria genus Corynebacterium was significantly increased in the CCu group. The abundance of bacteria genera of Sporosarcina, Jeotgailcoccus, and Staphylococcus were significantly decreased in the CHg group and CCH group. The bacteria genus Anaeroplasma was significantly increased in the CCH group. The results indicated that high doses of Cu and Hg caused histopathological lesions and changed the diversity of microbiota in the cecum of female mice, which provide a theoretical basis for more accurate assessment of the risk in intestinal diseases caused by Cu and Hg.

Cadmium (Cd) and high molybdenum (Mo) can lead to adverse reactions on animals, but the coinduced toxicity of Mo and Cd to bone in ducks was not well understood. The objective of this study was to investigate the changes in trace elements' contents and morphology in bones of duck exposed to Mo or/and Cd. One hundred twenty healthy 11-day-old male ducks were randomly divided into six groups and treated with commercial diet containing Cd or/and Mo. On the 60th and 120th days, the blood, excretion, and metatarsals were collected to determine alkaline phosphatase (ALP) activity and the contents of Mo, Cd, calcium (Ca), phosphorus (P), copper (Cu), iron (Fe), zine (Zn), and selenium (Se). In addition, metatarsals were subjected to histopathological analysis with the optical microscope and radiography. The results indicated that Mo and Cd contents significantly increased while Ca, P, Cu, and Se contents remarkably decreased in metatarsals in coexposure groups (P < 0.01). Contents of Fe and Zn in metatarsals had no significant difference among groups (P > 0.05). Ca content in serum had no significant difference among experimental groups (P > 0.05), but P content was significantly decreased in HMo and HMo + Cd groups (P < 0.05). Contents of Ca and P in excretion and ALP activity were significantly increased in coinduced groups (P < 0.05). Furthermore, osteoporotic lesions, less and thinner trabecular bone were observed in combination groups. The findings suggested that dietary of Cd or/and Mo could lead to bone damages in ducks via disturbing the balance of Ca and P in body and homeostasis of Cu, Fe, Zn, and Se in bones; moreover, the two elements showed a possible synergistic relationship.

Molybdenum (Mo) is an essential trace element for animals and human beings. However, the negative effects on rumen function and distribution of trace elements in tissues induced by excessive Mo have not been well understood. Therefore, the purpose of present study was to investigate the impact of Mo on rumen microbiota, distribution of trace elements in various organs, and hematological parameters of goats. A total of 36 goats were randomly distributed into three groups with equal number and low-Mo and high-Mo groups were orally administered ammonium molybdate at 15 and 45 mg · Mo · kg -1  · BW respectively, while the control group received corresponding quantitative deionized water. The results showed that the total number of ciliate and protozoa protein concentration decreased significantly (P < 0.01) on days 25 and 50. Concentrations of ammonia nitrogen and bacterial protein were significantly higher (P < 0.05) in low-Mo group, while they were lower (P < 0.05) in high-Mo group than the control group on days 25 and 50. In addition, Mo accumulated in serum and all detected tissues. Copper (Cu) and zinc (Zn) contents significantly decreased (P < 0.05) in hair and serum on days 25 and 50, while Cu contents increased (P < 0.05) and the change of Zn contents were not obvious (P > 0.05) in other tissues on days 25 and 50. Besides, there was no obvious variation in iron (Fe) contents during whole experiment period (P > 0.05). Furthermore, excessive Mo content had no significant effect on red blood cell (RBC) counts and hemoglobin (HGB) concentration (P > 0.05) on days 25 and 50, while white blood cell (WBC) counts increased significantly (P < 0.05) on day 50. These results indicated that excessive Mo content could impact the balance of ruminal microorganisms and interfere with the absorption and distribution of Mo and Cu mainly.

To investigate the effects of co-exposure to molybdenum (Mo) and cadmium (Cd) on oxidative stress and cell apoptosis in caprine livers, 36 Boer goats were randomly divided into four groups with nine goats in each group. Three groups were randomly assigned with one of three oral treatments of CdCl2 (0.5 mg Cd kg(-1)·BW) and [(NH4)6Mo7O24·4H2O] (15 mg Mo kg(-1)·BW, 30 mg Mo kg(-1)·BW, 45 mg Mo kg(-1)·BW), while the control group received deionized water. Liver tissues on days 0, 25, and 50 were subjected to determine antioxidant activity indexes and the messenger RNA (mRNA) expression levels of ceruloplasmin (CP), cysteinyl aspartate-specific proteinase-3 (caspase-3), second mitochondria-derived activator of caspases (Smac), and cytochrome-C (Cyt-C) genes. The results showed that significant reductions were observed in total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) activities (P < 0.05), while activities or contents of malondialdehyde (MDA), nitric oxide (NO), and nitric oxide synthase (NOS) were increased (P < 0.05). The mRNA expression levels of CP, caspase-3, Smac, and Cyt-C genes were upregulated (P < 0.05). In addition, histopathological lesions showed different degrees of vacuolar degeneration and edematous and mitochondrial swelling. The results suggest that co-exposure to Mo and Cd could induce oxidative stress and cell apoptosis possibly associated with mitochondrial intrinsic pathway in goat liver and show possible synergistic effects between the two elements.

Molybdenum (Mo) is an essential element for human beings and animals; however, high dietary intake of Mo can lead to adverse reactions. Cadmium (Cd) is one of the major transitional metals which have toxic effects in animals. The toxicity of simple Cd or Mo has been researched frequently. However, the toxicity of Mo combined with Cd was rarely studied. To investigate the toxicity of Mo combined with Cd in liver of goats, 36 Boer goats were randomly divided into four groups and assigned with one of the three oral treatments of CdCl2 (0.5 mg kg(-1) Cd) and [(NH4)6Mo7O24·4H2O] (15 mg kg(-1) Mo, group I; 30 mg kg(-1) Mo, group II; 45 mg kg(-1) Mo, group III), while the control group received deionized water. Blood samples were collected on days 0, 10, 20, 30, 40, and 50 to determine antioxidant indices in serum. In addition, liver tissues were collected on days 0, 25, and 50 for detecting the messenger RNA (mRNA) expression levels of Bcl-2 and Bax. Moreover, liver tissues at 50 days were subjected to histopathological analysis with the optical microscope. The results revealed a significant increase (P < 0.05 or P < 0.01) in the levels of nitric oxide (NO), malonaldehyde (MDA), and the activity of nitrix oxide synthase (NOS) and a significant decline (P < 0.05) in the activities of total superoxide dismutase (T-SOD) and total antioxidative capacity (T-AOC). The mRNA expression level of Bcl-2 was suppressed (P < 0.05), while the expression of Bax was increased (P < 0.05) in liver. The histopathological changes were observed in the liver of goats including a small amount of erythrocyte, the unclear structure of hepatic cord and hepatic sinusoid, granular degeneration, vacuolar degeneration, and steatosis. In conclusion, combined chronic toxicity of Cd with different levels of Mo might induce goat liver cell apoptosis and cause oxidative stress in serum, and it showed a possible synergistic relationship between the two elements.

The present experiment aims at evaluating chronic toxic effects of the combination of cadmium (Cd) and molybdenum (Mo) according to residual element contents, apoptosis gene expression, and ultrastructure and histopathology changes of caprine spleen. In total, 36 Boer goats were randomly divided into four groups with the equal number in each group. The control group was orally administered with deionized water while the experimental groups I, II, and III were administered with the equal quantity of CdCl2 (1 mg kg(-1) BW) and (NH4)6·Mo7O24·4H2O including 15, 30, and 45 mg·Mo kg(-1) BW, respectively. Three individuals from each group were treated with euthanasia on days 0, 25, and 50. The data showed that the content of splenic residual Mo and Cd increased (P < 0.05) in the experimental groups on days 25 and 50, while no significant difference was observed in the content of Cu. The apoptosis-related gene expression levels including Bcl-2, Bax, Caspase-3, Smac, and ceruloplasmin (CP) were also determined. Results showed that significant reductions were observed in Bcl-2 and CP expressions (P < 0.01), while Caspase-3 gene was up-regulated (P < 0.05). However, no significant difference was observed in Smac and Bax expressions. Furthermore, on day 50, spleen tissues were presented to observe ultrastructural changes in lesions by means of transmission electron microscopy, with fragmentized nucleus, vesiculation of cytoplasm, mitochondria hyperplasia, and increasing lysosomes included. In addition, histopathology results corroborated the toxicity by showing cell hemorrhage, thickening central arteries, and enhanced capsule thickness. To sum up, our study revealed that the combination of Cd and Mo could induce remarkable damage to the spleen of goats by promoting cell apoptosis in the mitochondrial pathway and affecting the deposition of Mo and Cd.

To investigate the effects of molybdenum (Mo) combined with cadmium (Cd) on the antioxidant function and the mRNA expression levels of apoptosis-related genes in duck ovaries, 60 healthy 11-old-day female ducks were treated with hexaammonium molybdate ([(NH4)6Mo7O24·4H2O]) or/and cadmium sulfate (3CdSO4·8H2O) at different doses on a daily basis for 120 days. On the 120th day, ten female birds in each group were euthanized, and the ovaries and blood were collected to determine the antioxidant indexes and the mRNA expression levels of Bak-1, Bcl-2, and caspase-3 in ovaries. In addition, ovary tissues were subjected to histopathological analysis with optical microscope. The total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity decreased significantly (P < 0.01) in treated groups comparing with control while the nitric oxide synthase (NOS) activity increased (P < 0.01) both in ovary tissue and serum. The Bak-1 and caspase-3 expressions were upregulated while the Bcl-2 was downgraded by Mo or/and Cd. Biomolecules were affected in all metal-treated groups, whereas combined-treated animals showed greater effects. What is more, pathological damage in Mo and Cd combination treated groups was more severe. The results from the present study indicated that Mo or/and Cd caused oxidative stress and apoptosis in duck ovaries. Combination of Mo and Cd showed additive or synergistic effect leading to apoptosis and oxidative stress, and the pathway might be the mitochondrial pathway.

Cadmium (Cd) and high dietary intake of molybdenum (Mo) can cause multiple-organ injury in animals, but the co-induced toxicity of Mo and Cd to spleen in ducks is not well understood. The aim of this study was to investigate the co-induced effects of Mo and Cd on the mRNA expression levels of inflammatory cytokines and heat shock proteins (HSPs) in duck spleens. Two hundred forty healthy 11-day-old ducks were randomly divided into six groups and treated with a commercial diet containing Mo or/and Cd. After being treated with Mo or/and Cd for 30, 60, 90, and 120 days, the mRNA expression levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), HSP60, HSP70, and HSP90 were examined in duck spleens. Histopathology was examined in duck spleens at 120 days. The results indicated that the mRNA expression levels of HSPs were significantly upregulated in the co-induced groups (P < 0.01), while these decreased in the high dietary intake of Mo combined with Cd group at 120 days. Exposure to Mo or/and Cd upregulated the mRNA expression levels of NF-κB, COX-2, and TNF-α in the combination groups (P < 0.01). Furthermore, severe congestion, bleeding, splenic corpuscle structure fuzzy, wall thickness of sheath artery thickening, and oxyhematin were observed in the spleens of combination groups. Meanwhile, the organizational structure damage of the combined groups was more severe than that of the other groups. These results suggested that exposure to Mo or/and Cd might lead to tissue damage, and high expression of HSPs and inflammatory cytokines may play a role in the resistance of spleen toxicity induced by Mo or/and Cd. Interaction of Mo and Cd may have a synergistic effect on spleen toxicity.

Molybdenum (Mo) is an essential trace element for animals and humans. However, the high dietary intake of Mo leads to disease conditions in heavy metal pollution areas. To the best of our knowledge, the effect of high levels of Mo on the apoptosis of hepatocyte in goats has not been investigated. Therefore, the aim of the present in vivo study was to investigate the impact of Mo on mitochondrial oxidative stress and apoptosis genes in the liver using real-time quantitative polymerase chain reaction (RT-qPCR) and transmission electron microscopy, respectively. Thirty-six healthy goats were randomly divided into three groups: two groups treated with ammonium molybdate [(NH4)6·Mo7O24·H2O] at 15 and 45 mg Mo kg(-1) BW, respectively, and a control group without treatment. Liver samples were collected from individual goats at different time intervals. The levels of oxidative stress in the mitochondrial membrane and expression of liver-related apoptosis genes, including Bcl-2, Cyt c, caspase-3, and Smac, were examined. The results demonstrated that the levels of superoxide dismutase (SOD) and catalase (CAT) expression were significantly down-regulated in liver cells, whereas malondialdehyde (MDA), nitric oxide (NO), and total nitric oxide synthase (T-NOS) expression was up-regulated (P < 0.01). The expression of Smac, Cyt c, and caspase-3 was significantly up-regulated, whereas Bcl-2 expression was down-regulated in liver cells (P < 0.01). In addition, histopathological examination revealed varying degrees of vacuolization, irregularity, nuclear fission, and mitochondrial swelling and high-density electrons in the cytoplasm of hepatocytes in groups treated with 15 and 45 mg Mo kg(-1) BW. Thus, these results suggested that high molybdenum induced hepatocyte apoptosis and might involve a mitochondrial pathway.

To investigate the chronic toxicity of molybdenum (Mo) and cadmium (Cd) on the trace elements and the mRNA expression levels of ceruloplasmin (CP) and metallothionein (MT) in duck testicles, 120 healthy 11-day-old male ducks were randomly divided into six groups with 20 ducks in each group. Ducks were treated with the diet containing different dosages of Mo or Cd. The source of Mo and Cd was hexaammonium molybdate ([(NH4)6Mo7O24·4H2O]) and cadmium sulfate (3CdSO4·8H2O), respectively, in this study. After being treated for 60 and 120 days, ten male birds in each group were randomly selected and euthanized and then testicles were aseptically collected for determining the mRNA expression levels of MT and CP, antioxidant indexes, and contents of trace elements in the testicle. In addition, testicle tissues at 120 days were subjected to histopathological analysis with the optical microscope. The results showed that co-exposure to Mo and Cd resulted in an increase in malondialdehyde (MDA) level while decrease in xanthine oxidase (XOD) and catalase (CAT) activities. The mRNA expression level of MT gene was upregulated while CP was decreased in combination groups. Contents of Mo, copper (Cu), iron (Fe), and zinc (Zn) decreased in combined groups while Cd increased in Cd and combined groups at 120 days. Furthermore, severe congestion, low sperm count, and malformation were observed in low dietary of Mo combined with Cd group and high dietary of Mo combined with Cd group. Our results suggested that Mo and Cd might aggravate testicular degeneration synergistically through altering the mRNA expression levels of MT and CP, increasing lipid peroxidation through inhibiting related enzyme activities and disturbing homeostasis of trace elements in testicles. Interaction of Mo and Cd may have a synergistic effect on the testicular toxicity.

Molybdenum (Mo) is an essential element for human beings and animals; however, high dietary intake of Mo can lead to adverse reactions. Cadmium (Cd) is harmful to health. To investigate the toxicity of Mo combined with Cd in duck kidneys, 240 ducks were randomly divided into six groups and treated with a commercial diet containing Mo, Cd or Mo combined with Cd. Kidneys were collected on days 30, 60, 90 and 120 for determining the expression of heat shock proteins (HSPs), including HSP60, HSP70 and HSP90 in the kidney through quantitative RT-PCR. We also determined the antioxidant activity indexes in the kidney mitochondria. Moreover, kidney tissues at 120 days were subjected to histopathological analysis with the optical microscope. The results indicated that the expression of HSPs was highly significantly (P < 0.01) upregulated in the kidneys of the combination groups and the Cd group. Exposure to Cd and a high dose of Mo decreased the total antioxidative capacity and the activity of xanthine oxidase, while malondialdehyde levels and the activity of nitric oxide synthase increased compared with those of the control groups in the kidney mitochondria. This was particularly evident at 90 and 120 days. Histopathological lesions included congestion and bleeding in the renal interstitium, swelling of the distal convoluted tubule epithelial cells, granular degeneration and blister degeneration in the renal tubular epithelial cells. These results suggest that a combination of Mo and Cd leads to greater tissue damage and has a synergistic effect on kidney damage. Oxidative damage of kidney mitochondria may be a potential nephrotoxicity mechanism of molybdenum and cadmium, and the high expression of HSPs may play a role in the resistance of kidney toxicity induced by Mo and Cd.