The aim of this study was to investigate the possible protective role of sodium selenite on aflatoxin B₁-induced oxidative stress and apoptosis in spleen of broilers. Two hundred one-day-old male broilers, divided into five groups, were fed with basal diet (control group), 0.3 mg/kg AFB₁ (AFB₁ group), 0.3 mg/kg AFB₁ + 0.2 mg/kg Se (+Se group I), 0.3 mg/kg AFB₁ + 0.4 mg/kg Se (+Se group II) and 0.3 mg/kg AFB₁ + 0.6 mg/kg Se (+Se group III), respectively. According to biochemical assays, AFB₁ significantly decreased the activities of glutathione peroxidase, total superoxide dismutase, glutathione reductase, catalase and the level of glutathione hormone, while it increased the level of malondialdehyde. Moreover, AFB₁ increased the percentage of apoptosis cells by flow cytometry and the occurrence of apoptotic cells by TUNEL assay. Simultaneous supplementation with sodium selenite restored these parameters to be close to those in control group. In conclusion, sodium selenite exhibited protective effects on AFB₁-induced splenic toxicity in broilers by inhibiting oxidative stress and excessive apoptosis.

Hepatic oxidative stress, as one important mechanism of cadmium (Cd)-induced hepatic toxicity, could, as known, be ameliorated by vitamin E (VE). However, the underlying mechanism remains to be elucidated. To investigate whether the antioxidant vitamin E can protect against Cd-induced sub-chronic liver injury associated with oxidative stress and nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway, male Sprague-Dawley rats (nine-week-old) were randomly divided into four groups (eight rats/group), namely, control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl₂) and VE+Cd (100 mg/kg VE+5 mg/kg CdCl₂), and received intragastric administration of Cd and/or VE for four weeks. Cd-exposure alone resulted in reduced liver weight, liver histological alteration and oxidative stress, accumulation of Cd in the liver, elevated ALT and AST concentrations in serum together with decreased mRNA and protein expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO-1, GCLC, GCLM and GST). However, the co-treatment of Cd and VE significantly ameliorated the changes mentioned above, and promoted the expression of genes and proteins of Nrf2 pathway related molecules in comparison to the Cd-exposure alone. Our results indicate that the protective effect of VE against Cd-induced sub-chronic hepatic damage in rats is associated with the inhibition of oxidative stress and activation of Nrf2 pathway.

Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, and Bcl-2 family proteins induced by nickel chloride (NiCl₂) in the kidneys of broiler chickens, using flow cytometry, terminal deoxynucleotidyl transferase 2ʹ-deoxyuridine 5ʹ-triphosphate dUTP nick end-labeling (TUNEL), immunohistochemstry and quantitative real-time polymerase chain reaction (qRT-PCR). We found that dietary NiCl₂ in excess of 300 mg/kg resulted in a significant increase in apoptosis, which was associated with decrease in MMP, and increase in apoptosis inducing factor (AIF) and endonuclease G (EndoG) protein and mRNA expression. Concurrently, NiCl₂ inhibited the PI3K/Akt pathway, which was characterized by decreasing PI3K, Akt1 and Akt2 mRNA expression levels. NiCl₂ also reduced the protein and mRNA expression of anti-apoptotic Bcl-2 and Bcl-xL and increased the protein and mRNA expression of pro-apoptotic Bax and Bak. These results show that NiCl₂ causes mitochondrial-mediated apoptosis by disruption of MMP and increased expression of AIF and EndoG mRNA and protein, and that the underlying mechanism of MMP loss involves the Bcl-2 family proteins modulation and PI3K/Akt pathway inhibition.

Aflatoxin B₁ (AFB₁), which causes hepatocellular carcinoma and immune-suppression, is commonly found in feedstuffs. To evaluate the ability of selenium (Se) to counteract the deleterious effects of AFB₁, two hundred 1-day-old male avian broilers, divided into five groups, were fed with basal diet (control group), 0.3 mg/kg AFB₁ (AFB₁ group), 0.3 mg/kg AFB₁+0.2 mg/kg Se (+Se group I), 0.3 mg/kg AFB₁+0.4 mg/kg Se (+Se group II) and 0.3 mg/kg AFB₁+0.6 mg/kg Se (+Se group III), respectively. Compared with control group, the relative weight of spleen in the AFB₁ group was decreased at 21 days of age. The relative weight of spleen in the three +Se groups was higher than that in the AFB₁ group. By pathological observation, the major spleen lesions included congestion in red pulp and vacuoles appeared in the lymphatic nodules and periarterial lymphatic sheath in the AFB₁ group. In +Se groups II and III, the incidence of major splenic lesions was decreased. The percentages of CD₃⁺, CD₃⁺CD₄⁺ and CD₃⁺CD₈⁺ T cells in the AFB₁ group were lower than those in control group from 7 to 21 days of age, while there was a marked increase in the three +Se groups compared to the AFB₁ group. The results indicated that sodium selenite could improve the cellular immune function impaired by AFB₁ through increasing the relative weight of spleen and percentages of splenic T cell subsets, and alleviating histopathological spleen damage.

To explore AFB₁-induced damage of the small intestine, the changes in structure and expression of TLRs (Toll-like Receptors) in the small intestine of chickens were systematically investigated. Ninety healthy neonatal Cobb chickens were randomized into a control group (0 mg/kg AFB₁) and an AFB₁ group (0.6 mg/kg AFB₁). The crypt depth of the small intestine in the AFB₁ group was significantly increased in comparison to the control chickens, while the villus height and area were evidently decreased, as well as the villus:crypt ratio and epithelial thickness. The histopathological observations showed that the villi of the small intestine exposed to AFB₁ were obviously shedding. Based on ultrastructural observation, the absorptive cells of small intestine in the AFB₁ group exhibited fewer microvilli, mitochondrial vacuolation and the disappearance of mitochondrial cristae, and junctional complexes as well as terminal web. Moreover, the number of goblet cells in the small intestine in the AFB₁ group significantly decreased. Also, AFB₁ evidently decreased the mRNA expression of TLR2-2, TLR4, and TLR7 in the small intestine. Taken together, our study indicated that dietary 0.6 mg/kg AFB₁ could induce histopathological injuries and ultrastructural changes, and depress levels of TLR mRNA in the chicken small intestine.

Background: Obesity is a globally increasing health problem that impacts multiple organ systems and a potentially modifiable risk factor for many diseases. Obesity has a significant impact on lung function and is strongly linked to the pathophysiology that contributes to lung diseases. On the other hand, reports have emerged that obesity is associated with a better prognosis than for normal weight individuals in some lung diseases, including pneumonia, acute lung injury/acute respiratory distress syndrome, chronic obstructive pulmonary disease, and lung cancer. The lesser mortality and better prognosis in patients with obesity is known as obesity paradox. While obesity paradox is both recognized and disputed in epidemiological studies, recent research has suggested possible mechanisms. Summary: In this review, we attempted to explain and summarize these factors and mechanisms, including immune response, pulmonary fibrosis, lung function, microbiota, fat and muscle reserves, which are significantly altered by obesity and may contribute to the obesity paradox in lung diseases. We also discuss contrary literature that attributes the “obesity paradox” to confounding. Key Messages: The review will illustrate the possible role of obesity in the prognosis or course of lung diseases, leading to a better understanding of the obesity paradox and provide hints for further basic and clinical research in lung diseases.