Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine.

Introduction: Zinc (Zn) is an essential trace element in animals, but excessive intake can lead to renal toxicity damage. Thus, the exploration of effective natural antagonists to reduce the toxicity caused by Zn has become a major scientific problem. Methods: Here, we found that hesperidin could effectively alleviate the renal toxicity induced by Zn in pigs by using hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, fluorescence quantitative PCR, and microfloral DNA sequencing. Results: The results showed that hesperidin could effectively attenuate the pathological injury in kidney, and reduce autophagy and apoptosis induced by Zn, which evidenced by the downregulation of LC3, ATG5, Bak1, Bax, Caspase-3 and upregulation of p62 and Bcl2. Additionally, hesperidin could reverse colon injury and the decrease of ZO-1 protein expression. Interestingly, hesperidin restored the intestinal flora structure disturbed by Zn, and significantly reduced the abundance of Tenericutes (phylum level) and Christensenella (genus level). Discussion: Thus, altered intestinal flora and intestinal barrier function constitute the gut-kidney axis, which is involved in hesperidin alleviating Zn-induced nephrotoxicity. Our study provides theoretical basis and practical significance of hesperidin for the prevention and treatment of Zn-induced nephrotoxicity through gut-kidney axis.

Exposure to zinc induces lysosomal-mitochondrial axis-mediated apoptosis in PK-15 cells.

Zinc (Zn), a kind of metallic element, can cause poisonous effects on host physiology when its excess exposure. Lysosomes and mitochondria are the toxic targets of heavy metals, and the lysosomal-mitochondrial axis is also verified to take part in apoptosis, but the related underlying mechanisms in Zn-induced cytotoxicity remain undefined. Here, we identified that excess Zn could cause cell damage in PK-15 cells accompanied by the lysosomal and mitochondrial dysfunction, with the evidence by the elevated levels of cathepsin B/D (CTSB/CTSD) in cytoplasm and decrease of Lyso-Tracker Red signal, red fluorescence intensity of AO staining, mitochondrial complex enzyme activities and ATP production. Additionally, the number of Annexin V+/PI--stained cells, apoptosis-related genes (Bax, Bid, Bak1, Caspase-9, and Caspase-3) and proteins levels of Bax, Bak1, Caspase-9, cleaved Caspase-3 and cytoplasmic Cyt C were signally elevated under Zn exposure, while the protein levels of Bcl2 and mitochondrial Cyt C were observably decreased. Importantly, Pepstatin A (the activity inhibitor of CTSD) and RNA interference of CTSD (si-CTSD) was used to reduce the release of lysosomal CTSD to the cytoplasm, which could signally alleviated Zn-induced mitochondrial damage and apoptosis. In summary, these results suggested that Zn could induced lysosomal and mitochondrial dysfunction in PK-15 cells, and the CTSD played an important role in Zn-induced lysosomal-mitochondrial axis-mediated apoptosis. Our results provided a new insight in Zn-induced toxicology, which for protecting the ecological environment and public health.

Effects of replacement of corn silage and distillers' grain diets with hay during prepartum on the health and production performance of dairy heifers postpartum.

In this study, we aimed to comprehensively evaluate the effects of prepartum replacement of corn silage and distillers' grain diets with hay on the postpartum health and production performance in dairy heifers. Pregnant Holstein dairy heifers were randomly assigned to two groups and fed different diets with the same net energy and protein concentrations. The low corn silage plus hay (CH) group diet mainly contained oat hay (28.5%), corn silage (25%) and folium ginkgo (23%). The high corn silage plus distillers' grains (CD) group diet contained corn silage (53.5%), distillers' grains (5%) and folium ginkgo (18%). Dairy heifers were fed from the beginning of pregnancy to the end of the transition period. Calf birthweight, postpartum morbidity, milk production and reproductive performance were determined. Compared with the cows in the CH group, those in the CD group presented increased calf birthweight and a high risk of some postpartum disorders (p < 0.05), particularly ketosis (37.63% vs. 24.54%) and retained placenta (9.41% vs. 3.92%). However, there was no difference between the groups in reproductive performance, including first timed artificial insemination (TAI) rate, date of TAI and conception rate of TAI. The lactation curves showed no difference in milk yield during the peak lactation period of primiparous cows between the CH and CD groups; the total milk production was 33.39 kg and 33.19 kg respectively. Notably, the time to peak milk production was delayed in the CD group. It can be concluded that replacing corn silage and distillers' grains with hay can reduce postpartum morbidity in dairy heifers and shorten the time to peak milk production.

Case Report: Abomasum Impaction in Beef Cattle Due to High Intake of Distillers' Grain and Treatment Options in Southwest China.

In Southern China, distillers' grain is the main feed ingredient for small beef cattle farms. High intake of distillers' grain may lead to abomasum impaction, a disorder caused by the accumulation of solid content within the organ. For treatment, there are non-surgical and surgical options. In this study, we aimed to describe the clinical presentation, diagnosis, and treatment of beef cattle with abomasum impaction due to high intake of distillers' grain. Forty-nine Simmental beef cattle from 13 farms in Chongqing, China, were diagnosed with abomasum impaction. Animals were male, aged ≤2 years, and weighed between 200 and 350 kg. In this retrospective study, information on distillers' grain intake and clinical data were collected for 49 beef cattle diagnosed with abomasum impaction. The animals were treated between 2011 and 2019 with either non-surgical therapy or surgery. Animals diagnosed with mild abomasum impaction (n = 14) fully recovered after non-surgical treatment. Among moderate cases (n = 19), 12 cattle recovered after non-surgical treatment (63%), while the remaining seven did not respond well and underwent surgery. Three of those animals were subsequently cured (3/7). Among the severe cases (n = 16), four cattle were cured after non-surgical treatment (25%) (4/16). Of the remaining 12 cattle, six were slaughtered, and six died after surgery. Non-surgical treatment is efficient for mild abomasum impaction caused by a high intake of distillers' grain and may be considered for both moderate and severe cases. However, the treatment success rate for more severe cases decreases as the disease severity worsens.