Chlorogenic Acid Alleviates Thiram-Induced Tibial Dyschondroplasia by Modulating Caspases, BECN1 Expression and ECM Degradation

Abstract

Chlorogenic acid (CGA) is a widely applied traditional Chinese medicine ingredient which can be used for the treatment of osteoporosis. In this experiment, we investigated the potential therapeutic effect of chlorogenic acid on thiram-induced tibial dyschondroplasia (TD) and explored the underlying mechanisms that have been rarely mentioned by others yet. Performance indicator analysis and tibial parameter analysis showed that CGA exhibited a definite positive effect on thiram-induced TD chickens. In order to further explore the mechanisms underlying the positive actions of CGA, apoptotic, autophagic genes and MMPs involved in matrix mineralization of growth plate were evaluated in this study. The results showed that CGA decreased the expression of pro-apoptotic genes caspases-3 and caspases-9, leading to the reduction of apoptotic cells accumulated in growth plate. In addition, CGA also increased the level of BECN1, an important gene involved in autophagy, which benefits the survival of abnormal cells. Furthermore, CGA also increased the expression of MMP-9, MMP-10, and MMP-13, which can directly affect the ossification of bones. Altogether, these results demonstrate that CGA possesses a positive therapeutic effect on thiram-induced TD via modulating the expression of caspases and BECN1 and regulating the degradation of ECM (extracellular matrix).

Plastrum Testudinis Extract Mitigates Thiram Toxicity in Broilers via Regulating PI3K/AKT Signaling

“…Moreover, chondrocytes with intact nuclei were much greater in PTE bones than the TD bones as in agreement with other studies [43,45,47]. Chicks with TD exhibited scattered dead and anucleate cells, opaque cartilage, abnormal arrangement of bone cells with disintegrated and dissolved nuclei and a higher percentage of extracellular matrix as in accordance with other researchers [43,44]. This is due to the fact that avascularization in tibia, non-calcification, and increased extracellular matrix lead to a decline in angiogenesis that disturbs the nutrient transportation to developing chondrocytes [9,47].…”

“…The PTE administration alleviated the adverse effects of thiram, and increased the angiogenesis which restored the chondrocytes' arrangement, the network of blood vessels and bone trabecular ratio. Moreover, chondrocytes with intact nuclei were much greater in PTE bones than the TD bones as in agreement with other studies [43,45,47]. Chicks with TD exhibited scattered dead and anucleate cells, opaque cartilage, abnormal arrangement of bone cells with disintegrated and dissolved nuclei and a higher percentage of extracellular matrix as in accordance with other researchers [43,44].…”

“…In the present study, it was evident that TD chickens exhibited poor growth performance in terms of reduced body weight and feed intake, weight gain, difficulty in movement and standing as reported in previous studies [43,45]. Conversely, after PTE administration, the chickens in the PTE group became alert and healthy, and performance indices were significantly improved (p < 0.05) on day 18 in comparison with the TD group.…”

“…Production parameters (i.e., total weight of chicks, feed conversion ratio, and daily feed consumed) and mortality were recorded during the research trial. At four different time points (day 7, 10, 14, and 18), humane slaughtering of chickens (n = 20 from each group) was done (pentobarbital at 25 mg/kg was injected before euthanization) [43], and then the tibia bone growth plate (GP) size (measured using digital caliper), TD score (from 0 to 4 according to lesion severeness as per our previous experiment) [44], and tibia parameters (i.e., length, width, and weight were noticed), then, a few tibial bones were deposited at −80 • C for further analyses [44].…”

Effect of Grape Seed Extract on Tibial Dyschondroplasia Incidence, Liver Weight, and Tibial Angiogenesis in Chickens

“…Tibial Dyschondroplasia (TD) is a severe bone metabolic disorder that adversely affects the proximal growth plate (GP) of the tibia and usually occurs in fast growing chicks (Nabi et al, 2016a(Nabi et al, , 2016b. Present study revealed that chicks fed with thiram-feed exhibited higher TD score and GP measurement with tibial inflammation and inability to walk properly as compared to healthy chicks which leads to reduced growth rate, weight gain and liver weight and increased mortality as reported formerly (Zhang et al, 2019). Treatment with GSE remarkably reduced the TD score and inflammation along with diminishing lesions from the GP region.…”