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Clinical efficiency and safety of Hsp90 inhibitor Novobiocin in avian tibial dyschondroplasia

Author:
Nabi, Fazul, Iqbal, Muhammad K., Zhang, Hui, Rehman, Mujeeb Ur, Shahzad, Muhammad, Huang, Shucheng, Han, Zhaoqing, Mehmood, Khalid, Ahmed, Nisar, Chachar, Bahram, Arain, Muhammad A., Li, Jiakui
Source:
Journal of veterinary pharmacology and therapeutics 2018 v.41 no.6 pp. 902-911
ISSN:
0140-7783
Subject:
Western blotting, angiogenesis, antioxidant activity, biomarkers, blood serum, blood vessels, broiler chickens, cartilage, chicks, chondrocytes, dyschondroplasia, gene expression regulation, genes, growth plate, immunohistochemistry, lameness, medicinal plants, novobiocin, pathogenesis, protective effect, protein content, proteoglycans, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction, thiram, tibia, toxicity
Abstract:
Tibial dyschondroplasia (TD) is a bone defect of broilers and other poultry birds that disturbs growth plate and it causes lameness. Previously we evaluated differential expression of multiple genes involved in growth plate angiogenesis and reported the safety and efficacious of medicinal plant root extracted for controlling TD. In this study, clinical and protective effect of an antibiotic Novobiocin (Hsp90 inhibitor) and expression of Hsp90 and proteoglycan aggrecan was examined. The chicks were divided into three groups; Control, thiram‐induced TD, and Novobiocin injected TD. After the induction of TD, the Novobiocin was administered through intraperitoneal route to TD‐affected birds until the end of the experiment. The expressions and localization of Hsp90 were evaluated by qRT‐PCR, immunohistochemistry (IHC) and western blot, respectively. Morphological, histological examinations, and serum biomarker levels were evaluated to assess specificity and protective effects of Novobiocin. The results showed that TD causing retarded growth, enlarged growth plate, distended chondrocytes, irregular columns of cells, decreased antioxidant capacity, reduced protein levels of proteoglycan aggrecan, and upregulated in Hsp90 expression (p < 0.05) in dyschondroplastic birds as compared with control. Novobiocin treatment restored growth plate morphology, reducing width, stimulated chondrocyte differentiation, sprouting blood vessels, corrected oxidative imbalance, decreased Hsp90 expressions and increased aggrecan level. Novobiocin treatment controlled lameness and improved growth in broiler chicken induced by thiram. In conclusion, the accumulation of the cartilage and up‐regulated Hsp90 are associated with TD pathogenesis and irregular chondrocyte morphology in TD is along with reduced aggrecan levels in the growth plate. Our results indicate that Novobiocin treatment has potential to reduce TD by controlling the expression of Hsp90 in addition to improve growth and hepatic toxicity in broiler chicken.
Agid:
6198190