Therapeutic Efficacy And Molecular Mechanism Study Of Osthole And Puerarin Against Thiram-Induced Tibial Dyschondroplasia In Broiler Chickens

Tibial dyschondroplasia(TD)is a skeletal abnormality affecting fast-growing broiler chickens.Apart from causing huge economic losses to the poultry industry worldwide,TD also raises animal welfare concerns.TD is described as a non-vascularized and nonmineralized white opaque mass in the proximal growth plate of the tibia bone.TD affected chickens exhibit poor body condition,deformed tibial bones,and lameness.1.Osthole: A Coumarin Derivative Assuages Thiram-Induced TibialDyschondroplasia by Regulating BMP-2 and RUNX-2 Expressions in ChickensAvian tibial dyschondroplasia affects fast-growing broiler chickens accounting for almost 30% of leg ailments in broilers.The present project was designed to assess the efficacy of osthole against avian tibial dyschondroplasia(TD).Two hundred and forty chickens were equally allocated into control,TD and osthole groups(n = 80).The TD and osthole group chickens were challenged with tetramethylthiuram disulfide(thiram)at 50 mg/kg of feed from 4–7 days,followed by osthole administration at 20 mg/kg orally to the osthole group only from 8–18 days.Thiram feeding resulted in lameness,increased mortality,and decreased production parameters,alkaline phosphatase(ALP),superoxide dismutase(SOD),total antioxidant capacity(T-AOC),and glutathione peroxidase(GSH-PX)levels,along with significantly increased aspartate aminotransferase(AST),alanine aminotransferase(ALT),malondialdehyde(MDA)levels,and growth plate size.Moreover,the genes and protein expressions of BMP-2 and RUNX-2 were significantly down-regulated in TD affected chickens(p < 0.05).Osthole administration showed promising results by alleviating lameness;increased ALP,SOD,T-AOC,and GSH-Px levels;and decreased the AST,ALT,and MDA levels significantly.It restored the size of the growth plate and significantly upregulated the BMP-2 and RUNX-2 expressions(p < 0.05).In conclusion,the oxidative stress and growth plate anomalies could be assuaged using osthole.2.Puerarin enhances vascular proliferation and halt apoptosis in thiram induced avian tibial dyschondroplasia by regulating HIF-1α,TIMP-3 and BCL-2 expressionsTetramethyl thiuram disulfide(thiram)is a dithiocarbamate pesticide used for crop protection and storage.But,it’s widespread utilization is associated with deleterious growth plate cartilage disorder in broilers termed as avian tibial dyschondroplasia(TD).TD results in non-mineralized and less vascularized proximal tibial growth plate cartilage causing lameness and poor growth performance.This study investigated the therapeutic potential of puerarin against thiram toxicity in TD affected chickens.One-day-old broiler chickens(n = 240)were alienated into three equal groups i.e.control,TD and puerarin(n = 80)and were offered standard feed.Additionally,TD and puerarin groups were offered thiram at 50 mg/kg of feed from 4-7 days for TD induction followed by puerarin therapy at 120 mg/kg to puerarin group only from 8-18 days for TD treatment.Thiram feeding to TD and puerarin group chickens caused lameness,mortality,and increased the aspartate aminotransferase(AST),alanine aminotransferase(ALT),malondialdehyde(MDA)levels and growth plate(GP)size and upregulated HIF-1α expression.Besides,the production parameters,alkaline phosphatase(ALP),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)levels and the expressions of TIMP-3 and BCL-2 were decreased(p < 0.05).Puerarin alleviated lameness,enhanced angiogenesis and growth performance and serum and antioxidant enzymes,decreased apoptosis and recuperated GP width by significantly downregulating HIF-1α and upregulating the TIMP-3 and BCL-2 m RNA protein expressions in puerarin group chickens(p < 0.05).In conclusion,the toxic effects associated with thiram can be mitigated using puerarin.