Puerarin enhance vascular proliferation and halt apoptosis in thiram-induced avian tibial dyschondroplasia by regulating HIF-1α, TIMP-3 and BCL-2 expressions

Ecotoxicol Environ Saf. 2020 Mar 1:190:110126. doi: 10.1016/j.ecoenv.2019.110126. Epub 2020 Jan 7.

Abstract

Tetramethyl 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 to 7 days for TD induction followed by puerarin therapy at 120 mg/kg to puerarin group only from 8 to 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 mRNA and protein expressions in puerarin group chickens (p < 0.05). In conclusion, the toxic effects associated with thiram can be mitigated using puerarin.

Keywords: Chicken; Gene; Oxidative stress; Puerarin; Thiram; Tibial dyschondroplasia.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Chickens / metabolism
  • Fungicides, Industrial / toxicity*
  • Glutathione Peroxidase / metabolism
  • Growth Plate / drug effects
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Isoflavones / pharmacology*
  • Malondialdehyde / metabolism
  • Neovascularization, Pathologic / chemically induced
  • Osteochondrodysplasias / veterinary*
  • Poultry Diseases / drug therapy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Thiram / toxicity*
  • Tibia / drug effects
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism
  • Vasodilator Agents / pharmacology*

Substances

  • Antioxidants
  • Fungicides, Industrial
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Isoflavones
  • Proto-Oncogene Proteins c-bcl-2
  • Tissue Inhibitor of Metalloproteinase-3
  • Vasodilator Agents
  • Thiram
  • Malondialdehyde
  • Glutathione Peroxidase
  • puerarin