In ovo protective effects of chicoric and rosmarinic acids against Thiacloprid-induced cytotoxicity, oxidative stress, and growth retardation on newly hatched chicks

Thiacloprid (TH) is a neonicotinoid insecticide employed in agriculture to protect fruits and 73 vegetables against different insects. It showed different deleterious effects on the general 74 health of non- target organisms including birds and animals, however, its developmental 75 toxicity has yet to be fully elucidated. Chicoric (CA) and rosmarinic (RA) acids are 76 polyphenolic compounds with a wide range of beneficial biological activities. In this study, 77 the possible protective effects of CA and RA were investigated in chick embryos exposed in 78 ovo to TH (1µg/egg) with or without CA (100 µg/egg) or RA (100 µg/egg) co-exposure. TH 79 reduced the hatchling body weight, body weight/egg weight, and relative weight of bursa of 80 Fabricius in the one-day-old hatchlings. Examination of the 7th-day-old chicks revealed a 81 decline in feed intake, daily weight gain, feed conversion ratio (FCR), and plasma levels of 82 T3, T4, and growth hormone. Serum ALT, AST activities, and total cholesterol levels showed 83 significant elevations. Hepatic MDA was increased with a reduction in SOD activity and 84 GSH level and downregulation of the liver SOD and GST gene expression pattern. Serum 85 IgG and IgM levels were reduced, and various histopathological alterations were noticed in 86 the liver. Co-administration of CA or RA with TH mitigated the toxic effects on hatchlings. 87 When both CA and RA are combined, they present a synergistic protective effect. CA and 88 RA can be used as protective agents against TH toxicity as they improve growth performance 89 and have hepatoprotective and immunostimulant effects in newly hatched chicks.