Thiamethoxam induced hepatotoxicity and pro-carcinogenicity in rabbits via motivation of oxidative stress, inflammation, and anti-apoptotic pathway

Abstract

Thiamethoxam (TMX) is a non-mutagenic neonicotinoid insecticide that is widely used to combat different types of insects. The hepatotoxicity and carcinogenicity of TMX have been approved previously in mice but not in rats. However, the TMX-induced hepatotoxic and pro-carcinogenic effects on rabbits remain unclear. The present study elucidated the roles of oxidative stress, pro-inflammatory cytokines, and apoptosis-related genes in the hepatotoxic and carcinogenic effects of TMX on rabbits. Sixteen male rabbits were equally divided into two groups; eight rabbits orally treated with TMX at a dose of 250 mg/kg b.w for 90 successive days. Hepatotoxic effects of TMX were evidenced by attenuation of liver enzyme activities, elevation of bilirubin levels, and alterations in the hepatic architecture, including hepatocyte death by necrosis and apoptosis, lymphocyte infiltration and fibrosis. TMX induced oxidative stress, as evidenced by the significant increases in malondialdehyde levels and antioxidant enzyme (glutathione transferase and catalase) activities along with a decrease in glutathione levels. TMX also up-regulated the mRNA levels of interleukin-6 (1.6-fold) and B cell lymphoma-2 (1.8-fold) and down-regulated the mRNA level of the tumor necrosis factor-α (0.8-fold), indicating its effects on cell survival and proliferation through the inhibition of apoptosis. Interestingly, the elevated level of carcinoembryonic antigen and the appearance of ground glass-like hepatocytes suggested that TMX exerted a pro-carcinogenic effect. In conclusion, TMX exerts potentially hepatotoxic and pro-carcinogenic effects on rabbits by modulating oxidative/antioxidative status and pro-inflammatory cytokine production, inhibiting apoptosis and activating cell survival pathways.

Moringa Oleifera Leaf Extract Repairs the Oxidative Misbalance following Sub-Chronic Exposure to Sodium Fluoride in Nile Tilapia Oreochromis niloticus

“…In fish, oxidative stress can be defined as an imbalance between oxidants and antioxidant defences [51]. Excessive production of ROS is associated with severe reactions, such as damage of cellular proteins, lipids, and nucleic acid [52]. In addition, ROS can initiate the lipoperoxidation, which is a self-propagating process that leads to formation of peroxyl radical due to the reaction of ROS with the hydrogen atom from an intact lipid [52].…”

Garlic Alleviates the Injurious Impact of Cyclosporine-A in Male Rats through Modulation of Fibrogenic and Steroidogenic Genes

“…ALT and AST are known indicators of hepatic damage, and the ALP concentration is related to hepatocyte function [ 58 ]. The significant elevation of the serum levels of hepatic enzymes AST, ALT, and ALP in the CsA-treated groups in the present study may be due to the rapid release of these enzymes from the cytoplasm into the blood following plasma membrane rupture and parenchymal cellular damage [ 59 , 60 ]. High concentrations of serum transaminases are considered injurious to the liver [ 61 ].…”

Impacts of Enriching Growing Rabbit Diets with Chlorella vulgaris Microalgae on Growth, Blood Variables, Carcass Traits, Immunological and Antioxidant Indices

“…However, there is global increasing attention paid to the screening and production of alternative natural antioxidants or anticancer agents from microalgae [5,32]. The respective response of the CLV on immunity response (IgM and IgG activities) in growing rabbit plasma suggests an improvement in the antioxidant defense system, as well as a further reduction in MDA, which represents the lipid peroxidation [33,34,35,36]. This shows the beneficial health implications of CLV.…”