Carbofuran cytotoxicity, DNA damage, oxidative stress, and cell death in human umbilical vein endothelial cells: Evidence of vascular toxicity

Abstract

Carbofuran is a broad‐spectrum carbamate insecticide, which principally inhibits the acetylcholinesterase (AChE) enzyme in the nervous system. Nonetheless, their selective action is not restricted to a single species and expanded to humans. No studies are available on the toxicological effects of carbofuran in the endothelial cells (ECs), which first confronts the toxicants in blood vessels. Hence, we have exposed the human umbilical vein ECs (HUVECs) with carbofuran for 24 h, which significantly reduced the cell survival to 25.16% and 33.48% at 500 and 1,000 μM analyzed by MTT assay. In the neutral red uptake (NRU) assay, 16.68%, 30.99%, and 58.11% survival decline was found at 250, 500, and 1,000 μM of carbofuran. HUVECs exposed to carbofuran showed significant increase in the intracellular reactive oxygen species (ROS), indicating oxidative stress at low concentrations. In parallel, HUVECs showed hyperpolarization effects in the mitochondrial membrane potential (ΔΨm) upon carbofuran exposure. Carbofuran induced DNA damage in HUVECs measured as 8.80, 11.82, 35.56, and 79.69 Olive tail moment (OTM) in 100‐, 250‐, 500‐, and 1,000‐μM exposure groups. Flow cytometric analysis showed apoptotic peak (SubG1) and G2M arrest in the HUVECs exposed to carbofuran. Overall, our novel data confirm that carbofuran is toxic for the EC cells, especially at the higher concentrations, which may affect the vascular functions and possibly angiogenesis. Hence, carbofuran should be applied judiciously, and detailed vascular studies are warranted to gain an in‐depth information focusing the transcriptomic and translation changes employing suitable in vivo and in vitro test models.

The Influence of Carbofuran on Purkinje cells death in the fetal cerebellum of mice (Mus Musculus)

“…This can inhibit the normal function of cells and lead to necrosis or cell death [7]. It is important to note that the impact of carbofuran (a toxic substance) on cells depends on the type of toxic substance, dosage, exposure duration, and the type of cells involved [18].…”

Subchronic exposure to Chlorpyrifos, Carbofuran, and Cypermethrin increase sciatic nerve damage and degeneration in adolescent rats

“…Increased ROS, decreased antioxidants, and microtubule damage can be caused by excessive excitation of nerves due to pesticides (Karami-mohajeri & Abdollahi, 2011;Gupta et al, 2007). The three pesticides in this study, namely chlorpyrifos, carbofuran, and cypermethrin, work by inhibiting the action of acetylcholinesterase (AChE) and modulating sodium and calcium channels and then increasing excitation in the nerves (Eaton et al, 2008;Saquib et al, 2021;Kadem Majeed et al, 2014). Increased excitation of nerves leads to dysfunction of mitochondria.…”

The effect of carbofuran administration on protoplasmic astrocyte cell necrosis in the cerebrum of mice (Mus musculus)

“…This can inhibit the normal function of cells and lead to necrosis or cell death [20]. The impact of carbofuran (a toxic substance) on cells depends on the type of toxic substance, its dosage, duration of exposure, and the type of cells involved [18]. Each toxic substance can have different mechanisms of action and different effects on body cells [21].…”