Neonicotinoid insecticides, 30% of insecticides marketed worldwide, have selective toxicity on insects through α4p2 nicotinic acetylcholine receptors. Although it is known that acetamiprid exerts toxicity on several organ systems, its toxic effects on the pancreas and its mechanism of action have not been clarified yet. Therefore, in the present study, the cytotoxic and genotoxic potentials of acetamiprid on the AR42J pancreatic cell line were evaluated. The (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay and comet assay were conducted for the cyto- and genotoxicity evaluations, respectively. Reactive oxygen species (ROS) production was assessed by flow cytometry and glutathione (GSH) levels were determined by ELISA for oxidative damage potential, which is thought to be an underlying mechanism of cyto-/genotoxic effects. To reveal the dose-response relationship the concentration range of 1-6 mM was selected for the assays. Cell viability decreased in a dose-dependent manner and the inhibitory concentration 50 value was calculated as 12.61 mM by the MTT assay. Acetamiprid induced DNA damage in all concentrations tested in a dose-depending manner. The mean tail intensity values were 3.84 and ≤32.96 for the control and exposure groups, respectively. There was no significant difference for ROS production; however, the GSH level was reduced at the highest concentration. It is thought that the present study will contribute to the literature due to the lack of data on the potential toxic effects of acetamiprid on the pancreas. To better understand acetamiprid toxicity, further studies including a wide range of mechanistic parameters are needed.

Acetamiprid (ACE), a commonly used neonicotinoid insecticide, is correlated with neurological symptoms, immunotoxicity and hepatotoxicity. Cellular stress and damage could play an important role in ACE-induced neurotoxicity; however, its mechanism has not been fully understood. We evaluated the effects of ACE on oxidative stress, endoplasmic reticulum (ER) stress, cellular death, mRNA expression levels of related genes and protein expressions of related molecular mechanisms in SH-SY5Y human neuroblastoma cells. The half maximal inhibition of enzyme activity (IC₅₀) value of ACE was determined as 4.26 mM after 24 h of treatment by MTT assay. We revealed an increase in reactive oxygen species (ROS) production and calcium release. Significant increases were measured in inositol-requiring enzyme 1-alpha (IRE1-α) and binding immunoglobulin protein 90 (GRP90) levels as well as mRNA expression levels of caspase 3, 4 and 9 genes indicating enhanced ER stress. Apoptosis and ER stress-related genes were significantly upregulated at ≥2 mM. Indeed, ACE caused apoptosis and necroptosis while necrosis was not observed. There was a significant increase in the protein level of mitogen-activated protein kinase-8 (MAPK8) at 4 mM of ACE while no change was seen for nuclear factor kappa-B (NF-κB) and tumor necrosis factor-alpha (TNF-α). In conclusion, increased cellular stress markers could be proposed as an underlying mechanism of ACE-induced cell death in neural cells.

Background: Grape seed extract (GSE) from Vitis vinifera L. is rich in polyphenols and oligomeric proanthocyanidin complexes (OPCs), and it has shown potential benefits in managing low mood and cognitive function. In this study, we investigated the potential bioactivities of Enovita^®, a standardized GSE extract (GSEe herein) rich in OPCs, in key mechanistic pathways related to low mood conditions and cognitive function. Methods: In vitro assays were conducted to assess GSEe’s inhibitory effects on γ-aminobutyric acid transaminase (GABA-T) and monoamine oxidase A (MAO-A), its binding affinity to the GABA site of GABA-A receptors, and its effects on acetylcholinesterase (AChE). Its neuroprotective effects on human SH-SY5Y neuroblastoma cells under oxidative stress (induced by H₂O₂) were assessed using MTT and LDH release assays. Its antioxidant activities were evaluated using DPPH, ABTS, FRAP, ORAC, HORAC, total phenolic content, and TAS assays. Its cytotoxicity was also evaluated. Results: GSEe showed significant GABA-T inhibitory activity. It also exhibited MAO-A and AChE inhibition, along with moderate binding affinity to the GABA-A receptor. In neuroprotective assays, GSEe provided significant protection to SH-SY5Y cells against oxidative stress. GSEe demonstrated robust antioxidant activity in all assays, including scavenging of DPPH and ABTS radicals, high ferric-reducing power, high polyphenolic contents, and a substantial total antioxidant capacity. Conclusions: GSEe exhibits promising bioactivities, highlighting its potential as a supplement for modulating mood and enhancing cognitive function. Overall, the promising results from these in vitro studies provide a strong foundation for the continued exploration and development of GSEe as a viable natural supplement for enhancing mental health and cognitive function.

Type 2 diabetes (T2DM) is one of the most serious challenges of the 21th century with life-threatening complications and excessive health care costs. In diabetic patients, the main goal in T2DM treatment is the regulation of both blood glucose and lipid levels. For that, Gliclazide (GLZ), an oral antidiabetic, and Atorvastatin (ATV), a lipid lowering agent, are widely used drugs as combination. Diabetes has been reported severe impacts on male reproductive system; however, data obtained about ATV and GLZ treatment alone or in combination are conflicted or insufficient. Herein the effects of ATV and GLZ on male reproductive system in type 2 diabetic male rats have been investigated in the present study. T2DM was induced by high-fat diet and single injection of streptozotocin (STZ) (35 mg/kg) in young adult male Sprague-Dawley rats. The diabetic rats were given ATV (10 mg/kg), GLZ (10 mg/kg) and ATV/GLZ (1:1, 10 mg/kg) combination by oral gavage for 28 days. The hormone levels were determined in the cardiac blood samples; and the histopathological and ultrastructural analyses were conducted in the testicular tissues and epididymal sperms. It was observed that diabetes had severe effects on testicular tissue and spermatogenesis. ATV treatment did not affect sperm count and testes structure (p > 0.05), however ameliorated sperm morphology (p < 0.05). GLZ treatment increased sperm count, and improved sperm morphology, testes structure and spermatogenesis (p < 0.05). ATV/GLZ combination treatment enhanced sperm morphology and improved testicular structure (p < 0.05) while did not affect sperm count (p > 0.05). GLZ treatment regenerated testicular damage and sperm parameters whether alone or in combination with ATV in diabetic rats without affecting hypothalamic-pituitary-gonadal axis.

Paraoxonase 1 (PON1) enzyme plays a major role in antioxidant defense and protects the cells against reactive species. The most common PON1 Q192R and L55M polymorphisms are responsible for a wide variation of PON1 activity, which showed an up to 13-fold interindividual variation among the same genotype. PON1 genotypes were evaluated with the development of pancreatitis, colorectal cancer, and hypothyroidism in a hospital-based, case-control study. Individuals with rs662 G allele had a two-fold risk of developing hypothyroidism. A weak association was found between rs854560 T allele and pancreatitis. The results were preliminary. Further studies with a larger number and detailed biochemical parameters are needed.