👤 Yavuz Selim Sağlam

Glyphosate (GLY) is a widely used herbicide, particularly in agriculture, and its residues in plants and soil can induce toxic effects in various organisms, including humans, with the brain being especially vulnerable. Eugenol (EU), a natural antioxidant found in cloves, has demonstrated protective effects against different toxic substances. This experimental study explored whether eugenol could mitigate neurological damage triggered by glyphosate exposure in rats. A total of forty male Sprague-Dawley rats were allocated into five experimental groups consisting of control, eugenol (100 mg/kg), glyphosate (150 mg/kg), EU50 combined with glyphosate (50 mg/kg + 150 mg/kg), and EU100 combined with glyphosate (100 mg/kg + 150 mg/kg). Animals received the respective treatments by oral gavage for a period of seven days. Motor and anxiety-related behaviors were evaluated using behaviour tests, after which brain tissues were processed for histopathological analysis. Biochemical analyses included ELISA assessment of oxidative stress markers (MDA, SOD1, GSH, and GPx1), RT-PCR analysis of endoplasmic reticulum (ER) stress- and apoptosis-related genes (GRP78, ATF4, CHOP, PI3K/AKT/mTOR, BAX, and Bcl-2), Western blot evaluation of inflammatory and antioxidant signaling pathways (TLR4/NF-κB and Nrf2/HO-1/SIRT1), and immunohistochemical and immunofluorescence analyses of neuroplasticity, circadian rhythm, and autophagy markers (BDNF, BMAL1, CLOCK, Beclin-1, and LC3A/B). GLY exposure significantly increased lipid peroxidation (MDA), ER stress markers (GRP78 and CHOP), pro-inflammatory mediators (TLR4, NF-κB, TNF-α, and IL-1β), apoptotic signaling (BAX and caspase-3), and autophagy-related proteins, while suppressing antioxidant pathway components. Glyphosate exposure induced behavioral impairments accompanied by increased oxidative stress, inflammatory activation, endoplasmic reticulum stress, apoptosis, and dysregulated autophagy in cerebral cortex tissue. EU treatment dose-dependently attenuated these molecular and histopathological alterations, restored antioxidant and cellular stress responses, and significantly improved behavioral performance, indicating a protective role against GLY-induced neurotoxicity. Overall, EU may represent a promising therapeutic candidate for mitigating herbicide-induced brain injury. Show less

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ β-catenin pathway by binding to β-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the β-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ β-catenin pathway in the pathogenesis of colorectal cancer. Show less