Articles in Press

Background Mancozeb (MNZ) is known to induce oxidative stress and thyroid dysfunction. Linagliptin (Lina), a DPP-4 inhibitor used in diabetes treatment with antioxidant and anti-inflammatory properties, may offer protection against MNZ-induced thyroid damage. This study aimed to evaluate the protective effects of Lina in combination with MNZ, on thyroid function, oxidative stress markers, and histopathology in rats. Methods and materials Fifty four Wistar rats were randomly divided into six groups and treated for six weeks with oral Lina and/or intraperitoneal MNZ, including appropriate controls. Serum levels of thyroid hormones (T3, T4), TSH, and thyroid tissue oxidative stress markers were quantified using ELISA kits. Histopathological changes, including hyperplasia and hypertrophy, were examined. Data were analyzed by one-way ANOVA followed by Tukey’s post-hoc test (p < 0.05). Results MNZ exposure significantly decreased T3 and T4 levels, increased TSH, elevated malondialdehyde (MDA), and reduced antioxidant enzymes (catalase [CAT], superoxide dismutase [SOD]) and total thiol content. Co-administration of Lina (20 mg/kg) markedly increased antioxidant enzyme activities and total thiol, lowered MDA, improved thyroid hormone profiles, attenuated TSH elevation, and reduced histopathological damage in the thyroid gland. Lower doses of Lina showed limited protective effects. Conclusion MNZ induces oxidative stress and mild thyroid dysfunction in rats, while Lina exerts protective effects by enhancing antioxidant defenses, restoring hormonal balance, and preserving thyroid tissue structure. These findings suggest Lina’s potential as a therapeutic agent to mitigate thyroid damage caused by oxidative stress-related environmental toxins such as MNZ.

Background: Paraoxonase-3 (PON3), a member of the paraoxonase (PON) enzyme family, is located on high-density lipoprotein (HDL) protects against atherosclerosis with its lactonase (LA) activity. This study, the effects of anaerobic training on protein level and LA activity of serum PON3, HDL level and its subgroups’ LA activities (HDLLA, HDL2LA, HDL3LA) as well as the role of PON3 gene A665G polymorphism (PON3P) were investigated. Methods: Male trained athletic group performing anaerobic training (AG: n=36, age=20.56 ± 2.42 years) and the control group (CG: n=39, age=22.26 ± 3.44 years) participated in this study. The protein level and LA activity of serum PON3, HDL and subgroups’ LA activities, oxidative stress index (OSI), oxidized low-density lipoprotein (oxLDL) and the PON3P were determined using blood samples. PON3-A665G groups were categorized as AA, AG and GG phenotype groups. The G-carries (Gc) phenotype group consisted of the AG and GG groups combined. Results: Serum LA, PON3LA activities and PON3 protein level of AG were lower than CG while OSI (including oxLDL) level was higher (p<0.05). HDLLA (p<0.05) and HDL3LA activities and PON3 protein level​​ of control AA group ( CAA) were lower than control G carrier group (CGc) (p<0.01). Serum LA, PON3LA, HDL3LA, HDLPON3LA activities and serum PON3 protein levels of athletic G carrier group (AGc) were significantly lower than control group (p<0.05). Conclusions: Although the Gc genotype is associated with higher PON3 and HDL activity, anaerobic training may reduce this advantage, potentially increasing the risk of atherosclerosis in Gc genotype.

This study investigated the effect of three types of the intensity of aerobic exercise on liver tissue and JNK and ERK genes. In this study, 40 male Wistar rats with a mean age of 2 months and a weight of 250 g were selected. Rats were trained for an 8-week training protocol in aerobic exercise with moderate-intensity training (MIT), high-intensity training (HIT). High-intensity interval training (HIIT) . The rats were anesthetized, blood samples were taken, and liver tissues were extracted. Data were analyzed using SPSS version 22. The expression levels of each gene were calculated by replacing the data obtained by RT-PCR in the 2 -ΔΔct formula. The results showed that there was a significant difference in JNK gene expression between the 8 weeks control group and the MIT, HIT, HIIT exercise groups (P <0.05). HIT and HIIT exercise was observed (P = 0.015, P <0.001, respectively) and gene expression in HIIT was higher than HIT and MIT. The results of this study showed that exercise with more intensity may be more effective in the recovery process if hepatic tissue injury occurs.

Background: Bipolar disorder (BD) is a chronic psychiatric illness involving recurrent shifts between manic and depressive states. This study was designed to examine the potential effects of vanillic acid (VA) on behavioral alterations and oxidative stress parameters in a ketamine (KET)-induced mania model in rats. Methods: Rats were allocated into eight groups, including three saline groups receiving distilled water, lithium chloride or VA (100 mg/kg), and five KET-treated groups receiving distilled water, lithium chloride or VA (25, 50 or 100 mg/kg); lithium and VA were administered orally for 14 days, whereas KET was injected intraperitoneally from days 8 to 15. On day 15, animals underwent Y-maze test and open field test. Levels of malondialdehyde (MDA) and glutathione as well as superoxide dismutase and catalase activities were assessed in the cerebral cortex and hippocampus. Results: KET induced hyperlocomotion, increased rearing, decreased center crossings, impaired working memory and disrupted antioxidant defenses. VA attenuated behavioral abnormalities and improved antioxidant status, showing behavioral effects comparable to lithium. VA exerted more pronounced antioxidant effects in the cerebral cortex, whereas lithium appeared to be more effective in the hippocampus. Lithium and all tested doses of VA significantly reduced cortical MDA levels, although the KET-induced increase in MDA did not reach statistical significance. Conclusion: These findings provide preliminary evidence for the potential role of VA in modulating behavioral and oxidative alterations in this model. Taken together, the observed effects support the need for additional studies examining the therapeutic value of VA in BD.

Background: Arsenic is widely found in the environment, and its toxicity is a significant public health issue worldwide. Syringic acid (SYRA) is a flavonoid compound with anti-inflammatory effects. Given that the effect of SYRA on sodium arsenite (As)-induced nephrotoxicity remains largely unknown, this study aimed to investigate the effect of SYRA on sodium arsenite-induced nephrotoxicity in mice by reducing oxidative stress, inflammation, and nuclear factor kappa B p-65 (NF-κB-p65) expression. Methods: Thirty male mice were split into five groups of six, based on a power analysis. The groups were set up like this: control (3 ml/kg normal saline); SYRA (25 mg/kg, administered via gavage); As (3 mg/kg, administered via gavage); As + SYRA (10 mg/kg, administered via gavage) and As + SYRA (25 mg/kg, administered via gavage). As was administered daily via gavage for a total of 30 days. SYRA was then given by gavage for 7 days, from day 23 to day 30. On the 30th day, the mice were put under anesthesia, and samples of their heart blood and kidney tissue were taken to check biochemical markers, oxidative stress, inflammatory factors, and the expression of NF-κB-p65 protein. Results: Giving SYRA lowered the levels of blood urea nitrogen, creatinine, and uric acid in the blood compared to the As group (P<0.001). In the SYRA group, levels of total thiol, catalase, superoxide dismutase, and glutathione peroxidase were higher compared to the As group (P<0.001). The SYRA group showed lower levels of thiobarbituric acid-reactive substances, nitric oxide, tumor necrosis factor alpha, and NF-κB-p65 protein expression compared to the As group (P<0.001). The histological results backed up these findings. Conclusion: Giving SYRA might help reduce kidney damage caused by As in mice by lowering oxidative stress, inflammation, and the expression of NF-κB-p65 protein.