Gokhan Cuce

Objective: The cyclophosphamide (CP)-related nephrotoxicity may impede cancer treatment. This study investigated the efficacy of geraniol (Ge) at two doses against CP nephrotoxicity. Methods: Fourty-two Wistar albino rats were allocated into six groups (n=7 each group): Group I, control; Group II, CP; Group III, CP+Ge 100 mg/kg; Group IV, CP+Ge 200 mg/kg; Group V, Ge 100 mg/kg; and Group VI, Ge 200 mg/kg. At the end of study, alterations in renal tissues were evaluated using hematoxylin-eosin and histopathological scores were determined. Masson’s trichrome and Periodic acid–Schiff (PAS) staining were also performed for evaluation of fibrosis, parietal layer of Bowman capsule, and Bowman’s space. Immunofluorescence analysis assessed oxidative stress and apoptosis. Consequently, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), caspase 3, and caspase 9 were evaluated. Results: CP caused the histopathological changes, including tubular damage, glomerular degeneration, interstitial inflammation. Ge restored the increased histopathological scores, parietal layer of Bowman capsule, and Bowman’s space caused by CP without dose dependence (P<0.001 for both dose). CP decreased the expression of Nrf-2, while Ge improved this disturbance with greater efficacy at a higher dose (P<0.001 for all). CP exposure increased both caspase 3 and caspase 9 (P<0.001 for both). Ge decreased the expressions of caspase 3 and caspase 9 at two doses (P<0.001 for all). In addition, Ge was more effective in repairing caspase 3 at a higher dose (P=0.006). Conclusion: Ge seems to effectively reverse CP-induced nephrotoxicity. The histopathological improvements are mediated by mechanisms involving the attenuation of oxidative stress and apoptosis. The efficacy of Ge is also dose-dependent.

Diabetes mellitus (DM) is associated with vascular complications that increase morbidity and mortality. Natural antioxidants play a vital role in reducing diabetes-related damage. This study investigated the protective effects of the phenolic monoterpene carvacrol (CAR) against diabetic complications. Thirty-two male Wistar Albino rats (4 months, 250–300 g) were divided into four groups: control, DM, DM + DMSO, and DM + CAR. Type 1 diabetes was induced via intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The DM + CAR group received 20 mg/kg CAR daily for four weeks. Body weight and blood glucose levels were regularly monitored. At the end of the study, aortic tissues were examined using hematoxylin–eosin (H&E), Verhoeff–Van Gieson, and immunohistochemical staining, while cardiac tissues were analyzed with H&E and Masson’s trichrome. Serum levels of ischemia-modified albumin (IMA), cholesterol (CHOL), triglycerides (TG), and high-density lipoprotein (HDL) were measured. In the DM group, IMA and CHOL levels were increased (p = 0.0208 and p = 0.0207, respectively), apoptosis was elevated (caspase-3 expression, p = 0.0001), and marked tissue damage was observed. In contrast, in the DM + CAR group, IMA levels (p = 0.0228) and caspase-3 expression (p = 0.0457) were reduced, and notable improvements were detected in vascular and cardiac tissues. These results suggest that CAR protects against diabetic complications by modulating oxidative stress, inhibiting apoptosis, and preventing tissue injury.

Drug-induced hepatotoxicity is a significant impediment to the use of doxorubicin, a commonly employed chemotherapeutic agent with established efficacy in cancer treatment. The present study aimed to determine the potential protective effects of agomelatine against doxorubicin hepatotoxicity in rat toxicity models. Thirty-two rats were divided into four groups: control (with saline administration), Doxo (with 40 mg/kg doxorubicin administration), Doxo + Ago20, and Doxo + Ago40 (with 20 and 40 mg/kg agomelatine administration and 40 mg/kg doxorubicin administration). On the day of 14 rats were sacrificed, samples were collected for comparison of immunohistochemical, hematological, and biochemical analysis. There were statistically significant differences between the study groups in terms of immunohistochemical, hematological, and biochemical parameters. Agomelatine administration reduced the TNF-alpha, and caspase-3, which increased by doxorubicin, and reversed levels of oxidative stress markers altered by doxorubicin (p < 0.05). Doxorubicin induces oxidative stress, apoptosis, and hepatotoxicity. Agomelatine may be favored as a primary antidepressant to mitigate hepatic damage induced by doxorubicin.

Objective: Hypothyroidism is a problem of deficient production of thyroid hormones. These hormones regulate metabolism. Therefore, the current health status of the person is adversely affected due to thyroid hormone deficiency. Coenzyme Q10 (CoQ10) is a vitamin-like substance with strong antioxidant properties. The aim of this scientific study is to investigate the effects of CoQ10 on hypothyroidism at sera level with important biomarkers glial cell line-derived neurotrophic factor (GDNF), promyelocytic leukaemia zinc finger protein (PLZF), high mobility group box transcription factor 3 (SOX3) and thymocyte differentiation antigen 1 (THY1). Material and Methods: Four experimental animal groups were formed: Control group (n:7); hypothyroidism group (n:7); CoQ10 group (n:7); hypothyroidism + CoQ10 group (n:7). On the thirty-first day, sera of the animals were collected and Gdnf, Plzf, Sox3, Thy1 expression levels were analyzed in the blood. Results: Significant results occurred in all four biomarkers. As a final result, both hypothyroid pathology was associated with all biomarkers, and CoQ10 positively affected hypothyroidism. Conclusion: The effect of coenzyme Q10 on gene expression levels of Plzf, Gdnf, Thy1, Sox3 at sera level in rats with experimental hypothyroidism was shown by molecular analyses. Coenzyme Q10 regulates sera gene expression levels during treatment.

Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 mu g), kisspeptin + astressin 2B (1 mu g), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.

Aim: This study aimed to evaluate the effects of tocilizumab (TCZ), a recombinant humanized, anti-human monoclonal antibody of the immunoglobulin G1k subclass, on vascular morphological changes, endothelial apoptosis, and the levels of pro-inflammatory and apoptotic cytokines, such as IL-6, tumor necrosis factor-alpha (TNF-α), caspase-3, Bcl-2 associated X-protein (BAX), and vascular endothelial growth factor (VEGF) in a rat SAH model. Material and Method: The rats were randomly assigned (animal study) to 4 groups KONÜDAM Experimental Animal Research Center, Necmettin Erbakan University, Meram Faculty of Medicine, Konya, Turkey; 15/03/2019): (1) normal control (without SAH); (2) SAH (without treatment); (3) SAH treated with saline (SAH + Sal.); and (4) SAH treated with TCZ (SAH + Toc.). The tissues were measured using enzyme-linked immunosorbent assay (ELISA) kits. A series of brain and basilar artery sections were categorized into several subgroups for hematoxylin and eosin (H&E) staining, immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Results: The levels of caspase, BAX, and IL-6 in the SAH + TOC group were significantly lower than in other groups. TCZ treatment significantly increased the lumen of the basilar artery compared with that in the SAH and SAH + SAL groups without treatment (p=0.002 and p=0.004 respectively). SAH increased the apoptotic index in the endothelium compared with TCZ treatment (p=0.027) groups. Conclusion: It can be concluded that TCZ is safe and effective for treating experimental SAH. The results reveal clearly experimental evidence for the potential clinical application of TCZ in SAH patients.

Endometrial cancer is the most common type of cancer in the female reproductive system. Geraniol is acyclic monoterpene alcohol derived from essential oils of aromatic plants. This study aimed to investigate the apoptosis pathway of geraniol on Ishikawa cells. The cytotoxic effects of Geraniol on Ishikawa cells were determined by an MTT test. Ishikawa cells were seeded on cover slips, the IC50 dose was applied, and the cells were incubated with antibodies against Bax, Bcl-2, and TUNEL Assay. mRNA expression analysis of apoptosis-related genes was determined by RT-qPCR with an IC50 dose of Geraniol. The IC50 dose of Geraniol decreased Bcl-2 staining significantly, but it significantly increased Bax staining and TUNEL positive cells. A significant increase in the Bax, caspase3, caspase-8, cytochrome C and Fas genes and a significant decrease in the Bcl-2 gene was observed when the IC50 dose group was compared to the cells in the control group based on their mRNA expression levels.Analysis of expression of genes whose products are involved in apoptosis suggests the involvement of the mitochondrial pathway.

We investigated the effects of Nigella sativa oil on ovary volume, nuclear factor-kappaB (NF-κB), X-linked inhibitor of apoptosis protein (XIAP) expression, and serum malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS) and total oxidant status (TOS) levels in diabetic rats. We divided 21 adult female rats into three groups: controls, diabetics and diabetics + N. sativa oil. The diabetics + N. sativa oil group was given 0.2 mg/kg/day N. sativa oil 6 days/week for 4 weeks. NF-κB and XIAP expression was assessed in ovarian sections using immunohistochemistry. The right and left ovary volumes were calculated using stereology. We also measured serum MDA, SOD, TAS and TOS levels. We found that N. sativa oil reduced hyperglycemia, but not to control levels. N. sativa oil also exhibited antioxidant properties as demonstrated by reduced serum TOS and MDA levels, and increased SOD and TAS levels compared to controls. We found no significant difference in total ovarian volume, XIAP or NF-κB expression among the groups, which may be due to the short study period. Our findings suggest that N. sativa oil may be useful for reducing blood glucose levels and elevated oxidant activity in diabetic patients.

Monocrotaline (MCT) is a hepatotoxic pyrrolizidine alkaloid that is derived from plants; exposure may occur by consumption of contaminated grains, herbal teas and medicines. MCT can cause liver damage. We investigated the antioxidant effects of selenium (Se) and vitamin E against the toxic effects of MCT. Female Wistar albino rats were divided into four groups: a control group, an MCT group, an MCT + Se group, and an MCT + vitamin E group. Liver tissues were harvested, fixed, processed to paraffin and sections were cut. Anti-von Willebrand factor (vWF) immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL), and hematoxylin and eosin staining were performed. Serum and liver tissue glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx) levels were measured. Histopathological and TUNEL data showed significantly increased liver damage in the MCT group compared to controls. Histopathological and TUNEL staining indicated significant improvements in the MCT + vitamin E and MCT + Se groups compared to the MCT group. MCT significantly reduced the serum GSH level and GPx activity, and liver GPx activity. Biochemical data indicated a significant improvement in serum GSH level in the MCT + vitamin E group compared to the MCT group. We suggest that vitamin E and Se afford limited protection against MCT hepatotoxicity.