Abstract The aim of this study is to investigate the effect of metyrosine on ischemia-reperfusion (I/R) induced ovarian injury in rats in terms of biochemistry and histopathology. Rats were divided into: ovarian I/R (OIR), ovarian I/R+50 mg/kg metyrosine (OIRM) and sham (SG) operations. OIRM group received 50 mg/kg metyrosine one hour before the application of the anesthetic agent, OIR and SG group rats received equal amount of distilled water to be used as a solvent orally through cannula. Following the application of the anesthetic agent, ovaries of OIRM and OIR group rats were subjected to ischemia and reperfusion, each of which took two hours. This biochemical experiment findings revealed high levels of malondialdehyde (MDA) and cyclo-oxygenase-2 (COX-2) and low levels of total glutathione (tGSH), superoxide dismutase (SOD) and cyclo-oxygenase-1 (COX-1) in the ovarian tissue of OIR group, with significant histopathological injury. In metyrosine group, MDA and COX-2 levels were lower than the OIR group whereas tGSH, SOD and COX-1 levels were higher, with slighter histopathological injury. Our experimental findings indicate that metyrosine inhibits oxidative and pro-inflammatory damage associated with ovarian I/R in rats. These findings suggest that metyrosine could be useful in the treatment of ovarian injury associated with I/R.

Abstract Exposure to methanol can cause serious consequences such as permanent visual disturbances and death. The heart tissue is highly vulnerable to ATP deficiency. Our study aimed to investigate whether exogenous ATP administration may alleviate methanol-induced ATP deficiency and subsequent oxidative damage in rat heart tissue. A total of 30 rats were divided into equal five groups; Healthy Group (HG), Methotrexate (MXG), Methanol (MeOH), Methotrexate+Methanol (MXM), and Methotrexate+Methanol+ATP (MMA) groups. We inhibited tetrahydrofolate synthesis by methotrexate to induce methanol toxicity. Methotrexate was administered to MXG, MXM, and MMA group animals for seven days with a catheter directly to the stomach at a 0,3 mg/kg dose per day. At the end of this period, % 20 methanol at a dose of 3 g/kg was administered to MeOH, MMA and MXM group animals. Immediately after methanol application, MMA group animals were injected with ATP at a 4 mg/kg dose intraperitoneally. Blood samples and heart tissues were used for biochemical analysis and histopathological examination. Co-exposure to methanol and methotrexate substantially exacerbated cardiac damage, indicating the potent cardiotoxic effects of methanol. However, the administration of exogenous ATP to MMA group animals brought biochemical oxidative damage parameters and histopathological findings closer to HG.

Abstract Ovarian torsion can be defined as the bending of the ovaries on the supporting ligament, disrupting both venous and arterial blood circulation. Insufficient blood flow causes ovarian tissue hypoxia and leads to ischemia. This study aimed to investigate whether tocilizumab has a protective effect on ischemia-reperfusion injury due to ovarian torsion in rats. Eighteen female Wistar albino rats were divided into three equal groups (Sham (SG), ischemia-reperfusion (OIR), and ischemia-reperfusion+tocilizumab (OIRT)). Degeneration, necrosis, vascular dilatation/congestion, interstitial edema, hemorrhage, and polymorphonuclear lymphocyte (PMNL) infiltration scores were significantly different between the groups (p=0.001 for all parameters). Moreover, the OIRT group had a significant improvement in these criteria compared to the OIR group (p<0.05). Additionally, there was a considerable difference between OIRT and OIR groups in the number of primordial, developing, and atretic follicles groups (p<0.05), while there was no difference in the number of corpus luteum (p=0.052). Stress markers or cytokines, such as MDA, tGSH, NF-κB, TNF-α, IL-1β, and IL-6, were significantly different between groups (p<0.05). Furthermore, a significant improvement was found in the measured variables when the OIRT group was compared with the OIR group (p<0.05). Tocilizumab may be an alternative option for treating ischemia-reperfusion injury due to ovarian torsion.

Abstract The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin—the effect we tested against MTX-induced oral mucosal damage—are well known. Objective Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. Methodology In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. Results Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. Conclusion These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

Abstract Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1β, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties.

Abstract Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.

Abstract Purpose: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). Methods: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. Results: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. Conclusion: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.