Sinapic Acid Attenuated Cisplatin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Inflammation with GPX4-Mediated NF-kB Modulation.

The use of cisplatin is severely limited by the risk of developing cardiovascular complications. Sinapic acid may reduce cisplatin's side effects. The anti oxidant, anti-inflammatory, and peroxynitrite-scavenging properties of sinapic acid could provide protection against the cardiotoxicity caused by cisplatin. To induce toxicity in rats, cisplatin was administered for a period of 5 weeks. Animal electrocardiograms were obtained after cisplatin toxicity had taken effect. Blood samples and heart tissues were then harvested from the anesthetized animals. The ELISA technique was used to evaluate the level of proinflammatory cytokines and oxidative and nitrosative stress indicators in the heart tissue and serum. A real-time PCR was used to analyze GPX4 and NF-κB expression in the heart tissue. Hematoxylin-eosin and Masson's trichrome were also utilized. Electrocardiograms data showed an increase in QRS and QT intervals. Biochemically, cisplatin increased oxidative, nitrosative, and proinflammatory cytokine levels. Animals exposed to cisplatin had histopathological findings in the heart tissue, according to the results of histological assessment. Sinapic acid reduced TNF-alpha, interleukin-6, malondialdehyde, and ischemia-modified albumin. Sinapic acid also reduced oxidative and nitrosative stress. Furthermore, Sinapic acid restored lengthy QT and QRS. Cisplatin-treated rats had higher NF-κB activation than controls. This effect was successfully inhibited by sinapic acid. Histopathologically, tissues treated with sinapic acid were less damaged than tissues treated with cisplatin. In conclusion, our results suggest that sinapic acid exhibited a protective effect against the cardiotoxicity induced by cisplatin. These effects may be caused by the overexpression of GPX4 and the downregulation of NF-KB, as well as antioxidant and anti-inflammatory properties.

Boric acid improves the behavioral, electrophysiological and histological parameters of cisplatin-induced peripheral neuropathy in rats.

Boric acid (BA) has been used in many diseases because it increases the amount of reduced glutathione in the body and reduces oxidative damage. This study aims to investigate the effects of boric acid in cisplatin-induced neuropathy, in which oxidative stress is also effective in its pathophysiology. In this study, 8-10 weeks old, 170-190 g Wistar Albino rats were used. Each group contained seven rats (n = 35). Experimental groups consist of control, sham, neuropathy, treatment, and boric acid groups. For the neuropathy model, a single dose of cisplatin (3 mg/kg, i.p) was administered once a week for five weeks, and for the treatment group, boric acid was administered daily (100 mg/kg, intragastric) for five weeks. After drug administration, the rotarod test to evaluate motor performance, the tail-flick and hot/cold plate tests to evaluate sensory conduction states, the von Frey filament test to evaluate the mechanical allodynia, and the adhesive removal test to assess sensorimotor function were performed. The sciatic nerve's motoric conduction velocity was also assessed electrophysiologically. Oxidative stress parameters were also assessed biochemically in sciatic nerve tissue and serum. Hematoxylin and eosin staining was used to evaluate the sciatic nerve tissue histopathologically. The motor conduction velocity of the sciatic nerve, impaired by cisplatin, was increased considerably by boric acid (p < 0.05). It also reduced the latency time of the compound muscle action potential (CMAP), which was increased by cisplatin. (p < 0.05). The von Frey filament test results demonstrated increased pain sensitivity of the cisplatin group increased, and mechanical allodynia was observed. Boric acid significantly alleviated this condition (p < 0.05). In the cold plate, adhesive removal, and rotarod tests, boric acid attenuated the adverse effects of cisplatin (p < 0.05). Biochemically, BA reduced the level of MDA, which was raised by cisplatin, and significantly increased the level of SOD, which was lowered by cisplatin (p < 0.05). Histopathologically; BA reduced neuronal degeneration and vacuolization caused by cisplatin. As a consequence, it has been determined that boric acid alleviates the adverse effects of cisplatin. BA reduced the destructive effect of cisplatin by reducing oxidative stress, and this effect was verified electrophysiologically, behaviorally, and histopathologically.

Comparison of the StaRRsed Interliner device with Westergren method in erythrocyte sedimentation rate measurement.

INTRODUCTION: With recent advances in technology, many manual tests are being replaced by automated devices due to a wide range of advantages. One of these tests is the erythrocyte sedimentation rate (ESR) test that is used to determine inflammatory activity. This study aimed to evaluate the agreement between the Starrsed Interliner sedimentation device and the gold standard method, that is the Westergren method, used in ESR measurement. METHODS: One hundred fifty-one patients who presented to Gaziantep University Faculty of Medicine, Sahinbey Training and Research Hospital were included in this study. ESR values were measured simultaneously within 2 hours using the ESR analyzer Starrsed Interliner device and the gold standard method of measuring ESR, that is the Westergren method, from blood samples collected from the same patients in EDTA and citrate tubes. RESULTS: Agreement between the results from the Starrsed Interliner device and the Westergren method was evaluated using the Intraclass Correlation method. Consequently, a poor correlation was observed at values <20 mm/h, a moderate correlation was observed at values 20 to 80 mm/h and >80 mm/h, and an excellent correlation was observed when all results were considered. Method comparison was conducted according to the Passing-Bablok regression analysis (y = -1.50 + 0.75x) (P < .0001). The mean difference between the two methods was 10.1 according to the Bland-Altman analysis. CONCLUSIONS: Despite the advantages of the Starrsed Interliner device, such as lower laboratory workloads, lower costs and turnaround time, the difference between the two methods, as found in this study, may lead to different clinical interpretations for results in some patient.

Metformin reduces ovarian ischemia reperfusion injury in rats by improving oxidative/nitrosative stress.

OBJECTIVE: To assess the preventive role of metformin on rat ovarian ischemia reperfusion injury. MATERIALS AND METHODS: Forty rats were divided equally into five groups; Group 1: sham, Group 2: surgical control with 3-hr torsion and detorsion, Group 3: 50 mg/kg p.o. metformin 30 min before 3-hr torsion, Group 4; metformin just after detorsion, Group 5; metformin 30 min before torsion and just after detorsion. Bilateral ovaries and blood sample were obtained seven days after detorsion for biochemical and histopathological evaluation. RESULTS: Ovarian tissue total anti-oxidant status (TAS) levels were significantly increased in group 4 when compared to group 1, 2 and 3 (all p < 0.01). In addition, there was a significant decrease in tissue oxidative stress index (OSI) level in group 4 with respect to group 2 (p < 0.01). Moreover, serum levels of OSI were significantly higher in group 2 with respect to group 1 and 5 (both p < 0.05). Similarly, there was significant increase in serum levels of peroxynitrite in group 2 as compared to serum levels in group 3 and 5 (p < 0.01 and 0.05, respectively). Furthermore, there were significant decrease in histopathological scores metformin and sham groups when compared to rats in the control group (Group 2). CONCLUSION: Metformin reduces ischemia reperfusion injury in rat torsion detorsion model by improving histopathological and biochemical findings including TAS, OSI and peroxynitrite.

Melatonin attenuates ovarian ischemia reperfusion injury in rats by decreasing oxidative stress index and peroxynitrite

Background/aim: To evaluate the protective effect of melatonin on ovarian ischemia reperfusion injury in a rat model. Materials and methods: Forty-eight rats were separated equally into 6 groups. Group 1: sham; Group 2: surgical control with 3-h bilateral ovarian torsion and detorsion; Group 3: intraperitoneal 5% ethanol (1 mL) just after detorsion (as melatonin was dissolved in ethanol); Group 4: 10 mg/kg intraperitoneal melatonin 30 min before 3-h torsion; Group 5:10 mg/kg intraperitoneal melatonin just after detorsion; Group 6:10 mg/kg intraperitoneal melatonin 30 min before torsion and just after detorsion. Both ovaries and blood samples were obtained 7 days after detorsion for histopathological and biochemical analysis. Results: In Group 1, serum levels of total oxidant status (TOS) (µmol H2O2 equivalent/g wet tissue)were significantly lower than in Group2 (P = 0.0023), while tissue TOS levels were lower than in Group 3 (P = 0.0030). Similarly, serum and tissue levels of peroxynitrite in Group 6were significantly lower than those ofGroup 2 (P = 0.0023 and P = 0.040, respectively). Moreover, serum oxidative stress index (OSI) (arbitrary unit) levels were significantly increased in Group 2 when compared to groups 1 and 6 (P = 0.0023 and P= 0.0016, respectively) and in Group 3 with respect to groups 1, 4, 5, and 6 (P = 0.0023, P = 0.0026, P = 0.0008, and P = 0.0011, respectively). Furthermore, there was a significant decrease in histopathological scores including follicular degeneration, vascular congestion, hemorrhage, and inflammation in the melatonin and sham groups in comparison with control groups. Additionally, primordial follicle count was significantly higher in Group 6 than in Group 2 (P = 0.0002). Conclusion: Melatonin attenuates ischemia reperfusion damage in a rat torsion/detorsion model by improving histopathological and biochemical findings including OSI and peroxynitrite.