Vücut enzimatik ve enzimatik olmayan karmaşık bir antioksidan savunma sistemine sahiptir. Antioksidan mekanizmalar vücut dokuları için zararlı etkilere sahip olan serbest radikallere karşı savunma sistemi geliştirirler. Süperoksit dismutaz (SOD), katalaz (CAT) ve glutatyon peroksidaz (GPX) hücrede serbest radikallere karşı temel savunma hattını oluştururlar. Serbest radikaller özellikle mitokondriyal enerji üretim yoluyla sürekli olarak üretilir. Serbest radikallerin hücrede birikmesi oksidatif strese ve hücresel hasara neden olur. Hücre reaktif oksijen türlerinde artışın nörodejeneratif, kardiyovasküler, diyebet ve böbrek hastalıkları gibi bir çok hastalıkların patogenezinde rol oynadığı ifade edilmektedir. SOD, CAT ve GPx’in hücresel hasarı önlemedeki rolü sürekli olarak araştırılmaktadır. Bu derleme makalesi, SOD, CAT ve GPX antioksidan enzimlerinin oksidatif stresi önlemedeki rolünü açıklamak için yazılmıştır.

The aim of this study was to investigate the oxidative damage and inflammatory effects in the hippocampus and cerebellum in lipopolysaccharide (LPS)-induced sepsis model and possible ameliorating effects of pregabalin (PG). Twenty four female Wistar Albino rats (12 month old) were divided into 3 groups as follows: Group I (Control; 0.1 ml/gavage and i.p. saline, single dose), Group II (LPS; 5 mg/kg LPS, i.p, single dose), Group III (LPS + PG; 5 mg/kg LPS, i.p, single dose + 30 mg/kg, gavage, single dose). DNA damage, ischemia-modified albumin (IMA), total oxidant status (TOS), total antioxidant status (TAS) oxidative stress index (OSI), leukocyte (WBC), lymphocyte, neutrophil, hemoglobin (HGB), erythrocyte (RBC), and thrombocyte counts were measured in blood and brain tissues. Histopathological and immunohistochemical evaluation of Caspase- 3, G-CSF, IL-6, SAA, iNOS expressions were conducted using hippocampus and cerebellum tissues. Comet analysis score, lymphocytes, neutrophils, WBC, IMA, TOS and OSI values were increased in Group II compared with to Group I (p < 0.05). IMA levels in blood, TOS and OSI levels in the brain were significantly decreased in Group III compared to Group II (p < 0.05). We observed increased hemorrhages, neutrophils, leukocytes infiltrations and neuron degeneration in Group II compared to Group I. Caspase 3, G-CSF, IL-6, SAA, iNOS expressions were increased in group II compared to Group I (p < 0.001). Pregabalin partly ameliorated the damage caused by the exposure to LPS in hippocampus and cerebellum; however, further studies are needed to determine pregabalin's possible protective effects at different doses and with different techniques.

This study sought to assess the protective effects of resveratrol and avocado oil in relation to paracetamol-induced hepatotoxicity in rats. The rats were divided into five groups, namely the control, paracetamol (600 mg/kg), resveratrol (RES; 10 mg/kg) + paracetamol, avocado oil (AVO; 200 mg/kg) + paracetamol, and RES + AVO + paracetamol groups. The hepatoprotective activity was evaluated by measuring biochemical parameters such as the total antioxidant status (TAS) and the total oxidant status (TOS) in each rat’s liver homogenates. Any DNA damage was assessed by means of a comet assay. The results showed that the TOS levels were significantly increased in the paracetamol group when compared with the control group. The TOS levels were found to be significantly lower in the paracetamol groups, in comparison with the RES, AVO, and RES + AVO groups. Moreover, the TAS levels significantly increased in the RES and RES + AVO groups when compared with the paracetamol group. The histopathological examination revealed necrotic areas in the rats’ livers. Pretreatment with both RES and RES + AVO was found to reverse the oxidative stress parameters, DNA damage, and necrosis induced by paracetamol. These results suggest that a combination of REV and AVO may protect against paracetamol-induced hepatotoxicity due to their antioxidant properties.

We investigated the ameliorating effects of astaxanthin (AXA) on methotrexate (MTX) induced damage to the cerebral cortex, hippocampus, cerebellar cortex and blood. We used 24 female Wistar albino rats divided into three groups of eight as follows: sham/control group, single dose of saline intraperitoneally (i.p.) and 7 days orally; MTX group, single dose of 20 mg/kg MTX (i.p.); MTX + AXA group, single dose of 20 mg/kg MTX i.p.+ 100 mg/kg AXA orally for 7 days. For all groups we measured total oxidant status (TOS) and total antioxidant status (TAS) in the cerebral cortex, hippocampus and blood. Histological sections of cerebral cortex, hippocampus and cerebellar cortex were inspected microscopically. Caspase-3 (cas-3), granulocyte colony-stimulating factor (GCSF), growth related oncogene (GRO), inducible nitric oxide synthase (iNOS) and myelin basic protein (MBP) were estimated immunohistochemically in the cerebral cortex, hippocampus and cerebellar cortex. In the MTX group, TAS was decreased significantly in the cerebral cortex, hippocampus and blood, while TOS was significantly increased. AXA significantly ameliorated oxidative stress parameters in the cerebral cortex and hippocampus. Histopathological examination revealed degeneration, edema and hyperemia in the cerebral cortex, hippocampus and cerebellar cortex in the MTX group. AXA treatment ameliorated histopathological changes. MTX decreased MBP expression in cerebral cortex. Although MBP expression was decreased in the cerebral cortex, hippocampus and cerebellar cortex stimulated with MTX, the expressions of cas-3, GCSF, GRO and iNOS were significantly increased. AXA ameliorated the expression of cas-3, GCSF, GRO, iNOS and MBP. AXA exhibits anti-inflammatory, antioxidant and anti-apoptotic effects on MTX induced toxicity in the cerebral cortex, hippocampus and cerebellar cortex by increasing MBP expression, regulating inflammatory cytokine release and reducing oxidative stress.

Objective(s): Methotrexate (MTX) is a widely used chemotherapeutic agent that, however, is known to have serious side effects such as neurotoxicity. In the present study, we aimed to evaluate the possible favorable effects of ramelteon (RMLT) on MTX-induced cerebral toxicity.Materials and Methods: Thirty-two male Wistar albino rats were divided into four groups: Control group, MTX group (20 mg/kg MTX, IP, single dose), MTX+RMLT group (20 mg/kg MTX, IP, single dose + 10 mg/kg RMLT, by gavage, 7 days), and RMLT group (10 mg/kg RMLT, by gavage, 7 days).Results: In the MTX group, increased levels of total oxidant status (TOS) and oxidative stress index (OSI) levels and decreased levels of total antioxidant status (TAS) level were observed. RMLT significantly reversed oxidative stress parameters. Real-time PCR analysis revealed that MTX increased the expressions of Beclin-1 and autophagy-related gene 12 (ATG12). These expressions were significantly decreased by RMLT. Vacuolar changes, apoptotic cells, and inflammatory cell infiltration induced by MTX were ameliorated by RMLT treatment. Increased tumor necrosis factor-alpha (TNF-alpha) and Caspase-3 activities induced by MTX were returned to their normal levels by RMLT.Conclusion: All our results demonstrate that RMLT alleviates the harmful effects of MTX on the cerebral cortex tissue. Therefore, RMLT may be considered for supportive therapy for preventing side effects of MTX in patients needing MTX therapy.