Molsidomine decreases hyperoxia-induced lung injury in neonatal rats.

BACKGROUND: The study's objective is to evaluate if Molsidomine (MOL), an anti-oxidant, anti-inflammatory, and anti-apoptotic drug, is effective in treating hyperoxic lung injury (HLI). METHODS: The study consisted of four groups of neonatal rats characterized as the Control, Control+MOL, HLI, HLI + MOL groups. Near the end of the study, the lung tissue of the rats were evaluated with respect to apoptosis, histopathological damage, anti-oxidant and oxidant capacity as well as degree of inflammation. RESULTS: Compared to the HLI group, malondialdehyde and total oxidant status levels in lung tissue were notably reduced in the HLI + MOL group. Furthermore, mean superoxide dismutase, glutathione peroxidase, and glutathione activities/levels in lung tissue were significantly higher in the HLI + MOL group as compared to the HLI group. Tumor necrosis factor-α and interleukin-1ß elevations associated with hyperoxia were significantly reduced following MOL treatment. Median histopathological damage and mean alveolar macrophage numbers were found to be higher in the HLI and HLI + MOL groups when compared to the Control and Control+MOL groups. Both values were increased in the HLI group when compared to the HLI + MOL group. CONCLUSIONS: Our research is the first to demonstrate that bronchopulmonary dysplasia may be prevented through the protective characteristics of MOL, an anti-inflammatory, anti-oxidant, and anti-apoptotic drug. IMPACT: Molsidomine prophylaxis significantly decreased the level of oxidative stress markers. Molsidomine administration restored the activities of antioxidant enzymes. Molsidomine prophylaxis significantly reduced the levels of inflammatory cytokines. Molsidomine may provide a new and promising therapy for BPD in the future. Molsidomine prophylaxis decreased lung damage and macrophage infiltration in the tissue.

Effects of noopept on ocular, pancreatic and renal histopathology in streptozotocin induced prepubertal diabetic rats.

Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine and metabolic changes during the pubertal period complicate management of DM. Noopept is a cognitive enhancer that exhibits antidiabetic properties. We investigated the effect of noopept on the histopathology of the cornea, retina, kidney and pancreas in pubertal diabetic rats. We allocated 60 prepubertal male rats randomly into six groups of 10: untreated control (C), DM control (DC), noopept control (NC), DM + noopept (D + N), DM + insulin (D + I) and DM + insulin + noopept (D + I + N). DM was induced by streptozotocin in the DC, D + N, D + I and D + I + N groups. Noopept was administered to the NC, D + N and D + I + N groups; insulin was administered to the D + I and D + I + N groups for 14 days. On day 18 of the experiment, animals were sacrificed and eyes, kidneys and pancreata were excised for histological investigation. Renal tubule diameter and corneal and retinal thickness were increased significantly in DC groups compared to the control group. The D + I, D + N and D + I + N groups exhibited fewer DM induced pathological changes than the DC group. The D + I + N group exhibited no significant differences in renal tubule diameter and corneal and retinal thickness compared to the DC group. Our findings suggest that noopept is protective against DM end organ complications in streptozotocin induced diabetic pubertal rats.

Protective Role of Diospyros lotus L. in Cisplatin-Induced Cardiotoxicity: Cardiac Damage and Oxidative Stress in Rats

Objectives: Cisplatin is a powerful chemotherapeutic drug that is used to treatment a wide variety of cancers. Despite clinical data demonstrating the cardiotoxic effect of cisplatin, few studies have been carried to improve the cardiotoxicity of cisplatin. In cisplatin-induced toxicity, oxidative stress plays a critical role. This study determined the effect of Diospyros lotus L. fruit (DL), a powerful antioxidant plant, on heart damage caused by cisplatin through histological examination and oxidative stress parameters. Materials and Methods: Twenty eight male rats were randomly divided into four groups. An isotonic solution was given to the control group. A single dose of 7 mg/kg cisplatin was administered intraperitoneally to the cisplatin group. 1.000 mg/kg DL was given by gavage for 10 days to the DL group. Cisplatin and DL were administered together in the same doses to the treatment group. Thiobarbituric acid reactive substances (TBARS) levels, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and total glutathione (GSH) level were measured in the heart tissue of the experimental rats. Histological examination was also performed to determine any damage to the hearts of the experimental rats. Results: While TBARS levels in the cisplatin group increased significantly, SOD, CAT, GPx activities, and total GSH level decreased significantly. TBARS levels decreased significantly and SOD, CAT, GPx activities and GSH levels increased with DL treatment. According to the histological examination, histopathological differences were observed in the cisplatin group. Histopathological findings were either absent or decreased in the DL-treated group. Conclusion: Results of the study showed that DL therapy reduced oxidative stress and histological changes caused by cisplatin. DL could be a potential candidate for reducing cardiac damage caused by cisplatin.

An investigation of histopathological changes and bioaccumulation in tissues of rainbow trout (Oncorhynchus mykiss) after exposure to dodine.

The purpose of this research is to determine ecotoxicological effects of dodine (n-dodecylguanidini acetate) on aquatic environments. Though dodine is widely used as a fungicide in agriculture, but there is no much data about its ecotoxicology. In this regard, we investigated bioaccumulation levels and histological alterations on the tissues of muscle, liver and gills in Rainbow Trout (Oncorhynchus mykiss) against different doses (0.01, 0.1, 0.5 and 1 mg/L) of Dodine exposure. The tissues of fish were extracted according to QUECHERS method and analyzed by mass spectrometer (LC-MS-MS). Neither of the applied dodine doses resulted in killing 50% of the total individuals in the experimental groups. However, 48 hours after doses, behaviors such as instability, anomaly in swimming or sudden jumping movements were observed. Histological results of the study showed deteriorations of the radiological pattern of hepatocytes, sinusoidal dilatations, hemorrhages, edemas, mononuclear cell infiltrations, vascular congestions, hyperplasia and hypertrophy in liver, gill and muscle tissues. Accumulation of dodine in tissues correlated with increase of dose. The maximum level of active substance accumulation in tissues were measured 96 hours after application of 1 mg/L dodine dose -in order- in gills, muscles and liver. The accumulations were statistically significant (p < 0.05) when compared with control group.

The protective effects of apocynin in hyperoxic lung injury in neonatal rats.

AIM: Inflammation and oxidate stress are significant factors in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to investigate the efficacy of apocynin (APO), an anti-inflammatory, antioxidant, and antiapoptotic drug, in the prophylaxis of neonatal hyperoxic lung injury. METHOD: This experimental study included 40 neonatal rats divided into the control, APO, BPD, and BPD + APO groups. The control and APO groups were kept in a normal room environment, while the BPD and BPD + APO groups were kept in a hyperoxic environment. The rats in the APO and BPD + APO groups were administered intraperitoneal APO, while the control and BPD rats were administered ordinary saline. At the end of the trial, lung tissue was evaluated with respect to the degree of histopathological injury, apoptosis, oxidant and antioxidant capacity, and severity of inflammation. RESULT: The BPD and BPD + APO groups exhibited higher mean histopathological injury and alveolar macrophage scores compared to the control and APO groups. Both scores were lower in the BPD + APO group in comparison to the BPD group. The BPD + APO group had a significantly lower average of TUNEL positive cells than the BPD group. The lung tissue examination indicated significantly higher levels of mean malondialdehyde (MDA), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the BPD group compared to the control and APO groups. While the TNF-α and IL-1ß levels of the BPD + APO group were similar to that of the control group, the MDA and TOS levels were higher compared to the controls and lower compared to the BPD group. The BPD group demonstrated significantly lower levels/activities of mean total antioxidant status, glutathione reductase, superoxide dismutase, glutathione peroxidase in comparison to the control and APO groups. While the mean antioxidant enzyme activity of the BPD + APO group was lower than the control group, it was significantly higher compared to the BPD group. CONCLUSION: This is the first study in the literature to reveal through an experimental neonatal hyperoxic lung injury that APO, an anti-inflammatory, antioxidant, and antiapoptotic drug, exhibits protective properties against the development of BPD.

Does Chrysin prevent severe lung damage in Hyperoxia-Induced lung injury Model?

BACKGROUND: Oxidative stress and inflammation play a critical role in the etiopathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study was to evaluate the preventive effect of Chrysin (CH), an antioxidant, antiinflammatory, antiapoptotic and antifibrotic drug, on hyperoxia-induced lung injury in a neonatal rat model. METHODS: Forty infant rats were divided into four groups labeled the Control, CH, BPD, and BPD + CH. The control and CH groups were kept in a normal room environment, while the BPD and BPD + CH groups were kept in a hyperoxic (90-95%) environment. At the end of the study, lung tissue was evaluated with respect to apoptosis, histopathological damage and alveolar macrophage score as well as oxidant capacity, antioxidant capacity, and inflammation. RESULTS: Compared to the BPD + CH and control groups, the lung tissues of the BPD group displayed substantially higher levels of MDA, TOS, TNF-α, and IL-1ß (p < 0.05). While the BPD + CH group showed similar levels of TNF-α and IL-1ß as the control group, MDA and TOS levels were higher than the control group, and significantly lower than the BPD group (p < 0.05). The BPD group exhibited considerably lower levels of TAS, SOD, GSH, and GSH-Px in comparison to the control group (p < 0.05). The BPD and BPD + CH groups exhibited higher mean scores of histopathological damage and alveolar macrophage when compared to the control and CH groups (p ≤ 0.0001). Both scores were found to be lower in the BPD + CH group in comparison to the BPD group (p ≤ 0.0001). The BPD + CH group demonstrated a significantly lower average of TUNEL and caspase-3 positive cells than the BPD group. CONCLUSION: We found that prophylaxis with CH results in lower histopathological damage score and reduces apoptotic cell count, inflammation and oxidative stress while increasing anti-oxidant capacity.

Effects of noopept on cognitive functions and pubertal process in rats with diabetes.

AIM: Type 1 diabetes (T1DM) is a common chronic disease in childhood. Increasing insulin resistance in puberty gives rise to higher doses of insulin usage in treatment. Of this reason new approaches in treatment are needed. Noopept researches suggest it to have anti-diabetic properties. We tried to determine the effects of noopept on pubertal diabetes. MAIN METHOD: The research was made with 60 prepubertal, 28 day-old, male, Sprague Dawley rats. The rats were divided into randomised 6 groups (n = 10/group). i) Control, ii) Diabetes Control, iii) Noopept Control, iv) Diabetes + Noopept, v) Diabetes + Insulin, vi) Diabetes + Insulin + Noopept. T1DM model was induced by streptozotocin on postnatal 28th day. 0.5 mg/kg noopept and 1 IU insulin were administered intraperitoneally for 14 days. Blood glucose and body weight measurements, puberty follow-up and MWM tests were performed. Hippocampus, hypothalamus and testis were evaluated histologically. Hypothalamic GnRH and kisspeptin were studied immunohistochemically. Serum LH, FSH and insulin, hippocampal homogenate NGF and BDNF levels were determined by ELISA. KEY FINDINGS: Delayed puberty was normalized by noopept (p < 0.05). Blood glucose levels were lower in noopept-administered diabetic groups (p < 0.05). Noopept decreased HOMA-IR in insulin administered diabetic group (p < 0.05). Number of degenerated cells in hippocampus and testis were higher in diabetes control group when compared with other groups (p < 0.05). GnRH immunoreactivity in Diabetes + Noopept group was increased when compared to insulin + noopept group (p = 0.018). There was no difference in kisspeptin, serum LH, FSH, hippocampal NGF-BDNF levels and spatial learning assessment among groups (p > 0.05). SIGNIFICANCE: Noopept may have positive effect in treatment of pubertal diabetes.

Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury.

The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia-reperfusion injury (IRI). It was determined that transient receptor potential melastatin-2 (TRPM2) channels and phospholipase A2 (PLA 2 ) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of N-( p-amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA 2 enzyme inhibitor on renal IRI. A total of 36 male Sprague-Dawley rats were divided into four groups: control, ischemia-reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase-3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM-1, NGAL, interleukin-18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase-3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI.

The effect of hypericum perforatum on kidney ischemia/reperfusion damage.

It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague-Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR + HP Group which was treated with 50 mg/kg of HP. The right kidneys of the rats were removed, and the left kidney developed ischemia during the 45th min, and reperfusion occurred in the following 3rd h. The histopathological findings and also the level of Malondialdehyde (MDA), Glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) enzyme activations in the renal tissues were measured. Blood Urea Nitrogen (BUN), Creatinin (Cre) from serum samples were determined. The levels of BUN, Cre, and kidney tissue MDA increased at a significant level, and the SOD, CAT, and GSH-PX enzyme activity decreased at a significant level in the I/R group, compared with the Control Group (p < 0.05). In the I/R + HP group, the levels of MDA decreased at a significant level compared to the I/R group, while the SOD, CAT, and GSH-PX activity increased (p < 0.05). In histopathological examinations, it was observed that the tubular dilatation and epithelial desquamation regressed in the IR + HP Group when compared with the I/R Group. It has been shown with the histological and biochemical results in this study that HP is protective against acute renal I/R.