Can adalimumab prevent from acute effects of lipopolysaccharide induced renal injury in rats?

PURPOSE: Lipopolysaccharides is well-known in the acute renal injury process. It causes widespread activation of inflammatory cascades. Tumor necrosis factor (TNF)-α and interleukin (Il)-6 are essential proinflammatory cytokines that can induce the production of other cytokines in host response. Adalimumab suppresses TNF-α, IL-1ß, and IL-6. We aimed to evaluate whether adalimumab would prevent the toxicity of lipopolysaccharide on the rat renal tissue. METHODS: Adult female Wistar rats were divided into four groups. To the control group, only intraperitoneal saline injection procedure was carried out. For adalimumab group, adalimumab was injected at a dose for two days. For lipopolysaccharide group, animals were injected with lipopolysaccharide (a dose). For lipopolysaccharide-adalimumab group, animals were given adalimumab treatment before the injection of lipopolysaccharide. Histopathological changes and immunohistochemical analysis for TNF-α and IL-6 were determined. RESULTS: The pathological changes and immunohistochemical staining for TNF-α or IL-6 were similar for control and adalimumab groups (p > 0.05). The lipopolysaccharide group had significantly higher distorted features in the renal tissues (p < 0.001), and also significantly prominent immunohistochemical staining for TNF-α or IL-6 (0.003), compared to the control group. No severe pathological feature was detected in the lipopolysaccharide-adalimumab group, but moderate necrosis was found in all cases (p = 0.003). TNF-α staining and IL-6 staining in the lipopolysaccharide group was found to significantly prominent compared to lipopolysaccharide-adalimumab group (p = 0.013). CONCLUSIONS: Because of its anti-inflammatory property, adalimumab pretreatment may have protective effects on experimental kidney injury. Adalimumab could be considered as a protective agent to acute effects of lipopolysaccharide induced renal injury.

Direct oral anticoagulant agents attenuate temporary aortic occlusion-induced renal oxidative and inflammatory responses in rats.

Background: This study aims to investigate the effects of different direct oral anticoagulants on experimental renal injury induced by temporary infrarenal aortic occlusion. Methods: A total of 35 male Wistar rats (250 to 350 g) were randomly allocated to any of the five groups: sham, ischemia-reperfusion, rivaroxaban, dabigatran, and apixaban groups. Sham group underwent median laparotomy. Ischemia-reperfusion group was given saline gavage for one week. Animals in the other groups received rivaroxaban (3 mg/kg), dabigatran (15 mg/kg), or apixaban (10 mg/kg) daily once for one week via oral gavage. The infrarenal abdominal aorta was clamped for 60 min, and reperfusion was maintained for 120 min in the ischemia-reperfusion, rivaroxaban, dabigatran, and apixaban groups. At the end of reperfusion, kidneys were harvested for biochemical and histopathological analysis. Results: Renal total antioxidant capacity was reduced, and total oxidant status, interleukin-1 beta, and tumor necrosis factor-alpha were elevated in the ischemia-reperfusion group, compared to the sham group (p<0.005). Histological damage scores were also higher in the ischemia-reperfusion group (p<0.005). Administration of direct oral anticoagulants caused an increase of total antioxidant capacity and reduction of total oxidant status, tumor necrosis factor-alpha, and interleukin-1 beta in the rivaroxaban, dabigatran, and apixaban groups compared to the ischemia-reperfusion group (p<0.005). Histological damage scores were lower in the rivaroxaban and dabigatran groups than the ischemia-reperfusion group scores (p<0.005). Conclusion: Direct oral anticoagulants reduce aortic clamping-induced renal tissue oxidation and inflammation. Rivaroxaban and dabigatran attenuate ischemia-reperfusion-related histological damage in kidneys.

Borate reduces experimental supra-celiac aortic clamping-induced oxidative stress in lung and kidney, but fails to prevent organ damage.

BACKGROUND: This study aims to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB) on aortic clamping-induced lung and kidney tissue oxidation, tissue inflammation, and histological damage in a rat model. METHODS: A total of 28 adult female Wistar albino rats were randomly allocated to four equal groups: Control group, ischemia-reperfusion group, dimethyl sulfoxide group, and 2-APB group. Animals in the control group underwent median laparotomy. In the remaining groups, supra-celiac aorta was clamped for 45 min and, then, reperfusion was constituted for 60 min. The 2-APB (2 mg/kg) was administered before clamping. The remaining groups received saline (ischemia-reperfusion group) or dimethyl sulfoxide (dimethyl sulfoxide group). Kidney and lung tissue samples were harvested at the end of reperfusion. RESULTS: Aortic occlusion caused increased tissue total oxidant status and reduced total antioxidant status and glutathione levels in the ischemia-reperfusion and dimethyl sulfoxide groups. Tissue interleukin-1 beta and tumor necrosis factor-alpha levels, nuclear factor kappa beta activation, and histological damage severity scores were also higher in these groups. The 2-APB treatment eliminated the increase in total oxidant status and the decrease in total antioxidant status and glutathione levels. It also caused a decrease in the interleukin-1 beta levels, although it did not significantly alter the tumor necrosis factor-alpha levels, nuclear factor kappa beta immunoreactivity, and histological damage scores. CONCLUSION: Borate exerted a beneficial antioxidant effect as evidenced by reduced oxidative stress; however, it did not inhibit nuclear factor kappa beta activation and prevent histological damage in supra-celiac aortic clamping-induced kidney and lung injury in rats.

Probiotic Saccharomyces boulardii Alleviates Lung Injury by Reduction of Oxidative Stress and Cytokine Response Induced by Supraceliac Aortic Ischemia-Reperfusion Injury in Rats

Abstract Objectives: Ischemia-reperfusion injury is an important cause of multiple organ failure in cardiovascular surgery. Our aim is to investigate the effect of the probiotic Saccharomyces boulardii on oxidative stress, inflammatory response, and lung injury in an experimental model of aortic clamping. Methods: Twenty-one Wistar rats were randomized into three groups (n=7). Control group animals received saline gavage for a week before undergoing median laparotomy. In other groups, supraceliac aorta was clamped for 45 minutes to induce ischemia followed by reperfusion for 60 minutes. In the ischemia-reperfusion group, saline gavage was given preoperatively for one week. Ischemia-reperfusion+probiotic group rats received probiotic gavage for seven days before aortic clamping. The levels of oxidative stress markers and pro-inflammatory cytokines were determined in both serum and lung tissue samples. Ileum and lung tissues were harvested for histological examination. Results: Ischemia-reperfusion caused severe oxidative damage and inflammation evident by significant increases in malondialdehyde and cytokine levels (tumor necrosis factor alpha and interleukin-1 beta) and decreased glutathione levels in both serum and lung tissues. There was severe histological tissue damage to the lung and ileum in the ischemia-reperfusion group. Probiotic pretreatment before aortic clamping caused significant suppression of increases in serum and lung tissue malondialdehyde and tumor necrosis factor alpha levels. Histological damage scores in tissue samples decreased in the ischemia-reperfusion+probiotic group (P<0,005). Conclusions: Oral supplementation of probiotic S. boulardii before supraceliac aortic ischemia-reperfusion in rats alleviates lung injury by reducing oxidative stress, intestinal cellular damage, and modulation of inflammatory processes.

Probiotic Saccharomyces boulardii Alleviates Lung Injury by Reduction of Oxidative Stress and Cytokine Response Induced by Supraceliac Aortic Ischemia-Reperfusion Injury in Rats.

OBJECTIVES: Ischemia-reperfusion injury is an important cause of multiple organ failure in cardiovascular surgery. Our aim is to investigate the effect of the probiotic Saccharomyces boulardii on oxidative stress, inflammatory response, and lung injury in an experimental model of aortic clamping. METHODS: Twenty-one Wistar rats were randomized into three groups (n=7). Control group animals received saline gavage for a week before undergoing median laparotomy. In other groups, supraceliac aorta was clamped for 45 minutes to induce ischemia followed by reperfusion for 60 minutes. In the ischemiareperfusion group, saline gavage was given preoperatively for one week. Ischemia-reperfusion+probiotic group rats received probiotic gavage for seven days before aortic clamping. The levels of oxidative stress markers and pro-inflammatory cytokines were determined in both serum and lung tissue samples. Ileum and lung tissues were harvested for histological examination. RESULTS: Ischemia-reperfusion caused severe oxidative damage and inflammation evident by significant increases in malondialdehyde and cytokine levels (tumor necrosis factor alpha and interleukin-1 beta) and decreased glutathione levels in both serum and lung tissues. There was severe histological tissue damage to the lung and ileum in the ischemia-reperfusion group. Probiotic pretreatment before aortic clamping caused significant suppression of increases in serum and lung tissue malondialdehyde and tumor necrosis factor alpha levels. Histological damage scores in tissue samples decreased in the ischemia-reperfusion+probiotic group (P<0,005). CONCLUSIONS: Oral supplementation of probiotic S. boulardii before supraceliac aortic ischemia-reperfusion in rats alleviates lung injury by reducing oxidative stress, intestinal cellular damage, and modulation of inflammatory processes.

TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats.

PURPOSE: To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury. METHODS: Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination. RESULTS: Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). CONCLUSIONS: Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.

TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats

Abstract Purpose To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury. Methods Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination. Results Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). Conclusions Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.

A new predictor of atrial fibrillation after coronary artery bypass graft surgery: HATCH score.

The aim of this study was to investigate the association between HATCH score and atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. 369 patients (103 patients with AF and 266 patients without AF) undergoing isolated CABG surgery were analyzed. Complete medical records were retrospectively collected to investigate HATCH score. The median age of patients with AF was significantly higher than the median age of non-AF group (60.8±10.0 years vs 67.8±9.5 years, P<0.001). HATCH score was significantly higher in patients who developed AF after CABG surgery than the non-AF group (P=0.017). Multivariate logistic regression analysis showed that HATCH score (OR 1.334; 95% CI 1.022 to 1.741, P=0.034) was an independent predictor of AF after CABG surgery. Receiver operating characteristic curve analysis showed that the cut-off point of HATCH score related to predict AF was >1 (two or more), with a sensitivity of 42% and specificity of 70%. Patients with elevated preoperative HATCH score may have higher risk for AF after CABG surgery.

The effects of ozone on bacterial growth and thiol-disulphide homeostasis in vascular graft infection caused by MRSA in rats.

PURPOSE:: To investigate the microbiological, inflammatory and oxidant effects of adjuvant ozone administration in experimental rat vascular graft infection model which has not been previously investigated. METHODS:: Forty adult Wistar rats were divided into Sham, Control, Vancomycin, Ozone, Vancomycin+Ozone groups. Grafts were inoculated with Methicillin-resistant Staphylococcus aureus (MRSA) strain and implanted subcutaneously. Rats were treated intraperitoneally with ozone and /or intramuscularly with vancomycin for 10 days. Grafts were evaluated by quantitative bacterial cultures. Blood samples were harvested for determination of thiol-disulphide and cytokine profiles. RESULTS:: There was no significant difference in bacterial counts between Control and Ozone Groups. In the Ozone Group median colony count was significantly higher than the Vancomycin and Vancomycin+Ozone Groups. Total thiol and disulphide levels increased and disulphide/native thiol and disulphide/total thiol ratios decreased in Ozone Group significantly. Albumin levels decreased significantly in Vancomycin and Vancomycin+Ozone Groups compared to the Sham Group. IL-1 and TNF-alpha levels significantly increased in infected rats. Decreased levels of VEGF due to infection reversed by ozone therapy in control and vancomycin groups. CONCLUSIONS:: We didn't observe any benefit of the agent on MRSA elimination in our model. Likewise, effects of ozone on thiol-disulphide homeostasis and inflammatory cytokines were contradictory.

The effects of ozone on bacterial growth and thiol-disulphide homeostasis in vascular graft infection caused by MRSA in rats

Abstract: Purpose: To investigate the microbiological, inflammatory and oxidant effects of adjuvant ozone administration in experimental rat vascular graft infection model which has not been previously investigated. Methods: Forty adult Wistar rats were divided into Sham, Control, Vancomycin, Ozone, Vancomycin+Ozone groups. Grafts were inoculated with Methicillin-resistant Staphylococcus aureus (MRSA) strain and implanted subcutaneously. Rats were treated intraperitoneally with ozone and /or intramuscularly with vancomycin for 10 days. Grafts were evaluated by quantitative bacterial cultures. Blood samples were harvested for determination of thiol-disulphide and cytokine profiles. Results: There was no significant difference in bacterial counts between Control and Ozone Groups. In the Ozone Group median colony count was significantly higher than the Vancomycin and Vancomycin+Ozone Groups. Total thiol and disulphide levels increased and disulphide/native thiol and disulphide/total thiol ratios decreased in Ozone Group significantly. Albumin levels decreased significantly in Vancomycin and Vancomycin+Ozone Groups compared to the Sham Group. IL-1 and TNF-alpha levels significantly increased in infected rats. Decreased levels of VEGF due to infection reversed by ozone therapy in control and vancomycin groups. Conclusions: We didn't observe any benefit of the agent on MRSA elimination in our model. Likewise, effects of ozone on thiol-disulphide homeostasis and inflammatory cytokines were contradictory.

Association of Preoperative Platelet-to-Lymphocyte Ratio with Atrial Fibrillation after Coronary Artery Bypass Graft Surgery.

OBJECTIVE: The aim of this study was to investigate the association between platelet-to-lymphocyte ratio (PLR) and atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. SUBJECTS AND METHODS: A total of 125 patients were retrospectively analyzed. AF was diagnosed using standard clinical criteria, and PLR was calculated as the ratio of the platelets to lymphocytes, obtained from the blood samples that were taken in the fasting state before CABG surgery. The association of different variables with postoperative AF and PLR was calculated using univariate and multivariate analysis. The receiver operating characteristics curve was used to determine the sensitivity and specificity of PLR and the optimal cutoff value for predicting post-CABG AF. RESULTS: Of the 125 patients, 50 with AF (mean age: 67.0 ± 9.5 years, 38 males and 12 females) and 75 patients without AF (mean age: 61.1 ± 9.1 years, 58 males and 17 females) were identified, and the difference in the mean age was statistically significant (p = 0.01). PLR was also significantly higher in those with AF (152.8 ± 82.2) than those without AF (118.2 ± 32.9) (p = 0.012). Univariate analysis showed that age and PLR were associated with AF after CABG surgery (p < 0.001 and p = 0.005, respectively). Using a multivariate logistic regression model with the backward elimination method, age and PLR remained as independent predictors of AF after CABG surgery (p < 0.001 and p = 0.005, respectively). PLR levels >119.3 predicted postoperative AF with 64% sensitivity and 56% specificity (AUC: 0.634, p = 0.012). CONCLUSION: In this study, age and PLR level were independent predictors of AF after CABG surgery. Patients with an elevated preoperative PLR were at higher risk of AF after CABG surgery.

Ozone preconditioning attenuates contrast-induced nephropathy in rats.

BACKGROUND: Contrast-induced nephropathy (CIN) is an important complication of vascular interventions. Ozone therapy can induce tolerance to ischemic insults, a phenomenon known as ozone oxidative preconditioning (OOP). The aim of this study was to investigate the effects of OOP on CIN. MATERIALS AND METHODS: Thirty-two Wistar rats were randomized into four groups (n = 8). The control group had intravenous saline injection. The contrast media (CM) group had intravenous meglumine/sodium diatrizoate injection to form CIN. The ozone (O3) group received intraperitoneal ozone for 5 d before the induction of CIN. The oxygen (O2) group was given an equal amount of oxygen for 5 d before the induction of CIN. The animals were sacrificed 48 h after the administration of contrast agent or saline. Kidneys were harvested, and blood samples were obtained. Renal function tests, serum and renal tissue malondialdehyde (MDA), and nitric oxide (NO) levels and renal oxidant system parameters were determined. Histologic examination was performed for renal injury. RESULTS: Serum blood urea nitrogen (BUN), creatinine, and serum and renal MDA were increased after contrast exposure. Renal NO was decreased, and there was prominent tubular necrosis in the CM group. Serum BUN, creatinine, serum and renal MDA, and grade of tubular necrosis were decreased in the O3 group as compared with those in the CM group. The levels of serum and renal NO and renal total antioxidant system in O3 group were higher than the levels in the CM group. CONCLUSIONS: OOP attenuates experimental CIN. This effect is suggested to be mediated by reinforcement of renal antioxidant defenses and maintenance of renal NO levels.