Alleviating sepsis: Revealing the protective role of costunolide in a cecal ligation and puncture rat model.

Objectives: Sepsis poses a significant threat to human life, rendering it a burdensome medical disease. Despite significant advancements, the current state of medical science still lacks a viable and efficacious cure. Costunolide (COST) is a multifaceted sesquiterpene lactone that exhibits a range of actions, including anti-inflammatory and antioxidant properties. We investigated the potential impacts of COST on a rat sepsis model caused by cecal ligation and puncture (CLP). Materials and Methods: We created an experimental rat model with the following groups: SHAM, CLP, CLP+low dose COST, and CLP+high dose COST. Blood, kidney, and lung samples were collected. Inflammatory mediators such as interleukin-1beta (IL-1ß), IL-6, tumor necrosis factor-alpha (TNF- α), and nuclear factor kappa-B (NF-κB) were investigated. In addition, we assessed oxidative stress by measuring 8-Hydroxydeoxyguanosine (8-OHdG) immunopositivity, MDA levels, glutathione (GSH), and superoxide dismutase (SOD) activity. Histopathological and immunohistochemical examinations backed up our findings. Results: Compared to the CLP group, the COST group showed a reduction in inflammatory and oxidative stress indicators. The expression of inflammatory mediators was suppressed by COST, and histological examinations revealed improvements in kidney and lung tissues in the treatment groups. Conclusion: Our study highlights the preventive effects of COST against CLP-induced sepsis-related injury. Considering its beneficial effects against many diseases, COST is worthy as to be evaluated against sepsis.

Costunolide prevents renal ischemia-reperfusion injury in rats by reducing autophagy, apoptosis, inflammation, and DNA damage.

Objectives: Renal ischemia-reperfusion (I/R) is a vital health condition leading to acute kidney injury. Costunolide (COST) is an actively used molecule clinically for its anti-inflammatory, antioxidant, and immunomodulatory properties. In the present study, we searched for the possible protective effects of COST against renal ischemia/reperfusion (I/R) injury in rats. Materials and Methods: We established a renal I/R rat model. We divided forty rats into four groups: group I (sham), group II (I/R), group III (I/R+COST 5 mg/kg), and group IV (I/R+COST 10 mg/kg). We collected blood, kidney, and lung samples for analysis. Results: COST administration performed anti-oxidant and anti-inflammatory activity by reducing oxidant parameters and proinflammatory cytokine levels. COST alleviated DNA damage through declining 8-hydroxydeoxyguanosine (8-OHdG) levels. In addition, COST diminished tubular damage and inflammation by reducing kidney injury molecule-1 (KIM-1) production. COST administration also ameliorated apoptosis and autophagy by decreasing caspase-3 and microtubule-associated protein light chain 3B (MAPLC3, LC3B) expression. Conclusion: COST demonstrated protective effects against renal I/R-induced injury.

The effects of tarantula cubensis extract on renal ischemia reperfusion injury in rats.

BACKGROUND: Renal ischemia-reperfusion (IR) related acute kidney injury (AKI) is an important health problem and has not yet been fully treated. Tarantula cubensis extract (TCE) is a homeopathic drug that has antiinflammatory and antioxidant effects. This study aimed to investigate the effects of TCE on renal ischemia-reperfusion injury in rats. METHODS: This study was carried out on 48 Spraque-Dawley male rats, which were divided into six groups. The first, second, and third groups were control, sham, and IR groups, respectively. Group four received IR and 0.2 mL of 96% ethanol. Group five and six received ischemia and reperfusion and TCE 0.01 and 0.1 mg per rat (which correspond to approximately 0.04 mg/kg, and 0.4 mg/kg), respectively. Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), total antioxidant status (TAS), and total oxidant status (TOS) levels in renal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress index (OSI) was obtained by proportioning TAS and TOS. Superoxide dismutase (SOD), myeloperoxidase (MPO) activities, and malondialdehyde (MDA) levels were determined by manual spectrophotometric methods. The histopathological changes were evaluated via hematoxylineosin and immunohistochemical staining. RESULTS: In IR group, renal tissue TNF-α and IL-1ß levels were significantly higher than control group (p < 0.0001 for both), and low(p < 0.0001 for both) and high dose (p < 0.0001 for both) TCE administration decreased these markers. Low and high doses of TCE decreased OSI values compared with IR group (p = 0.04 and p = 0.001 respectively). Although TCE decreased MDA levels, it was not statistically significant. MPO levels significantly decreased. In addition, TCE has been found to prevent hemorrhage, cast formation, and dilatation caused by IR in renal tissues stained with hematoxylin-eosin. And also, the most intense nuclear factor kappa B (NFκB) and caspase-3 immunopositivity found in IR group was decreased in both of the TCE groups. DISCUSSION: Although TCE showed a protective effect by inhibiting inflammation against IR damage in renal tissues, there was no clear effect on oxidative stress. Larger and more detailed studies are needed to clarify the issue.

Therapeutic effects of apocynin on ovarian ischemia-reperfusion induced lung injury.

Ovarian ischemia-reperfusion (I-R) injury may damage remote organs, including the lungs. We investigated whether apocynin, a NADPH oxidase inhibitor, might protect against ovarian I-R induced apoptosis in the lungs of rats. Bilateral ovarian I-R was induced for 3 h, then apocynin was applied at two concentrations. Lung tissue was evaluated using spectrophotometric and immunohistochemical methods. We found that I-R increased total oxidant status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) levels, and immunostaining of nuclear factor kappa-B (NF-κB), light chain 3B (LC3B), interleukin 1-beta (IL-1ß), caspase-3 and tumor necrosis factor-alpha (TNF-α), but decreased superoxide dismutase (SOD) values. Apocynin application to I-R injured rats enhanced recovery of lung tissue oxidants and improved both histology and frequency of apoptosis.

An Overview of Ischemia-Reperfusion Injury: Review on Oxidative Stress and Inflammatory Response.

Ischemia-reperfusion is a common health problem leading to several health conditions. The pathophysiology of ischemia-reperfusion is quite complex. Oxidative stress and inflammatory response contribute to ischemia-reperfusion mechanisms. Various parameters like proinflammatory cytokines, reactive oxygen species, occur during ischemia-reperfusion . There are several ways to investigate these values through biochemical and histopathologic findings. Malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, interleukin 6, interleukin 1ß, tumor necrosis factor alpha, caspase-3, nuclear factor-kappa ß, and LC3B (microtubu le-associated protein light chain 3, LC3) can be evaluated among these indicators.

Urapidil alleviates ovarian torsion detorsion injury via regulating oxidative stress, apoptosis, autophagia, and inflammation.

OBJECTIVES: This study aimed to determine anti-inflammatory, antioxidant, and antiapoptotic properties of urapidil (Ura) against ovarian torsion detorsion (T/D) injury in rats. MATERIALS AND METHODS: 40 female Wistar albino rats were grouped as sham, T/D, T/D+dimethyl sulfoxide (DMSO), T/D+Urapidil (Ura) 0.5 mg/kg (low dose), and T/D+Urapidil (Ura) 5 mg/kg (high dose) groups. In treatment groups, Ura was administered intraperitoneally just before detorsion. Biochemical parameters (TAS, TOS, MDA, MPO, and SOD) and immunohistochemical (IL-1ß, TNF-α, NF-κB, LC3B, and Caspase-3) analyzes were performed. RESULTS: In the T/D group, OSI and MPO levels were elevated significantly while TAS values decreased compared with the sham group. A significant difference occurred in the low dose treatment group in TAS and OSI levels compared with the T/D group. In the high dose treatment group, significant elevation in TAS but reduction in OSI and MDA levels were observed compared with the T/D group. Immunohistochemical staining resulted in IL-1ß, TNF-α, NF-κB, LC3B, and caspase-3 immunopositivity in the T/D group, while Ura treatment decreased those parameters. Intensive congestion and hemorrhage were observed in the T/D group, but contrary to this, treatment groups had alleviated congestion and hemorrhage. CONCLUSION: These results suggest that Ura demonstrated protective effects against ovarian T/D injury via anti-oxidative, anti-inflammatory, and anti-apoptotic features.

Protective effects of gallic acid on doxorubicin-induced cardiotoxicity; an experimantal study.

The present study aims to examine the possible beneficial effects of gallic acid (GA) against doxorubicin-induced cardiotoxicity in the experimental model. Rats were weighed and divided into groups. Groups as following; control, gallic acid (GA), doxorubicin (DOX) and GA + DOX groups. At the end of the experiment, rats were sacrificed and heart tissue removed. The tissues were analysed in terms of biochemical (MDA, SOD, CAT, GSH, GPx), pathological (hyaline degeneration, Zenkerin necrosis, hyperaemia) and immunohistochemical (TNF-α, Cox-2). MDA level decreased and antioxidant enzyme activities increased in GA + DOX group compared to doxorubicin group. TNF-α, Cox-2 expression levels were severe in the DOX group. Also, pathologic tissue damage in heart tissue increased due to doxorubicin. Additionally, pathologic tissue damage and TNF-α, Cox-2 expression levels decreased in GA + DOX group. According to our findings, GA has protective effect against doxorubicin-induced cardiotoxicity.

Agomelatine prevents indomethacin-induced gastric ulcer in rats.

BACKGROUND: Gastric ulcer is a very common gastrointestinal disease that may be dangerous and even may lead to death. The current study was conducted to detect the prophylactic effects of agomelatine on indomethacin-induced gastric ulcer. METHODS: In this study, a total of 5 groups were created as the sham, ulcer, omeprazole, agomelatine 1 mg/kg and agomelatine 5 mg/kg groups. The effects of agomelatine on indomethacin-induced gastric injury were investigated. Total antioxidant and oxidant levels; the oxidant parameters like oxidative stress index and the inflammation markers such as tumor necrosis factor-α, interleukin-1ß, interleukin-6 and interleukin-10 levels in stomach tissue were determined by ELISA. In addition, the gastric mucosal injury occurred in stomach wall was examined with histopathological methods. RESULTS: While the levels of the inflammatory markers, total oxidant status and oxidative stress index increased at an obvious level especially in the indomethacin group, the total antioxidant status levels decreased. It was observed that these parameters were improved at a significant level in agomelatine 1 mg/kg and agomelatine 5 mg/kg groups when compared to ulcer group; and the results were similar to omeprazole group. It was also observed that our histopathological findings were consistent with all our other results. CONCLUSIONS: The results of this study showed that agomelatine usage in indomethacin-induced gastric ulcer model provides beneficial results.

Preventive effects of fraxin on ischemia/reperfusion-induced acute kidney injury in rats.

AIM: Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute kidney failure. The oxidative stress and inflammatory process are the underlying mechanisms of IR injury. It has been purposed in this study to research the possible protective effects of fraxin on kidney injury induced by IR. MATERIAL AND METHODS: 32 Sprague Dawley male rats were divided into 4 groups. The groups were organized as follows; sham, IR, IR + fraxin 10 mg/kg, and IR + 50 mg/kg fraxin groups. Some oxidant, antioxidant and inflammatory parameters were evaluated in kidney tissues removed at the end of our experimental study. KEY FINDINGS: It was detected that the oxidant and proinflammatory markers increased and antioxidant parameters decreased in IR group but the results significantly reversed in treatment groups compared to IR group. And also, 8-OHdG, NF-κB, HAVCR1 immunopositivities were at severe levels and these results attenuated in IR fraxin + 10 mg/kg, and IR + fraxin 50 mg/kg groups. SIGNIFICANCE: These presented results have shown that fraxin performed protective effects against kidney injury induced by IR.

Evodiamine alleviates kidney ischemia reperfusion injury in rats: A biochemical and histopathological study.

Renal ischemia/reperfusion (I/R) injury resulting in acute renal failure, is a major clinical problem due to its high mortality rate. Renal I/R increases the reactive oxygen species, secretion of inflammatory cytokines, chemokines and other factors. This suggests that initiating the apoptosis process in the presence of oxidative stress may play a role in life-threatening conditions, such as ischemia. Ischemia reperfusion-induced renal damage can result in renal failure and death. Although many treatment procedures have been carried out to reduce or destroy renal I/R damage in experimental models, so far, a routine method of treatment has not yet been found. For this reason, the current study was planned to investigate the possible protective effects of evodiamine on tissue damage caused by ischemia-reperfusion in kidney tissue in rats and an experimental renal I/R model was used for this purpose. Four groups were formed in the study: the control, sham control, ischemia reperfusion (I/R), and evodiamine (10 mg/kg) + I/R groups. The effects of evodiamine against kidney I/R injury were investigated. TAS (total oxidant status), TOS (total oxidant status), interleukin-1ß (IL-1ß), IL-6, IL-10 and tumor necrosis factor-α levels were determined by enzyme-linked immunosorbent assay. The oxidative stress index was calculated from TAS and TOS levels. In addition, the renal ischemia reperfusion injury was examined histopathologically. The IL-10 and TAS levels in the I/R group decreased when compared with the control and Sham groups, while these levels increased in the evodiamine group. Histopathologic examination revealed that caspase 3 and nuclear factor-κB levels decreased in the evodiamine group compared with the I/R group. The application of evodiamine significantly reduced ischemia reperfusion-induced kidney damage due to its antioxidant, anti-inflammatory and antiapoptotic properties.

Anti-oxidant and anti-inflamatuar effectiveness of caftaric acid on gastric ulcer induced by indomethacin in rats.

In this study, we evaluated the anti-oxidant and anti-inflammatory effect of caftaric acid against ulcer produced by indomethacin in gastric mucosa. Female Sprague Dawley albino rats were divided into five groups: control (saline group, n = 8), negative control (indomethacin group, n = 8), positive control (omeprazole group, n = 8), low dose therapy (caftaric acid, n = 8), and high dose therapy (caftaric acid, n = 8). At the end of the experiment, all rats were sacrificed and gastric mucosa samples were removed for macroscopic and biochemical analysis. In our study, we detected that oxidant parameter values and cytokine levels increased in the negative control group, but total antioxidant status reduced, whereas, cytokine and oxidant parameter levels were significantly reduced due to low and high doses of caftaric acid administration. But another important point to note is that high dose caftaric acid therapy performed gastroprotective effect as omeprazole. In the macroscopic evaluation, there were reductions in ulcer sizes with a low and high dose of caftaric acid administration in contrast to the negative control group. As a result of our study, caftaric acid showed anti-oxidant and anti-inflammatory effects in indomethacin-induced gastric ulcer in rats.

8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion injury.

The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na+ and Ca 2+ . The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1ß, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia-reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.

Protective effect of salusin-α and salusin-ß against ethanol-induced gastric ulcer in rats.

BACKGROUND: Alcohol consumption has been found to be associated with gastric ulcers, including gastric mucosal lesions. Salusin-α and salusin-ß are bioactive peptides having 28 and 20 amino acids, respectively. Salusin-α and salusin-ß immunoreactivity has been detected in the stomach and in the intestines. It has been reported that the salusins regulate the cytokine levels and decrease the infarct area in the heart tissue after ischemia. In this study, we investigated the effects of the salusins in the gastric injury formed with ethanol. METHODS: Thirty-two sprague Dawley male rats were randomly divided into four groups, including eight rats in each group as follows: Group 1: control; Group 2: ethanol 5 mL/kg; Group 3: ethanol 5 mL/kg+5 nmol/kg salusin-α; Group 4: ethanol 5 mL/kg+5 nmol/kg salusin-ß. RESULTS: The salusin-α level increased at a significant level in the ulcer group formed with ethanol (p<0.001); the change in the salusin-ß level is not significant. As for malondialdehyde (p<0.05) and myeloperoxidase (p<0.001), when compared with the control group, tumor necrosis factor-α (p<0.05) levels increased in the group to which ethanol was applied and decreased significantly with the application of salusins. Levels of GSH and IL-1ß did not change at a significant level. In addition, histopathologic analysis demonstrated that, in salusin-administered groups, mucosal injury and caspase-3 expressions were reduced. CONCLUSIONS: The suppression of salusin-α and salusin-ß on caspase-3 expression by means of their effects on oxidative injury and TNF-α levels shows that these two hormones could serve as anti-ulcerative agents.

Effect of intermittent hypoxia on the cardiac HIF-1/VEGF pathway in experimental type 1 diabetes mellitus.

OBJECTIVE: High altitude and hypoxic preconditioning have cardioprotective effects by increasing coronary vascularity, reducing post-ischemic injury, and improving cardiac function. Our purpose was to examine if intermittent hypoxia treatment has any restoring effects related to the possible role of the HIF-1/VEGF pathway on diabetic cardiomyopathy. METHODS: Wistar Albino male rats (n=34) were divided into four groups: control (C), intermittent hypoxia (IH), diabetes mellitus (DM), and diabetes mellitus plus intermittent hypoxia (DM+IH). Following a streptozotocin (STZ) injection (50 mg/kg, i.p.), blood glucose levels of 250 mg/dL and above were considered as DM. IH and DM+IH groups were exposed to hypoxia 6 h/day for 42 days at a pressure corresponding to 3000 m altitude. Twenty-four hours after the IH protocol, hearts were excised. Hematoxylin and eosin-stained apical parts of the left ventricles were evaluated. Hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor 164 (VEGF164), and VEGF188 polymerase chain reaction products were run in agarose gel electrophoresis. Band density analysis of UV camera images was performed using Image J. The data were compared by one-way ANOVA, repeated measures two-way ANOVA, and the Kruskal-Wallis test. RESULTS: The percent weight change was lower in the DM group than in the controls (p=0.004). The tissue injury was the highest in the DM group and the least in the IH group. Diabetes decreased, whereas the IH treatment increased the vascularity. A decrease was observed in the VEGF188 mRNA levels in the DM+IH group compared with the C group, but there were no difference in HIF-1α and VEGF164 mRNA levels between the groups. CONCLUSION: The IH treatment restored the diabetic effects on the heart by reducing tissue injury and increasing the capillarity without transcriptional changes in HIF-1/VEGF correspondingly.