Tissue Malondialdehyde Levels Research Articles

Does the addition of metformin to carboplatin treatment decreases ovarian reserve damage associated with carboplatin usage?

BackgroundWe aimed to determine whether adding metformin to carboplatin treatment would reduce the damage to ovarian reserve associated with carboplatin use.MethodsWe included 35 adult female non-pregnant albino Wistar rats approximately three months old, weighing 220–310 g. The rats were divided into five groups of seven rats according to the treatment they received. Carboplatin and salin was given to Group 2, and carboplatin plus metformin was given to Group 3. Group 4 was administered only metformin. Group 5 was administered only salin. Carboplatin was given to Groups 2 and 3 as a single dose on the 15th day, while metformin was given to Groups 3 and 4 during the 28-day experiment. After oophorectomy, histopathologic analyses of primordial, primary, secondary, and tertiary Graff follicles according to the epithelial cells surrounding the oocyte and total follicular number were conducted per section. Serum Anti-Mullerian Hormone (AMH), tissue catalase, and malonyl dialdehyde levels were measured and compared within each group.ResultsThe baseline and 15th-day serum AMH values of the menstrual cycle were compared among the groups, and no statistically significant differences were observed (p > 0.05). Group 3, which was given both carboplatin and metformin, had statistically significantly higher 28th-day AMH levels than Group 2, which was given only carboplatin and saline (p < 0.001). The number of primordial follicles in Group 3 was found to be statistically significantly higher than in Group 2 (p < 0.001). Tissue catalase enzyme levels in Group 3 were statistically significantly higher than in Group 2 (p < 0.001). Tissue malondialdehyde levels in Group 2 were statistically significantly higher than tissue malondialdehyde levels in Groups 3 and 4 (p < 0.001).ConclusionsMetformin may attenuate carboplatin-induced ovarian damage, possibly through its antioxidative effects.

N-Acetylcysteine Improves Renal Function and Reduces Tissue Malondialdehyde Levels in Glycerol-Induced Acute Kidney Injury

Introduction: The etiology of myoglobinuric acute kidney injury involves oxidative injury brought on by the Fenton reaction and myoglobin redox cycle. Renal tubules may be harmed, and lipid peroxidation compounds with vasoconstrictor characteristics may be produced. N-acetylcysteine (NAC) is an antioxidant shown to improve renal microcirculation and have protective effects in various models of renal damage. The aim of the study was to demonstrate the protective impact of NAC in glycerol-induced rats by measuring tissue malondialdehyde (MDA) level and renal function test (RFT), and to determine the correlation between the protective effect and NAC dose.Methods: This study measured tissue malondialdehyde (MDA) and renal function to examine any protective effect of NAC in a glycerol-induced rat model and to determine whether the effect was dose-related. Five groups of male Wistar rats were used: 1) saline control group, (2) glycerol (50%, 8mL/kg, i.m) plus saline i.v group, 3) glycerol plus NAC (100 mg/kg)-treated group, 4) glycerol plus NAC (200 mg/kg)-treated group, 5) glycerol plus NAC (400 mg/kg)-treated group. At 24 hrs, after glycerol injection, rats were sacrificed, cardiac blood was taken for renal function measurement, and renal tissues were removed for thiobarbituric acid MDA level assessment.Results: Our study revealed that glycerol administration significantly amplified renal tissue MDA, serum creatinine, and BUN (blood urea nitrogen) levels. However, NAC administration dampened the MDA increment and renal function deterioration (p&lt;0.05). Moreover, tissue MDA, BUN, and serum creatinine levels were significantly correlated to NAC dose (r=0.485; r=0.491; rs=0.544, respectively; all p&lt;0.05), indicating that NAC protection declines by dose increments.Conclusion: In this glycerol-induced acute kidney injury rat model, the administration of intravenous NAC 100 mg/kg reduced lipid peroxidation and improved renal function. Nevertheless, the protective effect was diminished in higher doses.

Effect of levothyroxine administration on oxidative stress and cytokine levels in rats with experimental hypothyroidism

In this study, it was aimed to determine the effects of levothyroxine (L-T4) administration on serum free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and serum total antioxidant capacity (TAC), serum total oxidant capacity (TOC), oxidative stress index (OSI) and superoxide dismutase (SOD) activity, liver malondialdehyde (MDA) and the effects of cytokines on tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in rats with experimental hypothyroidism. In the study, 48, 39-day-old, male Wistar albino rats were randomly divided into 3 groups containing 16 rats in each as control, hypothyroid and levothyroxine (L-T4) treated hypothyroid group. The rats in the control group were injected with 1 mL of saline and the rats in the hypothyroid group were injected via intraperitoneal (i.p.) route with 6-n-propyl thiouracil (PTU) at a dose of 10 mg/kg/day for 28 days. In the levothyroxine treated group, after induction of hypothyroidism 5 µg of levothyroxine diluted in 1 mL of sodium chloride (NaCl) administered via i.p. route for 15 days. At the end of the study, serum and liver samples were taken from the rats. In hypothyroidism group, serum fT3, fT4 and TAK levels as well as SOD (P&lt;0.001) activity decreased statistically compared to the control group while serum TSH, TOC, OSI (P&lt;0.001), liver MDA (P&lt;0.01), TNF-α and IL-6 (P&lt;0.001) levels increased significantly. The decreased serum fT3, fT4, TAC levels and SOD (P&lt;0.001) activity in the hypothyroidism group increased with levothyroxine administration whereas the increased serum TSH, TOC, OSI and tissue MDA (P&lt;0.01), TNF-α and IL-6 (P&lt;0.001) levels were found to be decreased and approached to control levels. In conclusion, it has been shown that levothyroxine administration is effective against PTU-induced hypothyroidism in rats, inhibits lipid peroxidation and increases antioxidant status, minimizes the levels of inflammatory markers and protects against PTU-induced liver damage in rats. Because, the potential therapeutic use of levothyroxine in the treatment of hypothyroidism is thought to be appropriate.

Network Pharmacology-based Investigation and Experimental Discovery of Resveratrol’s Mechanism of Liver Ischemia Reperfusion-Induced Oxidative Stress Damage

Background: This study was aimed to investigate the hepatoprotective effect of RSV against oxidative stress damage which we induced an experimental liver Ischemia-reperfusion (I/R) model in rats. Methods: Female albino rats were divided into three groups (n = 8). Contrast to the control group, 1 ml saline (0.09 % NaCl) was administered intraperitoneally two days before the operation and after reperfusion in the sham group. 1 ml of 50 mg/kg Resveratrol was administered to the treatment group until two days before the operation. In addition, a single dose of 1 ml of Resveratrol was re-administered after reperfusion. The duration of liver ischemia/reperfusion was determined as 30 minutes in all groups. At the end of this experiment, antioxidant enzyme (CAT, SOD) activities and the levels of malondialdehyde (MDA) were measured as spectrophotometric in liver tissues homogenates. Result: Our study, tissue injuries were observed in the ischemia/reperfusion and Sham groups (p less than 0.001). In this study, significant decreases were observed in tissue MDA levels in the treatment group compared to the sham and control groups (p less than 0.001). In addition, antioxidant enzyme levels (SOD. CAT) were significantly increased in the treatment group compared to the control and Sham groups. Liver tissue samples were examined for hepatocyte damage and histopathological grade of the groups were shown. In our study, tissue injuries were observed in the ischemia/reperfusion and Sham groups (p less than 0.001). Liver edema, necrosis and PMNL infiltration were found to be decreased in the treatment group compared to the control group. The association of resveratrol with oxidative damage was also determined by network pharmacology analysis.

Acetaminophen impairs ferroptosis in the hippocampus of septic mice by regulating glutathione peroxidase 4 and ferroptosis suppressor protein 1 pathways.

Neuronal ferroptosis is a major cause of cognitive impairment and mortality in patients with sepsis-associated encephalopathy (SAE). A low dose of acetaminophen (APAP) in septic mice can prevent ferroptosis in the hippocampal tissue; however, the underlying mechanism is unknown. This study aimed to investigate the mechanism by which APAP reduces ferroptosis in the hippocampal tissues of septic mice. A mouse model of SAE was established, and the ferroptosis pathway inhibitors RSL3 and iFSP1+RSL3 were used in addition to APAP for the interventions, respectively. The 7-day survival rate of the mice was recorded, and cognitive function was examined using the Morris water maze test. Hematoxylin and eosin staining was performed to observe hippocampal tissue damage. Hippocampal iron and malondialdehyde (MDA) were measured using chemical colorimetric methods. Immunofluorescence was used to detect the reactive oxygen species (ROS) content in hippocampal tissues. RSL3 reversed the efficacy of APAP on improving cognitive dysfunction in septic mice but did not obviously reverse the survival rate of mice enhanced by APAP. RSL3 aggravated APAP-induced hippocampal tissue damage in mice attenuated by APAP. RSL3 inhibited glutathione peroxidase 4 (GPX4) expression and increased ferroptosis suppressor protein 1 (FSP1) and 4-hydroxy-2-nonenal (4-HNE) expression. RSL3 also reversed the effects of APAP in reducing iron, MDA, and ROS levels in the hippocampal tissues of septic mice. iFSP1+RSL3 further reversed the effect of APAP on ameliorating cognitive dysfunction in septic mice and successfully reversed the survival rate of mice enhanced by APAP. iFSP1+RSL3 aggravated APAP-induced cerebral hippocampal damage. iFSP1+RSL3 inhibited both GPX4 and FSP1, further reversing the effect of APAP on the reduction in iron, 4-HNE, ROS, and MDA levels in the cerebral hippocampus of mice with sepsis. These data suggest that APAP inhibits ferroptosis in the cerebral hippocampus of septic mice through the GPX4 and FSP1 pathways.

Protective effects of CAPE against testicular damage in streptozotocin-induced diabetic rats

Objective: The aim of this study was to investigate the protective effect of CAPE on oxidative stress and apoptosis against streptozotocin (STZ)-induced damage in rat testis after diabetes. Materials and methods: The rats were randomly divided into 4 groups: Control animals, Control animals given CAPE, STZ-induced diabetic animals, and STZ-induced diabetic rats given CAPE. Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg). Testicular damage was examined by using hematoxylin and eosin staining and apoptosis was determined by Caspase-3. Potential disorders associated with seminiferous tubular sperm formation were evaluated using the Johnsen score and seminiferous tubule diameters were measured using the Leica Q Win Plus Image Analysis System. Results: Diabetic rats showed an increase in degenerated germ cells along with a decrease in seminiferous tubule diameter. Also, Caspase-3 positive cells were significantly increased in diabetic rats compared to control rats. On the other hand, CAPE significantly reduced the damage and germ cell apoptosis in diabetic rat testis. In testis tissues samples. CAPE treatment significantly decreased the elevated tissue malondialdehyde levels, while increasing the reduced superoxide dismutase enzyme activity. Conclusion: These results suggest that CAPE administered intraperitoneally for 20 days to diabetic rats is a potentially beneficial agent that can be used to reduce testicular damage.

Arı Sütünün Tüketici Egzersize Bağlı Oksidatif Stres Üzerindeki Rolü

In this study, the effects of Royal Jelly (RJ) on oxidative stress caused by exhaustive swimming exercise in rat tissues were evaluated. Methods: Twenty four male Wistar albino rats were indiscriminately distributed into four experimental groups: Sedentary control (SC); SC with administration of RJ (100 mg kg-1) (SC + RJ); exhaustive swimming exercise (E); Exhaustive swimming exercise with administration of RJ (100 mg kg-1) (E + RJ). 100 mg kg-1 of RJ were dissolved in drinking water. Rats in the SC+RJ and E+RJ groups supplemented with RJ (100 mg kg-1) orally once a day for two weeks. Rats in groups E and E+RJ subjected to acute exhaustive swimming exercise on the 14th day of the study, then some biochemical parameters related to oxidative stress of all groups were measured. Results: The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and creatinine (CRE) levels significantly raised in the exercised rats compared with the sedentary rats (P &lt; 0.05). The decreased superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase (CAT) activities of muscular and hepatic tissues significantly increased and the high malondialdehyde (MDA) levels of muscular, hepatic and kidney tissues significantly reduced in exercised rats treated with RJ (P &lt; 0.05). Conclucion: Collectively, in this study, protective effects of RJ on tissues against oxidative damage after exhaustive exercise were observed.

Protective effects of scutellarin in experimental colitis in rats

ABSTRACT Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology for which effective treatments are lacking. Scutellarin is a flavonoid with anti-apoptotic, antioxidant and anti-inflammatory effects. We investigated the possible protective effects of scutellarin on UC induced by acetic acid in rats. We used five groups of male rats: control, scutellarin, UC, UC + scutellarin, UC + sulfasalazine. Colonic mucosal inflammation was evaluated microscopically. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and DNA fragmentation levels were measured. Colon tissue sections were evaluated using immunohistochemistry for Bcl-2 and Bax, TUNEL staining and histopathology. Pretreatment with scutellarin significantly reduced histological damage. Scutellarin significantly reduced serum and tissue levels of MDA, NO, IL-6 and TNF-α, and increased enzymatic activity of SOD and TAS. Scutellarin suppressed apoptosis by down-regulation of Bax, reduction of DNA fragmentation and increased expression of Bcl-2. Apoptosis was increased, while antioxidant enzymes were significantly decreased; some histopathologic disorders also were seen in the UC group. Administration of scutellarin ameliorated the pathological and biochemical alterations caused by UC in rats. We found that scutellarin might be protective against UC by down-regulating pro-inflammatory cytokines and suppressing apoptosis and oxidative stress.

The Effects of Dexmedetomidine on Abdominal Aortic Occlusion-Induced Ovarian Injury via Oxidative Stress and Apoptosis

Ischemia/reperfusion (I/R) induced ovarian damage is caused by various diseases such as ovarian torsion, ovarian transplantation, cardiovascular surgery, sepsis, or intra-abdominal surgery. I/R-related oxidative damage can impair ovarian functions, from oocyte maturation to fertilization. This study investigated the effects of dexmedetomidine (DEX), which has been shown to exhibit antiapoptotic, anti-inflammatory, and antioxidant effects, on ovarian I/R injury. We designed four study groups: group 1 (n = 6): control group; group 2 (n = 6): only DEX group; group 3 (n = 6): I/R group; group 4 (n = 6): I/R + DEX group. Then, ovarian samples were taken and examined histologically and immunohistochemically, and tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured. In the I/R group MDA levels, caspase-3, NF-κB/p65, 8-OHdG positivity, and follicular degeneration, edema, and inflammation were increased compared to the control group (p = 0.000). In addition, GSH levels were significantly decreased in the I/R group compared to the control group (p = 0.000). On the other hand, in the I/R + DEX treatment group MDA levels, caspase-3, NF-κB/p65, 8-OHdG positivity, follicular degeneration, edema, and inflammation findings were decreased than in the I/R group (p = 0.000, p = 0.005, p = 0.005, p = 0.001, p = 0.005, respectively). However, GSH levels increased significantly in the I/R + DEX treatment group compared to the I/R group (p = 0.000). DEX protects against ovarian I/R injury through antioxidation and by suppressing inflammation and apoptosis.

Efficacy of Veronica incana for Treating Osteoarthritis Induced by Monosodium Iodoacetate in Rats.

The aim of this study is to investigate the efficacy and the underlying mechanism of Veronica incana in osteoarthritis (OA) induced by intraarticular injection of monosodium iodoacetate (MIA). The selected major four compounds (A-D) of V. incana were found from fractions 3 and 4. Its structure elucidation was determined by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) data analysis and nuclear magnetic resonance (NMR) data comparison with literature. MIA (50 μL with 80 mg/mL) for the animal experiment was injected into the right knee joint. The V. incana was administered orally every day to rats for 14 days from 7 days after MIA treatment. Finally, we confirmed the four compounds: (A) verproside; (B) catalposide; (C) 6-vanilloylcatapol; and (D) 6-isovanilloylcatapol. When we evaluated the effect of V. incana on the MIA injection-induced knee OA model, there were a noticeable initial decreased in hind paw weight-bearing distribution compared to the Normal group (P < .001), but V. incana supplementation resulted in a significant increase in the weight-bearing distribution to the treated knee (P < .001). Moreover, the V. incana treatment led to a decrease in the levels of liver function enzymes and tissue malondialdehyde (P < .05 and .01). The V. incana significantly suppressed the inflammatory factors through the nuclear factor-kappa B signaling pathway and downregulated the expression of matrix metalloproteinases, which are involved in the degradation of the extracellular matrix (P < .01 and .001). In addition, we confirmed the alleviation of cartilage degeneration through tissue stains. In conclusion, this study confirmed the major four compounds of V. incana and suggested that V. incana could serve as an anti-inflammatory candidate agent for patients with OA.

Hepatoprotective Effects of Biochanin A Against Acetaminophen-induced Liver Toxicity in Mice

Background: Acetaminophen (APAP), a common analgesic agent, is hepatotoxic in overdose. N-acetylcysteine (NAC), as an APAP antidote, shows anaphylactic reactions and has low efficacy in APAP poisoning in high doses. Objectives: This study was designed to examine the hepatoprotective effect of biochanin A (BA) in a mice model of acetaminophen-induced hepatotoxicity. Methods: To evaluate APAP-induced oxidative stress, the liver tissue level of malondialdehyde (MDA) and glutathione (GSH) and the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), catalase, and superoxide dismutase (SOD) were measured. Histological analysis was performed. Results: APAP-induced hepatotoxicity was manifested by inflammation, acinar hepatic necrosis, and fatty degeneration, as well as an increase in the levels of ALP, ALT, AST, MDA, and a decrease in the SOD, catalase (CAT), and GSH. Pre-treatment with BA at low doses (10 and 20 mg/kg) reduced ALT, AST, and MDA levels and raised the SOD, GSH, and CAT levels. Moreover, it normalized the structure of liver tissue. Conclusions: The results of this study indicated that BA protected the liver from APAP-induced injury. Protection may be due to the inhibition of oxidative stress, which reduces liver inflammation.

The Effect of Amnion Cell Culture Medium on Wound Healing: An Experimental Animal Study.

Fetal wound repair seems a relatively efficient process when compared to wound repair during adulthood, which may be explained by the effects of the fetal environment. This study examined the effects of an amnion cell culture medium (ACCM) on skin wound healing in a rat experimental model. Sixteen adult female Wistar albino rats were used in this experimental animal study (treatment group, n = 8; control group, n = 8). Surgical wounds were formed on the dorsal skin of each rat. A commercially available ACCM was administered daily over each of the wound in the treatment group for 14 days and the control group did not receive any treatment. Wounds were evaluated for tissue perfusion with laser doppler, tissue superoxide dismutase (SOD), glutathione peroxidase (GPX), and malondialdehyde (MDA) levels as well as histopathological examination. Controls had significantly higher tissue SOD levels when compared to the treatment group (10.0 ± 3.2 vs 6.7 ± 1.2, P = .005); however, the 2 groups did not differ in terms of tissue GPX and MDA levels. For open wounds, inflammation and neovascularization were more prominent in the ACCM group at day 14. However, at day 21 neovascularization and granulation were more prominent in controls. For closed wounds, neovascularization was more prominent in controls at days 14 and 21. The 2 groups did not differ in terms of tissue perfusion. Although marginal difference was found between controls and ACCM group for several parameters, findings of this study do not support beneficial effect of ACCM on wound healing.

Weekend warrior exercise model for protection from chronic mild stress‑induced depression and ongoing cognitive impairment.

We aim to investigate the role and biological mechanisms of the weekend warrior (WW) exercise model on depression‑induced rats in comparison to the continuous exercise (CE) model. Sedentary, WW, and CE rats were subjected to chronic mild stress (CMS) procedure. CMS and exercise protocols continued for six weeks. Anhedonia was evaluated by sucrose preference, depressive behavior by Porsolt, cognitive functions by object recognition and passive avoidance, and anxiety levels by open field and elevated plus maze. After behavioral assessments, brain tissue myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, superoxide dismutase and catalase activities and GSH content, tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), IL‑1β, cortisol and brain‑derived neurotrophic factor levels and histological damage was assessed. CMS‑induced depression‑like outcomes with increases in anhedonia and decreases in cognitive measures that are rescued with both exercise models. The increased immobilization time in the Porsolt test was decreased with only WW. Exercise also normalized the suppression of antioxidant capacity and MPO increase induced by CMS in both exercise models. MDA levels also declined with both exercise models. Anxiety‑like behavior, cortisol levels, and histological damage scores were exacerbated with depression and improved by both exercise models. TNF‑α levels were depleted with both exercise models, and IL‑6 only with WW. WW was as protective as CE in CMS‑induced depression‑like cognitive and behavioral changes via suppressing inflammatory processes and improving antioxidant capacity.

Smilax china L. Polysaccharide Alleviates Dextran Sulphate Sodium-Induced Colitis and Modulates the Gut Microbiota in Mice.

This work aimed to investigate the preventive effect of Smilax china L. polysaccharide (SCP) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Smilax china L. polysaccharide was isolated by hot water extraction, ethanol precipitation, deproteinization, and purification using DEAE-cellulose column chromatography to yield three polysaccharides: SCP_C, SCP_A, and SCP_N. Acute colitis was induced by administering 3% (w/v) DSS in drinking water for 7 days. Sulfasalazine, SCP_C, SCP_A, and SCP_N were administered by gavage for 9 days. SCP_C, SCP_A, and SCP_N could significantly improve symptoms, as evidenced by the declining disease activity index (DAI), decreased spleen weight, increased length of the colon, and improved colonic histology. Moreover, SCP_C, SCP_A, and SCP_N increased serum glutathione and decreased the levels of pro-inflammatory cytokines, malondialdehyde, nitric oxide, and myeloperoxidase in colon tissues. Additionally, SCP_C, SCP_A, and SCP_N modulated gut microbiota via ascending the growth of Lachnospiraceae, Muribaculaceae, Blautia, and Mucispirillum and descending the abundance of Akkermansiaceae, Deferribacteraceae, and Oscillibacter in mice with UC. The results suggested that Smilax china L. polysaccharide ameliorates oxidative stress, balances inflammatory cytokines, and modulates gut microbiota, providing an effective therapeutic strategy for UC in mice.

BORİK ASİT SIÇANLARDA SİKLOFOSFAMİDİN NEDEN OLDUĞU KARACİĞER HASARINI İYİLEŞTİRİR

Introduction: The aim of the current study was to look into any potential ameliorative benefits of boric acid on liver damage in rats caused by cyclophosphamide (CTX). &#x0D; Materials and Methods: Four groups; control, boric acid, CTX, and boric acid + CTX, were created. Female Wistar albino rats were given daily injections of CTX (75 mg/kg) to create the liver damage model. Cyclophosphamide (75 mg/kg) was administered intraperitoneally, and boron (1.3 g/rat/day) was administered by gavage every day for two weeks in the boric acid+CTX group. The histopathological changes were evaluated in ovarian tissue staining with hematoxylin and eosin, masson tricrom, and periodic acid Schiff. We assessed ovarian tissue enzyme activity as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). &#x0D; Results: Images in the boric acid+CTX group had lower histological evaluations than those in the CTX group under the light microscope. According to the findings, boric acid reduced the levels of malondialdehyde (MDA) in the liver tissues. Additionally, boric acid improved the actions of oxidative stress indicators to reduce oxidative stress brought on by CTX and upregulated antioxidant parameters.&#x0D; Conclusion: In conclusion, our study have demonstrated that CTX- induced liver injury can be alleviated by reducing the tissue MDA levels, increasing the liver’s SOD, GSH-Px, and CAT activities. In order to reduce the liver damage caused by CTX, boric acid may be administered as a dietary supplement or functional food.

Punicalin attenuates LPS-induced acute lung injury by inhibiting inflammatory cytokine production and MAPK/NF-κB signaling in mice

BackgroundAcute lung injury (ALI) remains a significant cause of morbidity and mortality in critically ill patients. Novel therapies interfering with the inflammatory response has been an area of focus for infectious disease treatment. Punicalin has shown strong anti-inflammatory and antioxidative properties; however, its effect in ALI has not been previously explored. PurposeTo investigate the effects of punicalin in lipopolysaccharide (LPS)-induced ALI and explore the underlying mechanisms. MethodsLPS (10 mg/kg) was administered intratracheally to create the ALI model in mice. Punicalin (10 mg/kg) was administered intraperitoneally shortly after LPS to investigate survival rate, lung tissue pathological injury, oxidative stress, levels of inflammatory cytokines in BALF and lung tissue, neutrophil extracellular trap (NET) formation and its effects on NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. In vitro studies were performed to evaluate the inflammatory cytokine release and NET formation in LPS-induced (1 μg/ml) and punicalin-treated mouse neutrophils derived from the bone marrow. ResultsIn vivo, punicalin reduced mortality, lung injury score, lung wet-to-dry (W/D) weight ratio, protein concentrations in BALF and malondialdehyde (MDA) levels in lung tissues, and increased superoxide dismutase (SOD) levels in lung tissues of LPS-induced ALI mice. Increased secretion of TNF-α, IL-1β, and IL-6 in the BALF and the lungs of ALI mice was reversed by punicalin, whereas IL-10 was upregulated. Neutrophil recruitment and NET formation were also decreased by punicalin. Inhibition of NF-κB and MAPK signaling pathways was observed in punicalin-treated ALI mice. In vitro co-incubation with punicalin (50 μg/ml) inhibited the production of inflammatory cytokines and NET formation in LPS-treated neutrophils derived from mouse bone marrow. ConclusionPunicalin reduces inflammatory cytokine production, prevents neutrophil recruitment and NET formation, and inhibits the activation of NF-κB and MAPK signaling pathways in LPS-induced ALI.

Dexmedetomidine alleviates vacuolization and necrosis in tubular epithelial cells induced by aortic cross-clamping.

Acute kidney injury (AKI) is one of the main causes of mortality in patients undergoing emergency surgery due to an abdominal aortic aneurysm. This study aimed to determine the potential nephroprotective characteristics of dexmedetomidine (DMD) for the establishment of a standard therapeutic method for AKI. Thirty Spraque Dawley rats were allocated to 4 groups: control, sham, ischemia-reperfusion, and ischemia/reperfusion (I/R)+dexmedatomidine. Necrotic tubules, degenerative Bowman's capsule and vascular congestion were observed in the I/R group. In addition, there was an increase in tissue malondialdehyde (MDA), interleukin (IL)-1 and IL-6 levels in tubular epithelial cells. In contrast, we observed decreased tubular necrosis, IL-1, IL-6 and MDA levels in the DMD treatment group. DMD has a nephroprotective effect against acute kidney injury resulting from I/R, which is related to aortic occlusion used in the treatment of ruptured abdominal aortic aneurysms.

Does lithium attenuate the liver damage due to oxidative stress and liver glycogen depletion in experimental common bile duct obstruction?

In extrahepatic cholestasis, the molecular mechanisms of liver damage due to bile acid accumulation remain elusive. In this study, the activation of glutamatergic receptors was hypothesized to be responsible for bile acid-induced oxidative stress and liver damage. Recent evidence showed that lithium, as an N-methyl-d-aspartate receptor (NMDAR) GluN2B subunit inhibitor, may act on the glutamate/NMDAR signaling axis. Guinea pigs were assigned to four groups, as sham laparotomy (SL), bile duct ligated (BDL), lithium-treated SL (SL + Li) and lithium-treated BDL (BDL + Li) groups. Cholestasis-induced liver injury was evaluated by aspartate aminotransferase (AST), alanine transaminase (ALT), interleukin-6 (IL-6), tissue malondialdehyde (MDA), copper‑zinc superoxide dismutase and reduced glutathione levels. The liability of glutamate/NMDAR signaling axis was clarified by glutamate levels in both plasma and liver samples, with the production of nitric oxide (NO), as well as with the serum calcium concentrations. Blood glucose, glucagon, insulin levels and glucose consumption rates, in addition to tissue glycogen were measured to evaluate the liver glucose-glycogen metabolism. A high liver damage index (AST/ALT) was calculated in BDL animals in comparison to SL group. In the BDL animals, lithium reduced plasma NO and glutamate in addition to tissue glutamate concentrations, while serum calcium increased. The antioxidant capacities and liver glycogen contents significantly increased, whereas blood glucose levels unchanged and tissue MDA levels decreased 3-fold in lithium-treated cholestatic animals. It was concluded that lithium largely protects the cholestatic hepatocyte from bile acid-mediated damage by blocking the NMDAR-GluN2B subunit.

The toxic effects of anabolic steroids “nandrolone decanoate” on cardiac and skeletal muscles with the potential ameliorative effects of silymarin and fenugreek seeds extract in adult male albino rats

BackgroundAnabolic steroids (AS) are commonly abused by body builders and athletes aiming to increase their strength and muscle mass but unfortunately, the long-term use of AS may lead to serious side effects. Nandrolone Decanoate is one of the Class II anabolic androgenic steroids which quickly spread globally and used clinically and illicitly. Our research was directed to assess the toxic effects of anabolic steroids on cardiac and skeletal muscles in male albino rats and to evaluate the potential ameliorative effects of fenugreek seeds extract and silymarin.MethodsOur research was done on 120 male albino rats that were allocated into 6 groups; group I: Served as a control group, group II: Received the anabolic steroid Nandrolone Decanoate, group III: Received silymarin orally, group IV: Received fenugreek seeds extract orally, group (V): Received the anabolic steroid Nandrolone Decanoate and silymarin and group (VI): Received the anabolic steroid Nandrolone Decanoate and fenugreek seeds extract. By the end of the study, rats were sacrificed, and blood samples were collected for biochemical analysis and autopsy samples for histopathological examination.ResultsThe anabolic steroids toxic effects on rats showed a significant decrease in serum High Density Lipoprotein (HDL) level and increase in cholesterol, triglycerides, and Low-Density Lipoprotein (LDL) levels. There was a significant elevation in cardiac troponin I level. As regards to histopathological examination of the cardiac and skeletal muscles, the study showed marked degenerative changes and necrosis. Both silymarin and fenugreek seeds extract provided a protective effect on the biochemical and histopathological changes. The antioxidant effects of silymarin and fenugreek seeds extract were evaluated on the heart, skeletal muscles and showed that, the tissue levels of Superoxide dismutase (SOD), Catalase and reduced glutathione (GSH) decreased in AS treated rats compared to the control group. On the other hand, the tissue Malondialdehyde (MDA) levels were elevated.ConclusionsAnabolic steroids have a toxic effect on the cardiac and skeletal muscles of albino rats with improvement by treatment with fenugreek seeds extract and silymarin.

Sodium hydrogen sulfide may not protect the kidney against ischemia/reperfusion damage in male and female rats.

Renal ischemia/reperfusion (IR) injury is a pathologic phenomenon that caused to increase risk of mortality. The main objective of this study was to investigate the effect of sodium hydrogen sulfide (NaHS) on renal IR injury in male and female rats. Fifty-eight male and female rats were randomized into 4 groups of control, sham, IR, and IR + NaHS. The IR was performed by 45 min of ischemia by vessel clamping followed by 24 h reperfusion. The NaHS (100 µmol/kg) treatment was applied 10 min prior to IR. Finally, after 24 h of reperfusion, the measurements were performed. The serum levels of blood urea nitrogen, creatinine, tissue level of malondialdehyde, and kidney tissue damage score (KTDS) were increased by IR. Urine volume, creatinine, and urea clearances decreased by IR. NaHS administration improved some parameters in males but exacerbated KTDS and serum markers related to renal function. Our data demonstrated that NaHS didn't protect female rats against renal IR injury. In males, it has null effects or just a few protective effects via antioxidant activity.