Malondialdehyde Levels In Rats Research Articles

Antioxidant In Reducing MDA Conditions and Increasing SOD Conditions in White Rats (Rattus norvegicus) Wistar Strain Given a High Cholesterol Diet and Induced More Physical Activity

Sedentary lifestyles increase the risk of morbidity and infectious illnesses. Physical exercise can improve immune function but can lead to increased oxidants and reactive oxygen species (ROS), damaging cells and tissues. Crucial in mitigating the cellular damage caused by free radicals are antioxidants, including non-enzymatic antioxidants such as glutathione, vitamins C and E, and others. Moderate to high-intensity physical exercise can result in an increase in ROS and a reduction in SOD. Grape seeds are rich in antioxidants, which have been shown to neutralize free radicals and protect against inflammation, bacteria, ulcers, and cancer. These antioxidants, including phenols and proanthocyanidins, are beneficial to health and have applications in various industries, including energy production, cosmetics, and pharmaceuticals. Research is also being conducted to explore their antioxidant effects on MDA levels. Grape seed extract was tested for its impact on malondialdehyde (MDA) levels in the blood of male Wistar strain white rats. Rats' MDA levels decreased following four weeks of treatment. Rat cages, digital scales, an MDA test kit, and SPSS were some of the equipment used in the study. Grape seed extract effectively reduces MDA levels in rats with hypercholesterolemia, resulting in weight loss and a lee index below 0.3, and increases SOD levels, indicating potential for human use.

Effects of Aerobic Exercise Along with Garlic Supplementation on Oxidative Stress and Sex Hormones in the Ovarian Tissue of Rats Under Wi-Fi Electromagnetic Radiation

Background: Electromagnetic radiation has different effects on body organs, including gonads and fertility. Information about the harmful impacts of Wi-Fi radiation on the oxidant-antioxidant system of ovarian tissue is limited. Objectives: Therefore, the present study aimed to evaluate the influence of eight weeks of aerobic exercise along with garlic supplements on the levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), and sex hormones in the ovarian tissue of rats under Wi-Fi electromagnetic radiation. Methods: This experimental study was performed on 40 Sprague Dawley female rats aged about 8 weeks. The animals were randomly divided into 5 groups: control, Wi-Fi radiation, aerobic exercise + Wi-Fi radiation, garlic supplement + Wi-Fi radiation, and aerobic exercise + garlic supplement + Wi-Fi radiation. Wi-Fi radiation was induced 1 h/day at a frequency of 2.45 GHz from a Wi-Fi modem. Endurance exercise was performed as three 60-minute sessions per week for 8 weeks with 50%-60% maximum running speed. Garlic supplement was given to rats for 8 weeks in drinking water at the dose of 800 mg/kg daily. Results: The results of this study showed that Wi-Fi radiation led to a decrease in the SOD and GPx levels, as well as an increase in the follicle-stimulating hormone (FSH) and MDA levels in rats (P ≤ 0.05). Moreover, garlic supplements diminished the FSH and MDA concentrations, as well as elevated the SOD levels in rats under Wi-Fi radiation. It was observed that aerobic exercise caused a decline in the FSH and MDA levels and a rise in the luteinizing hormone and SOD of the rats under Wi-Fi radiation. Furthermore, aerobic exercise along with garlic supplements reduced the FSH levels and augmented the SOD and GPx concentrations in rats under Wi-Fi radiation (P ≥ 0.05). Conclusions: According to the findings of the present study, aerobic exercise and garlic supplements both have lowering effects on oxidative stress and synergistically increase antioxidants. In addition, aerobic exercise and garlic supplements alone improve the sex hormones of rats exposed to Wi-Fi radiation.

Effect of Energy Restriction on Malondialdehyde Levels in Rats

Elevated malondialdehyde (MDA) levels indicate the occurrence of cell membrane oxidation. Calorie restriction is known to extend life expectancy. This study aims to investigate the effect of calorie restriction on MDA levels in young and old rats. An experimental approach was employed using Rattus norvegicus Wistar strain as the experimental animals, with a pre-post-test control group design. A total of 28 white rats were included in this study and were divided into four groups. The control groups, Group A and Group B, received standard feed and unrestricted access to distilled water, while the treatment groups, Group C and Group D, were fed with a 40% reduction in calorie intake and distilled water. Data analysis was performed using SPSS 21.0 (SPSS, Inc., Chicago, IL) with a 0.05 significance level. The results showed a difference in MDA level changes between group B (control group) and group D (treatment group) (p<0.05). This study concludes that MDA levels are higher in the elderly compared to young rats, and a 40% calorie restriction can reduce MDA levels.

Asetaminofenin indüklediği nefrotoksisiteye karşı montelukastın önleyici etkisi: Deneysel bir çalışma

Objective: Montelukast, an asthma drug, has an anti-inflammatory effect on tissues. We aimed to investigate therapeutic effect of montelukast (MK) on acetaminophen (APAP) - induced renal damage in rat models. Material and Methods: Twenty-four rats were randomly divided into four groups of six animals each. APAP was administered intraperitoneally as a single dose of 1000 mg/kg/day. In the treatment group, MK dose was 10 mg/kg and administered by oral gavage after APAP. The other groups were APAP + Saline group and the control group. We measured tissue malondialdehyde (MDA), reduced glutathione (GSH), and Nitric oxide (NO) levels to determine the nephrotoxicity. Results: Serum Blood Urea Nitrogen (BUN) and creatinine levels were measured significantly higher in APAP group than rats in the control and APAP + MK groups. The level of GSH was significantly diminished in APAP-treated rats. However, the administration of MK significantly increased the level of GSH in the MK treatment group. Tissue MDA levels in rats treated with APAP alone were significantly higher compared to the control group and APAP + MK group. The level of NO was measured as elevated in APAP treated group. However, NO levels in the MK treatment group were significantly lower than APAP treated group. Furthermore, some morphological recoveries were observed in the MK treatment group compared to APAP alone group. Conclusion: MK has beneficial effects on APAP-induced renal toxicity and dysfunction. However, clinical studies are needed to demonstrate appropriate use and effects. Keywords: acetaminophen, kidney, montelukast, nephrotoxicity, oxidative stress

The Effect of Red Ginger Extract on Tnf-α and Malondialdehyde Serum Level

Pseudomonas aeruginosa is the main pathogen causing nosocomial infections in hospitals, also can infect open wounds, combustio and necrotizing pneumonia. Several plant studies show the presence of antioxidants, one of them is red ginger. Research shows that red ginger extract contains the bioactive components gingerol and shogaol which have antioxidant and antimicrobial properties. The purpose of this research is to determine the effect of red ginger extract on TNF-α and serum malondialdehyde levels in rats infected with Pseudomonas aeruginosa bacteria. This study uses an experimental research design with Post Test Only Control Group Design. The research subjects were 30 wistar rats which were randomly divided into 5 groups. K (-) group of mice without P.aeruginosa infection. K(+) group of rats infected with P. aeruginosa 108 CFU per head without red ginger extract. P1, P2 and P3 were infected with P.aeruginosa and were given red ginger extract at a dose of 20mg, 40mg and 80mg/KgBB/day for 7 days. Day 8 examination of TNF-α and MDA levels. The results of the One Way Anova test showed a significant difference in TNF- levels and MDA levels with p value = 0.000. The mean levels of TNF- in groups K(-), K(+), P1, P2, P3 were 5.76, 17.89, 12.29, 9.03, 7.07 and the mean MDA levels were 1.33, 11.10, 5.09, 3.87, 3.00. Tukey's test results showed TNF-α levels between groups had a significant difference in all groups (p=0.000) and a significant difference also in MDA levels (P=0.000). Red ginger extract had an effect on decreasing TNF-α and serum MDA levels in rats infected with Pseudomonas aeruginosa.

The effect of glucagon like peptide-1 receptor agonist on behavioral despair and anxiety-like behavior in ovariectomized rats: Modulation of BDNF/CREB, Nrf2 and lipocalin 2

Ovariectomized (OVX) rodents show behavioral despair and anxiety-like behaviors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) possess neuroprotective effects by reducing oxidative stress and neuroinflammation, thereby preventing synaptic loss. The objective of the present study is to evaluate the effect of GLP-1RA, namely liraglutide, on emotional behaviors, and to identify the level of oxidative stress, neuroinflammation, and BDNF signaling in the hippocampus of OVX rats. Forty female young Wistar rats were divided into 5 groups: Control, Control+liraglutide treated, OVX, OVX+fluoxetine, and OVX+liraglutide (150 µg/kg for 15 days, sc). Open field test and elevated plus-maze test were used to evaluate behaviors that are suggestive of anxiety. A forced swimming test was used to evaluate behavioral despair. At the end of the experiments, blood glucose level and body weight gain were measured. The levels of BDNF, CREB, Nrf2, and lipocalin 2 in the hippocampal tissue were measured by ELISA. Malondialdehyde (MDA) and glutathione levels were also evaluated. Statistical analysis was conducted through ANOVA and Bonferroni tests. Seven weeks post-OVX rats exhibited high anxiety related behavior and behavioral despair in comparison with the control groups. These behavioral changes were associated with increased lipocalin 2 and MDA levels in rats. Moreover, BDNF, CREB, and Nrf2 levels decreased significantly in the hippocampus of OVX rats. Liraglutide treatment limited the reduction of BDNF and Nrf2 levels in the hippocampus, maintaining them at the control levels. Liraglutide treatment also prevented the symptoms of behavioral despair and anxiety related behavior. As the main finding of the study GLP-1RA reduced behavioral despair and anxiety level and this may be related to the preservation of BDNF/Nrf2 levels and the decrease in oxidative stress and lipocalin 2 levels in the hippocampus.

Investıgatıon of Lipid Profile, Malondialdehyde, Sodium, Potassium, Chloride Levels in Rats with Weight Loss

The aim of the fight against obesity is weight loss. Sometimes, the damage caused by weight loss can be ignored rather than its benefits. This situation; Sometimes, shock diet or excessive exercise can lead to unwanted consequences that can lead to sudden death. The purpose of our study; to examine changes in lipid profile, malondialdehyde levels in rats we have created weight loss. Also, it is to investigate changes in sodium and potassium chloride levels, which are of great importance inside and outside the cell. Twenty rats were used in the study. We randomly divided them into two groups. We exercised rats for 10 days. Triglyceride, cholesterol, (high-density-lipoprotein)HDL-cholesterol, (low-density-lipoprotein)LDL-cholesterol, Malondialdehyde, sodium, potassium chloride levels were analyzed. Sodium(p=0.034), potassium(p=0.018) and LDL-cholesterol(p=0.004) levels of the group with high weight loss were lower than the other group, Malondialdehyde(p=0.005) levels were found to be higher. Weight loss correlates negatively with sodium(p=0.031), potassium(p=0.005), chloride(p=0.036), LDL-cholesterol(p<0.001), HDL-cholesterol(p=0.035) and cholesterol(p=0.001). Weight loss correlates positively with Malondialdehyde(p=0.001). Weight loss causes the desired decrease in lipid profile and an unwanted increase in Malondialdehyde levels. Also, weight loss correlates negatively with sodium, potassium, and chloride levels. Both oxidative stress and electrolyte balance disorders can be life-threatening.

Effect of the Ethanol Extract of Mimosa Leaves on the Blood Glucose, Malondialdehyde, and Histopathological Characteristics of Wistar Rats

BACKGROUND: Hyperglycemia, a condition characterized by high blood glucose levels, is one of the hallmarks of type 2 diabetes mellitus. AIM: This study aimed to (1) determine if the ethanol extract of Mimosa leaves could lower blood glucose levels in Wistar rats with hyperglycemia and (2) identify the components of active compounds with antihyperglycemic properties. METHODS: In the blood glucose level reduction test, Wistar rats were used as an animal model of diabetes induced by streptozotocin. Blood glucose levels were measured using a glucometer, and active compounds were identified through Liquid Chromatography with tandem mass spectrometry (LCMS/MS). RESULTS: Results showed that the ethanol extract of Mimosa pudica leaves might significantly lower the blood glucose, and malondialdehyde levels of rats with hyperglycemia at 150 mg/kg BB (p &lt; 0.05). LCMS/MS analysis revealed that the ethanol extract of Mimosa leaves likely contained seven compounds that could decrease blood glucose and malondialdehyde levels: DL-valine, indoline, 2-quinolinol, trans-anrthole, luteolin, apigenin, linoliamide, and luteolinin. CONCLUSION: Histophatological determination with HE staining for pancreas.

Hylocereus polyrhizus effect on catalase and malondialdehyde in rats with oxidative stress

The excessive production of free radicals causes oxidative damage and degenerative diseases. Whereas, catalase is a macromolecule with a specific activity, but Malondialdehyde (MDA) is a small molecule with no activity. The peels of red dragon fruit (H. polyrhizus) are potential to be natural exogenous antioxidants. This research aimed to determine the effects of methanol fraction from H. polyrhizus peels on catalase activity and MDA level. The peel was macerated using chloroform and fractionated using methanol. The stress condition was done through five-day fasting and ten-minute swimming per day. The activity of catalase and MDA was measured using UV-Vis spectrophotometer. Thirty five rats were divided into 7 groups: normal, negative, dose I (5 mg/200gBW), dose II (10 mg/200gBW), dose III (20 mg/200gBW), positive control (quercetin) (4 mg/200gBW) and vitamin E (17.64 mg/kg). The activity of catalase in the normal, negative, vitamin E, and quercetin, dose I, II, and II respectively were: 28.37; 7.8; 24.85; 34.33; 59.92; 28.18; and 70.85 Unit/mL. The average MDA level in the groups respectively were: 0.042; 0.051; 0.034; 0.042; 0.037; 0.033; 0.030 μg/mL. The result of One Way ANOVA test showed that the catalase activity in dose III was significantly different than normal group; the MDA levels in all groups were significantly different than normal group. This research revealed that methanol fraction from H. polyrhizus peels is a potent antioxidant for its capacity to increase the activity of catalase and reduce the MDA level in rats with oxidative stress.

Evaluation of Therapeutic Efficacy of Stigma and Petal Extracts of Crocus sativus L. on Acetic Acid-Induced Gastric Ulcer in Rats

Saffron (Crocus sativus L.) has long been considered a medicinal plant in Traditional Persian Medicine (TPM) due to its therapeutic properties. Despite this interest, its effects on gastrointestinal disorders have not been completely taken into consideration. Hence, this study aimed to evaluate the pharmacological activity of ethanolic extracts of saffron stigma (SS) and saffron petal (SP) in acetic acid-induced gastric ulcer in rats. The gastric ulcer model was imitated by the serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed with 100 mg/kg and 200 mg/kg of ethanolic extracts of SS or SP, omeprazole (40 mg/kg), or saline for 12 days. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. The highest anti-ulcer activity was observed in the omeprazole-treated animals with the lowest ulcer size (4.29 ± 1.78 mm2). SS could not reduce gastric ulcer size in rats. Compared to the untreated rats, SP treatment significantly decreased ulcer indices in a dose-dependent manner. The gastric levels of PGE2, VEGF, and MDA were significantly elevated in the untreated animals with gastric ulcers compared to rats in the control group. The SS extract suppressed the elevated PGE2 and VEGF levels at both doses, while SP did not have a significant influence. Both SS and SP treatments significantly ameliorated MDA levels in rats with gastric ulcers. Omeprazole treatment enhanced the PGE2 level and suppressed MDA contents, but it did not influence the VEGF level. In conclusion, our findings demonstrated that the saffron stigma has no significant effects on the gastric ulcer healing process, while its petals accelerate the process. This discrepancy can be attributed to the difference in the main secondary metabolites between saffron stigma and petals.

Therapeutic potential of Ferula foetida(Bunge) Regel on gastric ulcer model in rats.

The plant Ferula foetida(Bunge) Regel (FFBR) has a long history in Asian traditional medicine. This study aimed to evaluate the ulcer healing potential of FFBR umbel ethanolic extract on acetic acid-induced chronic gastric ulcer in rats. First, the gastric ulcer model was imitated by serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed by ethanolic extract of FFBR umbel (100 mg/kg, 200 mg/kg, and 300 mg/kg), omeprazole (40 mg/kg), or saline for 12 days. Eventually, on the 13th day, animals were sacrificed, and their stomachs were taken out. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. In addition, the expression of NF-κB p65 was investigated by immunohistochemistry. Compared to the untreated rats with gastric ulcer, FFBR extract significantly decreased ulcer area even superior to omeprazole in a dose-dependent manner. Moreover, histological examination revealed that the extract (300 mg/kg) accelerated the epithelialization and differentiation of proliferative cells to mucosal tissue. The FFBR extract (300 mg/kg) increased tissue levels of VEGF and PGE2, but it did not affect MDA levels in rats with gastric ulcers. FFBR treatment (all doses) could significantly inhibit the expression of NF-κB p65 in gastric tissue. Taken together, experimental findings suggested that FFBR could accelerate the healing process of gastric ulcers in rats through mediating NF-κB and VEGF/PGE2 pathways.

Uji Efek Antioksidan Formulasi Sediaan Sirup Ekstrak Etanol Kulit Buah Jeruk Bali (Citrus Maxima Merr.) Terhadap Malondialdehid Tikus Putih (Rattus Novergicus) Yang Diinduksi Karbon Tetraklorida

Free radicals are any molecule or atom that is unstable because it has one or more unpaired electrons. Free radicals that are formed in the body will produce new free radicals through a chain reaction which eventually increases in number and attacks the body's cells so that tissue damage will occur, therefore antioxidants are needed from outside to neutralize free radicals, the salute is grapefruit peel (Citrus maxima Merr.) This study aims to determine the antioxidant activity of the ethanol extract syrup of grapefruit peel against levels of Malondialdehyde (MDA) blood plasma of male white rats induced by carbon tetrachloride (CCl4). The stages of this study were the first to make a skin extract syrup. grapefruit peel containing 1% extract (F1), 2% extract (F2), 3% extract (F3), and without grapefruit peel extract (F4) as negative control; Furthermore, testing the stability of the syrup preparations before and after storage was accelerated for 12 cycles, and finally the syrup with the best stability was tested for its lipid peroxidation inhibition activity in vivo with blood plasma MDA levels in rats induced by Carbon Tetrachloride. The results showed the results of the syrup stability test. indicates that F3 has the best stability. As for the in vivo test results, F3 showed a decrease in the MDA level of blood plasma in rats which was significantly different from the negative control. The grapefruit peel significantly decreased the MDA level of the rat blood plasma with a value p&lt;0.05. Keywords : Free radicals, Grapefruit Peel, Antioxidant, Syrup Preparation, Malondialdehyde (MDA)

Effect Of Roselle Petal Extract On Decreased Levels Of Mda In Rats With Type 2 Diabetes

Introduction: Diabetes mellitus type 2 is a metabolic disorder, namely a decrease in peripheral tissues' response to insulin. Free radicals increase, which results in the forming of Malondialdehyde (MDA). Roselle flower petals is an antioxidant to reduce free radical damage. Purpose: This study aims to analyze the effect of roselle petal extract on decreased MDA levels in mice induced by diabetes. Method: The rats were divided into four treatments group as follow: 1) control negative, 2) control positive, 3) treatment dose I (administering roselle petal extract 195 mg/200 gram body weight), 4) treatment dose II (giving roselle petal extract 260mg/ 200 gram body weight). MDA levels were measured using Thiobarbituric acid (TBA) assay. Result: There was an effect of rosella petal extract in the group with 260 mg/200 of rosella petal extract (p=0.005) and 195 mg/200 of rosella petal extract (p=0.041) compared with the positive control group. Conclusion: rosella petal extract significantly reduces MDA levels in rats induced by type 2 diabetes.

Effects of high fructose diet on lipid metabolism and the hepatic NF-κB/ SIRT-1 pathway

ABSTRACT The liver is the primary site for fructose metabolism; therefore, the liver is susceptible to fructose related metabolic disturbances including metabolic insulin dysfunction, dyslipidemia and inflammation. We investigated whether astaxanthin (ASX) can modify hepatic nuclear factor-kappa B (NF-κB)/sirtuin-1 (SIRT-1) expression to alter oxidative stress caused by ingestion of excess fructose in rats. The animals were divided randomly into two x two factorially arranged groups: two regimens were given either water (W) or 30% fructose in drinking water (F). These two groups were divided further into two subgroups each: two treatments, either orally with 0.2 ml olive oil (OO) or 1 mg ASX/kg/day in 0.2 ml olive oil (ASX). Fructose administration increased serum glucose, triglycerides and very low density lipoproteins, and decreased serum concentration of high density lipoproteins; fructose did not alter serum total cholesterol. Excess fructose decreased hepatic superoxide dismutase (SOD) and increased hepatic NF-κB and MDA levels. ASX treatment increased hepatic SIRT-1 and decreased hepatic NF-κB and malondialdehyde (MDA) levels. ASX treatment decreased hepatic NF-κB and increased SOD levels, but did not alter MDA level in rats fed high fructose. ASX administration ameliorated oxidative stress caused by excess fructose by increasing hepatic NF-κB and SIRT-1 expression.

Ethanol extract of Vitellaria paradoxa (Gaertn, F) leaves protects against sodium arsenite - induced toxicity in male wistar rats.

The inadvertent exposure to arsenic has been associated with diverse diseases such as cancers. Vitellaria paradoxa is a medicinal plant with antidiabetic and antiproliferative properties. Here, we assessed the ameliorative role of Ethanol Leaf extract of Vitellaria paradoxa (ELVp) in Sodium Arsenite (SA) - induced toxicity in rats after oral treatment for two weeks as follows: Group 1 (Control, distilled water), Group 2 (Vitamin E, 100 mg/kg), Groups 3 and 4 (ELVp, 100 & 200 mg/kg respectively), Group 5 (SA, 2.5 mg/kg), Group 6 (SA + Vit E) and Group 7 (SA + ELVp (100 mg/kg) and Group 8 (SA + ELVp (200 mg/kg). The results indicated that SA significantly increased liver and kidney function markers and elevated platelet, white blood cell (WBC) count and malondialdehyde levels in rats. Additionally, SA decreased Red Blood Cell (RBC), Hemoglobin (HGB) and Hematocrit (HCT) levels in rats (p < 0.05). Sodium arsenite caused mild expression of BCL-2 protein> NF-Kb = p53 in the kidney of rats. However, ELVp ameliorated SA-induced toxicity in the liver and kidney of rats with respect to these markers. Overall, ELVp has hepatoprotective, nephroprotective and apoptotic properties against sodium arsenite-induced toxicity.

Effect of natron administration on the antioxidant status and lipid profile of rats.

Natron consumption has been implicated in the pathogenesis of peripartum cardiomyopathy. This work evaluates the effect of natron on the antioxidant status and lipid profile of postpartum rats administered graded doses of natron for four consecutive weeks. After treatment, the rats were assessed for antioxidant status, malondialdehyde level, and lipid profile. The results revealed that natron caused a significant decrease (P˂0.05) in the activity of catalase in rats administered with 300mg/kgofnatroncomparedto control. The activities of superoxide dismutase and glutathione peroxidase decreased in a dose-dependent manner; however, the difference was not statistically significant when compared with control. Serum levels of antioxidant minerals were also significantly decreased (P˂0.05) at higher doses of natron in comparison to control. There was a significant increase (P<0.05) in the malondialdehyde level in rats administered with 200 and 300mg/kg of natron when compared with control. Natron at higher doses caused a significant increase (P˂0.05) in the level of the lipid profile parameters except for high-density lipoprotein-cholesterol that decrease significantly (P˂0.05). This study demonstrated that the administration of natron at high doses induced dyslipidemia and oxidative stress in postpartum rats. PRACTICAL APPLICATION: This research reports the implication of a high intake of natron to health and to establish the relationship between natron intake and peripartum cardiomyopathy (PPCM) using an animal model. Natron has health benefits; however, its consumption at high doses should be discouraged as it can lead to oxidative stress (OS) and dyslipidemia. The results suggest that OS due to natron may contribute to the pathogenesis of PPCM. A high concentration of natron can be used to induce an animal model of PPCM, which would be of practical application in studying the molecular basis and possible discovery of therapeutics for the disease.

Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats.

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney’s relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats’ blood and malondialdehyde levels in rats’ urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood’s antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons’ histology from cisplatin’s toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.

Ulinastatin protects rats with myocardial infarction by activating Nrf2/NOS pathway.

The aim of the study was to explore the pharmacological role of ulinastatin in rats with myocardium infarction (MI) and its underlying mechanism. Rats were randomly assigned into sham group, MI group, and ulinastatin group, with 8 rats in each group. MI model in rats was constructed and specific drug administrations were performed in each group. Electrocardiogram and hemodynamics were detected before and after animal procedures. Myocardium function in rats was accessed by determining serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Hematoxylin and eosin (HE) staining was performed to detect the infarct area in rat myocardium. Terminal Deoxynucleotidyl Transferase dUTP Nick-end Labeling (TUNEL) assay was conducted to calculate the ratio of apoptotic cells in rat myocardium. Subsequently, relative oxidative stress indicators in rats were accessed, including total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), Superoxide Dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS). Western blot was conducted to detect protein levels of nuclear factor E2-related factor 2 (Nrf2), Nuclear Factor κB (NF-Κb), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in rat myocardium. No significant differences in heart rate, the voltage of the QRS wave and Q-T interval were observed among rats in sham group, MI group, and ulinastatin group prior to the animal procedures. However, at the end of the animal procedures, rats in ulinastatin group showed higher heart rate and voltage of QRS wave, as well as shorter Q-T interval than those in MI group. Rats in ulinastatin group presented lower serum levels of CK-MB and LDH compared with those in MI group, whereas they did not return to baseline. Rats in ulinastatin group showed higher levels of LVSP, dP/dtmax, LVEDP, and -dP/dtmax than those in MI group. Larger infarct area was observed in MI group compared with that of sham group, whereas ulinastatin treatment remarkably reduced the infarct area. HE staining showed remarkable pathological lesions in MI rats, whereas ulinastatin group showed milder lesions in rat myocardium. TUNEL assay showed fewer TUNEL-positive cells in ulinastatin group than those of MI group. Levels of T-AOC, CAT, GSH, and SOD were remarkably higher in myocardium homogenate of MI group than sham group, whereas ulinastatin treatment significantly decreased these levels. Ulinastatin group showed less ROS accumulation and decreased MDA level in rats than those of MI group. Ulinastatin treatment upregulated Nrf2, HO-1, and NQO1, whereas downregulated NF-κB expression. Ulinastatin protects MI rats by inhibiting inflammatory response through activating Nrf2/NOS pathway.

Protective effect of α-terpineol against impairment of hippocampal synaptic plasticity and spatial memory following transient cerebral ischemia in rats.

Cerebral ischemia is often associated with cognitive impairment. Oxidative stress has a crucial role in the memory deficit following ischemia/reperfusion injury. α-Terpineol is a monoterpenoid with anti-inflammatory and antioxidant effects. This study was carried out to investigate the effect of α-terpineol against memory impairment following cerebral ischemia in rats. Cerebral ischemia was induced by transient bilateral common carotid artery occlusion in male Wistar rats. The rats were allocated to sham, ischemia, and α-terpineol-treated groups. α-Terpineol was given at doses of 50, 100, and 200 mg/kg, IP once daily for 7 days post ischemia. Morris water maze (MWM) test was used to assess spatial memory and in vivo extracellular recording of long-term potentiation (LTP) in the hippocampal dentate gyrus was carried out to evaluate synaptic plasticity. Malondialdehyde (MDA) was measured to assess the extent of lipid peroxidation in the hippocampus. In MWM test, α-terpineol (100 mg/kg, IP) significantly decreased the escape latency during training trials (P<0.01). In addition, α-terpineol increased the number of crossings over the platform location and decreased average proximity to the target in probe trial (P<0.05). In electrophysiological recording, α-terpineol (100 mg/kg) facilitated the induction of LTP in the hippocampus which was persistent over 2 hr. α-Terpineol (100 and 200 mg/kg) also significantly lowered hippocampal MDA levels in rats subjected to cerebral ischemia. These findings indicate that α-terpineol improves cerebral ischemia-related memory impairment in rats through the facilitation of LTP and suppression of lipid peroxidation in the hippocampus.

Protective effects of Chaenomeles thibetica extract against carbon tetrachloride-induced damage via the MAPK/Nrf2 pathway.

Chaenomeles thibetica, a type of fruit of the genus Chaenomeles, is commonly cultivated and used as Mugua in China and as liquor, candy, and functional food in Tibet. Total phenol, flavonoid, and proanthocyanidin contents were measured in C. thibetica extract (CTE). CTE had a positive effect on free radical scavenging and anti-lipid oxidation in vitro. The protective effects of CTE against carbon tetrachloride (CCl4)-induced oxidative damage in vivo were also measured. The results of antioxidative enzymes indicated that CTE can increase the activities of the catalase, superoxide dismutase, and glutathione contents and reduce the level of malondialdehyde in rats. The levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and total bilirubin were significantly reversed by CTE compared with the elevated levels in the CCl4 group. Besides, CTE could reverse the cell viability of HepG2 inoculated with CCl4via phosphorylation of mitogen-activated protein kinases (MAPKs), activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increasing the expression of phase II detoxification enzymes. These effects may expand the applications of C. thibetica and offer alternative food with antioxidant and hepatoprotective functions in the food industry.