Tissue Malondialdehyde Levels Research Articles

Effect of extracts of dialium guineense stem bark on lipid peroxidation index and histological changes in kidneys of normal rats

Aim: To investigate the effect of extracts of Dialium guineense stem bark on lipid peroxidation index and histological changes in kidneys of normal rats. Materials and Methods: Adult male Wistar rats (n = 70; 35 rats per extract) weighing 160 to 180 g were divided into seven (7) groups of five (5) rats each. Group I served as control, while rats in the other groups were administered varied doses of extract (200 - 5000 mg/kg body weight, bwt) orally for a duration of 28 days. Tissue malondialdehyde (MDA) level was measured as well as histopathological assessment. Results: Percentage increases in body weights of rats treated with aqueous or ethanol extract of D. guineense stem bark were significantly reduced, when compared with control group (p< 0.05), but there were no significant differences in the corresponding relative organ weights and tissue MDA level among the groups (p> 0.05). Similarly, the extracts did not significantly alter the normal architecture of the kidney. Conclusion: The aqueous and ethanol extracts of the medicinal plant did not elicit any deleterious effects on rat kidney.

Antioxidant response of the oyster Crassostrea hongkongensis exposed to diel-cycling hypoxia under different salinities

Intertidal and estuarine bivalves are adapted to fluctuating environmental conditions but the cellular adaptive mechanisms under combined stress scenarios are not well understood. The Hong Kong oysters Crassostrea hongkongensis experience periodic hypoxia/reoxygenation and salinity fluctuations during tidal cycles and extreme weather, which can negatively affect the respiratory organs (gills) involved in oxygen uptake and transport. We determined the effects of periodic hypoxia under different salinities on the oxidative stress response in Hong Kong oysters. Oxidative stress parameters (activities of superoxide dismutase (SOD), and catalase (CAT), tissue levels of malondialdehyde (MDA) and protein carbonyl content (PCC)) were determined in the gills of oysters exposed to diel-cycling hypoxia (hypoxia at night: 12h at 2 mg/L, reoxygenation: 12h at 6 mg/L) and normal dissolved oxygen (DO) (6 mg/L) under three salinities (10, 25, and 35‰) for 28 days. Oxygen regime in combination with salinity changes had significant interactive effects on all studied parameters except SOD. Salinity, DO and their interactions increased PCC after 14 and 28 days of exposure, and the combination of hypoxia/reoxygenation and decreased salinity showed the most severe effect. MDA content of the gills increased only after the long-term (28 days) exposure in decreased or increased salinity under normal DO treatments, showing PCC was more sensitive than MDA as biomarker of oxidative stress. Low salinity suppressed SOD activity regardless of the DO, whereas hypoxia induced SOD responses. CAT activities decreased significantly under high salinity with hypoxia/reoxygenation conditions. Our findings highlighted that periodic hypoxia/reoxygenation with salinity change induced antioxidant responses, which can impact the health of Hong Kong oyster C. hongkongensis and prolonged salinity stress may be one reason for the mortality during its aquaculture process.

Glyphosate-induced liver and kidney dysfunction, oxidative stress, immunosuppression in Nile tilapia, but ginger showed a protection role

The water-borne herbicides are involved in the toxicity of aquatic animals resulting in impaired health status and low productivity. Dietary medicinal herbs present a practical solution to relieve the impacts of herbicides toxicity on the performances of aquatic animals. Herein, we investigated the toxicity of commercial glyphosate-induced oxidative stress, immunosuppression, liver and kidney dysfunction, and the protective role of ginger or ginger nanoparticles in Nile tilapia. Fish were allocated into four groups: the first group presented the control without glyphosate toxicity and ginger feeding, the second group intoxicated with glyphosate at 0.6 mg/L and fed ginger free diet, the third group intoxicated with glyphosate and fed ginger at 2.5 g/kg, and the fourth group intoxicated with glyphosate and fed ginger nanoparticles at 2.5 g/kg. Fish were kept under the experimental conditions for four weeks, and the samples of blood and tissues were collected after 2 and 4 weeks. Markedly, fish exposed to glyphosate showed the highest ALT and AST activities, glucose and cortisol levels, and malondialdehyde levels (MDA) in gills and tissues. While fish in the control and fish intoxicated with glyphosate and fed ginger nanoparticles had the lowest ALT and AST activities, glucose and cortisol levels, and MDA levels after 2 and 4 weeks (P < 0.05). Fish fed dietary ginger had lower ALT and AST activities, glucose and cortisol levels, and MDA levels than the glyphosate intoxicated group after 2 and 4 weeks (P < 0.05). Interestingly, fish-fed ginger nanoparticles showed lower urea and creatinine levels and higher total protein, albumin, and globulin than the glyphosate intoxicated group (P < 0.05) and similar to the control (P > 0.05). Further, fish intoxicated with glyphosate and fed ginger nanoparticles had the highest GSH, lysozyme activity, and immunoglobulin levels after 2 and 4 weeks (P < 0.05). In conclusion, ginger nanoparticles are superior to the standard ginger form in enhancing the antioxidative and immune responses of Nile tilapia exposed to glyphosate.

Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells.

Acute kidney injury (AKI) represents a prevailing complication of sepsis, and its onset involves ferroptosis. Ginsenoside Rg1 exerts a positive effect on kidney diseases. This study explored the action of ginsenoside Rg1 in sepsis-induced AKI (SI-AKI) by regulating ferroptosis in renal tubular epithelial cells (TECs). Sepsis rat models were established using cecal ligation and puncture (CLP) and cell models were established by treating human renal TECs (HK-2) with LPS to induce ferroptosis. Serum creatinine (SCr) and blood urea nitrogen (BUN) and urine KIM1 contents in rats were determined by ELISA kits. Kidney tissues were subjected to immunohistochemical and H&E stainings. Iron concentration, malondialdehyde (MDA), glutathione (GSH), and ferroptosis-related protein (ferritin light chain [FTL], ferritin heavy chain [FTH], GSH peroxidase 4 [GPX4], and Ferroptosis suppressor protein 1 [FSP1]) levels in kidney tissues and HK-2 cells were measured using ELISA kits and Western blotting. HK-2 cell viability was detected by cell counting kit-8, and cell death was observed via propidium iodide staining. Reactive oxygen species accumulation in cells was detected using C11 BODIPY 581/591 as a molecular probe. In CLP rats, ginsenoside Rg1 reduced SCr, BUN, KIM1, and NGAL levels, thus palliating SI-AKI. Additionally, ginsenoside Rg1 decreased iron content, FTL, FTH, and MDA levels, and elevated GPX4, FSP1, and GSH levels, thereby inhibiting lipid peroxidation and ferroptosis. Moreover, FSP1 knockdown annulled the inhibition of ginsenoside Rg1 on ferroptosis. In vitro experiments, ginsenoside Rg1 raised HK-2 cell viability and lowered iron accumulation and lipid peroxidation during ferroptosis, and its antiferroptosis activity was dependent on FSP1. Ginsenoside Rg1 alleviates SI-AKI, possibly resulting from inhibition of ferroptosis in renal TECs through FSP1.

Relaxin and Erythropoietin Significantly Reduce Uterine Tissue Damage during Experimental Ischemia-Reperfusion Injury.

Successful uterus transplantation, a potential treatment method for women suffering from absolute uterine infertility, is negatively affected by ischemia–reperfusion injury (IRI). The aim of this study is to investigate the protective effect of relaxin (RLX) or/and erythropoietin (EPO) on experimental uterus IRI. Eighty rats, randomly assigned into eight groups (n = 10/group), were pretreated with either saline, 5 μg/kg human relaxin-2, 4000 IU/kg recombinant human erythropoietin or their combination. Ischemia was achieved by clamping the aorta and ovarian arteries for 60 min, following 120 min of reperfusion and tissue sampling. For sham animals, clamping was omitted during surgery. There were no differences in tissue histological score, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, myeloperoxidase (MPO) and TUNEL-positive cell count between all sham-operated rats. Pretreatment with RLX preserved normal tissue morphology, reduced MDA levels, MPO and TUNEL-positive cell count, preserved SOD activity and upregulated NICD and HES1 gene expression when compared to the control group. Pretreatment with EPO reduced MDA levels. In conclusion, pretreatment with RLX, EPO or a combination of both EPO and RLX significantly alleviates uterine tissue damage caused by IRI.

The Healing Effect Of Digoxin On Peripheral Nerve Damage and Its Relation to IL-17/IL-10.

Peripheral nerve damage mainly develops after mechanical trauma, and microenvironment impairment after damage delays the healing process. Additionally, digoxin is a glycoside with proven anti-inflammatory activity. Thus, this study aimed to demonstrate the curative effect of digoxin on peripheral nerve damage with its anti-inflammatory role on interleukin (IL)-17. The study was conducted with 30 male Sprague Dawley albino mature rats, of which 10 formed the control group, 10 were surgically treated and administered saline (group S), and another 10 were surgically treated and administered digoxin (group D). Motor functions and immunohistochemical and biochemical variables of the rats were assessed after therapy. The amplitude of the inclined plane test scores and the compound muscle action potential levels were greater in group D than in group S. Likewise, there were higher nerve growth factor percentages, higher axon counts, and lower fibrosis score percentages in group D than is group S. Lastly, lower tissue malondialdehyde and plasma IL-17 levels were determined in group D, while the IL-10 level was higher. Digoxin contributes to nerve healing and neuroprotective effect by demonstrating its anti-inflammatory effect on IL-17. It can be considered an adjunctive therapy for peripheral nerve injury.

Morinda lucida stem bark reversed the pattern and extent of lead nitrate-induced liver injury in Wistar rats

Lead toxicity remains one of the most important occupational and environmental health problems with characteristic features that are incompatible with life. Considering the foregoing, we investigated the ameliorative potentials of Morinda lucida stem bark (MLSB) extract on lead nitrate-induced hepatic injury with particular emphasis on its effects on the pattern and extent of lead nitrate toxicity. Thirty-six adult Wistar rats were randomly assigned into six groups (n=6). Normal control group received 2.2mL/kg distilled water only for 4 weeks while hepatic injury was induced by 2-week oral administration of 30mg/kg lead nitrate to experimental rats in the remaining five groups. Following induction, test groups were treated with MLSB for another 2 weeks at 100, 250, and 500mg/kg concentrations respectively while silymarin was administered orally for 2 weeks to positive control group. At the end of the study, serum activities of liver function enzymes and tissue levels of malondialdehyde were determined. Patterns and extent of injury were determined in hematoxylin and eosin-stained section. The result revealed a significant reduction in sera levels of liver function enzymes and tissue level of malondialdehyde (MDA) in extract treated groups. Lead nitrate-induced necrotic changes and other deranged features observed in histological sections were multifocal and they span through multiple zones of hepatic acini (panacinar), MLSB at 250mg/kg concentration reversed by some of these effects. The study concluded that ameliorative property of MLSB could be due to the antioxidant and membrane stabilizing properties of its phenolic compounds.

Vitamin E Suppresses Aortic Ultrastructural Alterations Induced by Toxic Doses of Monosodium Glutamate

An association between certain food additives and chronic diseases is reported. Current study determined whether administering toxic doses of the food additive monosodium glutamate (MSG) into rats can induce aortopathy in association with the oxidative stress and inflammatory biomarkers upregulation and whether the effects of MSG overdose can be inhibited by vitamin E. MSG at a dose of (4 mg/kg; orally) that exceeds the average human daily consumption by 1000x was administered daily for 7 days to the rats in the model group. Whereas, rats treated with vitamin E were divided into two groups and given daily doses of MSG plus 100 mg/ kg vitamin E or MSG plus 300 mg/kg vitamin E. On the eighth day, all rats were culled. Using light and electron microscopy examinations, a profound aortic injury in the model group was observed demonstrated by damaged endothelial layer, degenerated smooth muscle cells (SMC) with vacuoles and condensed nuclei, vacuolated cytoplasm, disrupted plasma membrane, interrupted internal elastic lamina, clumped chromatin, and damaged actin and myosin filaments. Vitamin E significantly protected aorta tissue and cells as well as inhibited MSG-induced tissue malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The highest used vitamin E dosage was more effective. Additionally, a significant correlation was observed between the aortic injury degree and tissue MDA, TNF-α, IL-6, and superoxide dismutase (SOD) levels (p=0.001). Vitamin E effectively protects against aortopathy induced by toxic doses of MSG in rats and inhibits oxidative stress and inflammation.

Protective role of vitamin D against radiation hazards in rats fed on high fat diet

BackgroundBoth exposure to ionizing radiation and obesity have been linked to a variety of diseases. As a result, there is an urgent need to consider the combined impact of these risks, as well as the role of vitamin D as an antioxidant. PurposeThe current study aims to explore the potential role of vitamin D against the harmful effects of gamma irradiation on lung and heart of obese rats. Materials and methods40 male albino rats were divided into 5 equal groups: (1) a normal group, (2) an obese group fed a high-fat diet, (3) a normal group exposed to a single dose of ɤ-radiation (6Gy) before the end of experiment by 24 h, (4) an obese group exposed to radiation at same time as group3, and (5) and obese group injected intramuscular by vitamin D in the last three weeks of experiment, three times by week and exposed to radiation at same time as “G3” and “G4”. ResultsThere was a significant increase in the serum level of lipid, inflammatory agent, creatine kinase myocardial band, troponin and tissue levels of malondialdehyde in lung and heart, while there was a decline in the tissue level of glutathione. This biochemical alternation was accompanied by histological changes in the heart and lung tissues in the gamma irradiation group and the obese groups compared to the normal group. While, supplementation of vitamin D decreases these harmful effects as well as protects the heart and lung tissue from the injurious effects of obesity and gamma irradiation. In conclusionvitamin D has a potential role as an antioxidant and anti-inflammatory agent, which highlights the significance of vitamin D supplementation to obese and oncology patients during radiotherapy to protect or at least alleviate the harmful effects of radiotherapy.

Anti-inflammatory, anti-oxidant and anti-apoptotic effects of olive leaf extract in cardiac tissue of diabetic rats.

Inflammatory process and apoptosis are involved in the pathogenesis of cardiac injury and oxidative damage caused by diabetes mellitus. The cardioprotective effects of standardized aqueous ethanolic olive leaf extract (OLE), metformin (as a cardiovascular protective agent) and valsartan (as an angiotensin receptor blocker) in the streptozotocin-induced diabetic rats were evaluated. Wistar rats divided into control, diabetic, OLE-treated (100, 200 and 400 mg/kg), metformin (300 mg/kg)-treated, valsartan (30 mg/kg)-treated and metformin/valsartan-treated diabetic groups. Biochemical parameters, including malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activates, and the total contents of thiol were measured, and histopathological and gene expression studies were done on cardiac tissues. Fasting blood sugar (FBS) and cardiac injury markers were examined in serum. FBS; the serum levels of lactate dehydrogenase (LDH), creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST); and heart tissue MDA levels due to diabetes were significantly alleviated by OLE treatment (effect size; ηp2 = 0.934, 0.888, 0.848, 0.888 and 0.879, respectively), and SOD and CAT activity and the thiol content in heart tissue were significantly increased (effect size; ηp2 = 0.770, 0.749 and 0.753, respectively). Interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and the number of infiltrating inflammatory cells were reduced in cardiac tissues of OLE-treated groups compared with the diabetic rats (effect size; ηp2 = 0.969 and 0.949, respectively). OLE up-regulated BCL2 gene expression and down-regulated BAX gene expression in cardiac tissue (effect size; ηp2= 0.490 and 0.522, respectively). OLE in a dose-dependent manner ameliorates cardiac damage in diabetic cardiomyopathy, perhaps through attenuating inflammation, oxidative stress and apoptosis.

Effects of losartan on glandular epithelial prostatic hyperplasia in spontaneously hypertensive rats

ABSTRACT Introduction Benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) are common disorders in aging men and cause lower urinary tract symptoms. Hypertension induces atherosclerosis in the blood vessels of the lower urinary tract, subsequently following by the development of BPH and BPE. Clinical study demonstrated that anti-hypertensive drug angiotensin II type 1 receptor blocker (ARB) treatment improved storage and voiding scores in male patients with hypertension, whereas other antihypertensive drugs were not effective. ARB could improve prostatic hyperplasia independent of reducing blood pressure. Spontaneously hypertensive rats (SHRs) are widely used as genetically hypertensive model. SHRs also demonstrate decreased prostatic blood flow and develop glandular epithelial hyperplasia and morphological abnormalities in the ventral prostate. Objective We examined the effects of an ARB, losartan on glandular epithelial prostatic hyperplasia in SHRs. Methods Thirty-six-weeks old male SHRs were orally treated with losartan (3 or 10 mg/kg/day) or vehicle once daily for 18 weeks. Wistar Kyoto rats (WKYs) were treated with vehicle were used as controls (n = 8). After the oral treatment, effects of losartan were evaluated by measuring prostate weight, blood pressure, and prostatic blood flow. The tissue levels of malondialdehyde (oxidative stress marker; MDA), interleukin-6 (inflammatory cytokine; IL-6), and basic fibroblast growth factor (bFGF) levels in ventral prostate were measured by colorimetric assay and ELISA assay. Histological analysis for the ventral prostate was performed by hematoxylin and eosin (HE) staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The glandular epithelial area was determined by HE staining. TUNEL assay was performed to quantify the degree of apoptosis. The statistical differences were determined using one-way analysis of variance followed by the Tukey-Kramer test. Histological data were analyzed using the nonparametric Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni's correction for multiple comparison. Results Body weight did not significantly differ among the groups. The vehicle treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow compared to the vehicle treated WKYs. Treatment with losartan significantly decreased PBR and improved prostatic blood flow and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs. Conclusion Chronic losartan treatment could improve glandular epithelial prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might improve not only hypertension but also prostatic hyperplasia in humans. Disclosure Work supported by industry: no.

Naringin attenuates oxidative stress, inflammation, apoptosis, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats

Objective: To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats. Methods: Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups. The control group was given intragastric (i.g.) saline (1 mL) for 10 d. The acrylamide group was given i.g. acrylamide in saline (38.27 mg/kg titrated to 1 mL) for 10 d. The treatment groups were administered with naringin in saline (50 and 100 mg/kg, respectively) for 10 d and given i.g. acrylamide (38.27 mg/kg) 1 h after naringin injection. The naringin group was given i.g. naringin (100 mg/kg) alone for 10 d. On day 11, intracardiac blood samples were obtained from the rats when they were under anesthesia, after which they were euthanized. Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer. Enzyme-linked immunosorbent assay was used to quantify malondialdehyde, superoxide dismutase, glutathione, glutathione peroxidase, catalase, tumor necrosis factor-β, nuclear factor-κB, interleukin (IL)-33, IL-6, IL-1β, cyclooxygenase-2, kidney injury molecule-1, mitogen-activated protein kinase-1, and caspase-3 in kidney tissues. Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2. Results: Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels. Naringin increased superoxide dismutase, glutathione, glutathione peroxidase, and catalase activities and decreased malondialdehyde levels in kidney tissues. In addition, naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues. The histopathological assay showed that acrylamide caused histopathological changes and DNA damage, which were ameliorated by naringin. Conclusions: Naringin attenuated inflammation, apoptosis, oxidative stress, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.

Aging exacerbates hypertension related testicular injury in rats

ABSTRACT Introduction The average age of paternity is rising in developed world. Hypertension is the most common chronic disease among adult males, affecting male fertility. Aging is an important risk factor for the development of atherosclerosis and hypertension. However, involvements of aging on hypertension related testicular injury are not fully clarified. Objective In this study, we investigated the involvements of aging on testes in spontaneously hypertensive rats (SHRs). Methods Male SHRs and Wistar Kyoto rats (WKYs; normotensive control) at the age of 36, 54 or 72 weeks (wk) were used (n=6, each age). At each age, body weight, testicular weight and blood pressure were measured. Serum testosterone and testicular tissue levels of malondialdehyde (MDA: a maker of lipid peroxide) were also measured by colorimetric assay and ELISA assay. Morphological changes in the testis were evaluated by hematoxylin and eosin staining. TUNEL staining was performed to quantify the apoptosis in testis. Results SHRs at 36, 54 o 72 wk showed a significant increase in mean blood pressure compared to WKYs at each age. SHRs at 54 or 72 but not 36 wk demonstrated a significant decrease in body weight and increase in testicular weight/body weight ratio compared to WKYs at each age. Testicular tissue levels of MDA in SHRs at all ages were significantly higher than those in WKYs at all ages. Serum testosterone in SHRs at 54 or 72 but not 36 wk was lower than that in WKYs at each age. SHRs at 54 or 72 but not 36 wk demonstrated obvious morphological changes such as thickening of blood vessel wall in testis, and seminiferous tubules with degeneration compared to the WKYs at each age. Number of TUNEL positive cells in testicular seminiferous tubules in SHRs at 36 wk was significantly greater than those in WKYs at 36 wk. While number of TUNEL positive cells in testicular seminiferous tubules in SHRs at 72 wk was significantly lower than those in WKYs at 72 wk. Conclusion Aged SHRs showed significant increases in oxidative damage and vacuolation in testes, and decrease in serum testosterone compared to age matched WKYs. Aging could exacerbate hypertension related testicular injury in rats. Disclosure Work supported by industry: no.

Potential Protective Effect of Zingiber officinale in Comparison to Rosuvastatin on High-fat diet-induced Non-alcoholic Fatty Liver Disease in Rats

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease affecting nearly 25% of adults worldwide with related risk factors including obesity, metabolic, and inflammatory diseases. Many therapeutic remedies of natural or synthetic properties were used. AIM: This study aimed to investigate and compare the effects of ginger/rosuvastatin (ROSU) on the liver of rats with induced NAFLD. MATERIALS AND METHODS: Forty adult male albino rats were used in this study and divided into four equal subgroups, Group I, control received the standard rat chow diet and given normal saline (1 ml/kg/day), Group II, high-fat diet (HFD) group, Group III, received HFD+ ROSU (15 mg/kg/day), and Group IV, HFD+ Zingiber officinale (10% W/V) for 6 weeks. At the end of our experiment, the rats were sacrificed then blood samples were collected for biochemical analysis of lipid profiles and liver enzymes, liver specimen was prepared for light and electron microscopic examination, and measurement of tissue level of malondialdehyde. RESULTS: NAFLD caused degenerative changes and lipid deposition in liver cells as evidenced by microscopic results and laboratory tests. Treatment with ginger/ROSU alleviated those changes. CONCLUSION: Ginger and ROSU could ameliorate liver functions in NAFLD and ginger effect is superior to ROSU.

Gastroprotective, hepatoprotective, and nephroprotective effects of thymol against the adverse effects of acetylsalicylic acid in rats: Biochemical and histopathological studies

Acetylsalicylic acid (Aspirin) has been used for a long time as an antipyretic and analgesic. Nevertheless, aspirin use is associated with severe morbidity and death because of its detrimental impacts on several organs, including the liver, kidneys, and stomach. The current investigation sought to ascertain the influence of thymol in mitigating aspirin-mediated gastric and hepato-renal injury. This was done by 1) evaluating gastric juice volume and pH as well as pepsin and prostaglandin E2 level; 2) measuring serum biochemical parameters and proinflammatory cytokines; 3) determining tissue oxidant/antioxidant status, and 4) identifying a link with gastric, hepatic and renal histopathological changes. Forty-eight rats were segregated to six groups: normal control, Th100, Th200, ASA, Th100 + ASA, Th200 + ASA. Daily administration of aspirin (ASA, 150 mg/kg body weight) for 3 successive days induced a significant increase in gastric juice volume, pepsin activity, serum transaminases, alkaline phosphatase, urea, creatinine, tumor necrosis factor-α, myeloperoxidase, and tissue malondialdehyde levels. In contrast, a significant reduction in gastric pH, prostaglandin E2, tissue non-enzymatic antioxidant (glutathione), and enzymatic antioxidant (superoxide dismutase, glutathione peroxidase, and catalase) levels. These biochemical changes were accompanied by histological modifications that included changes to the normal gastric, hepatic, and renal architectures. Pretreatment and simultaneous oral treatment with thymol (100 or 200 mg/kg body weight) plus ASA significantly improved all biochemical and histological changes in a dose-dependent way. Thymol's antiinflammatory and antioxidative properties may contribute to its protective action. As a result, thymol may represent a promising medication for preventing aspirin-induced gastric, liver, and renal damage.

Synthesis, spectral, and X-ray structural characterization of mixed tren-barbitone nickel(II) complex grafted g-C3N4 for oxidative stress and antioxidant activities

A new complex, [Ni(Tren)(Barb)(H2O)](Barb)(Barb-H)·2H2O (NiC) {Tren = tris(2-aminoethyl)amine and Barb = 5,5-diethlybarbiturate}, has been synthesized and characterized. The nickel(II) complex was grafted to g-C3N4, forming NiC@g-C3N4. The obtained NiC complex and its hybrid material NiC@g-C3N4 were characterized by FT-IR, TGA-DSC, UV–vis, SEM-EDX, and XRD. Single crystal X-ray crystallography shows that NiC exhibits NiN5O octahedral geometry. The results also show that the complex molecules are connected via N–H⋅⋅⋅⋅O hydrogen bonds. The complex NiC and NiC@g-C3N4 show oxidative stress effects on in vivo experiments. They also showed an increase in tissue damage markers that are represented by increase in tissue levels of malondialdehyde (MDA) in brain, liver, kidney and heart. Both materials showed inhibitory activity for examined antioxidants such as glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione (GSH) and glutathione reductase (GSH-R). The destructive effects were clearer for the NiC@g-C3N4 composite in liver, brain and kidney, respectively. The grafting of NiC complex in g-C3N4 is responsible for improving the catalytic activity of the compound, due to the synergistic effect of both components and facile recovery, as well recycling of the catalyst.

The healing effects of Ganoderma lucidum on intestinal ischemia-reperfusion damage in rats

Background/Aim: Intestinal ischemia-reperfusion (I/R) injury causes serious clinical problems and carries high morbidity and mortality risks. Ganoderma lucidum (GL) is known as an anti-inflammatory immunomodulator and antioxidant. This study aimed to investigate the curative effects of GL on intestinal I/R injury in rats. Methods: Twenty-four Wistar-Albino male rats were randomly divided into three groups. After 30/90 minutes of I/R, intestinal and hepatic tissue examples were histologically examined. Biochemical analysis, serum, intestinal and hepatic tissue malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were measured. Results: The I/R group had significantly elevated leukocyte, thrombocyte, serum, and intestinal and hepatic tissue MDA levels compared to the sham group (P < 0.05). Serum, intestinal tissue, and liver tissue SOD levels were significantly lower in the I/R group than in the control group (P < 0.05). In addition, GSH-Px levels measured in serum and liver tissue were lower in the I/R group. However, the use of GL prevented these decreases due to I/R damage. Prior administration of GL considerably alleviated histopathologic changes due to I/R injury in the intestinal and liver tissue samples. Conclusions: Our experimental study showed that I/R injury led to significant oxidative stress by inducing free oxygen radicals in intestinal and hepatic tissues. Serum and tissue MDA, SOD, and GSH-Px levels were considerably useful laboratory parameters in identifying oxidative stress. The protective effects of GL on intestinal I/R injury were promising considering these parameters.

Celecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice

It's crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after intraperitoneal therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathological evaluation and Immunohistochemical examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.

Comparative study on hepatoprotective activity of Pongamia pinnata (PP) &amp; Annona squamosa (AS) leaf extracts against anti-tubercular drugs (isoniazid &amp; rifampin) induced hepatotoxicity in rats

Objectives: - The goal of this study is to compare the effects of Pongamia Pinnata and Annona Squamosa on anti-tubercular medicines-induced hepatotoxicity in rats. Materials and Procedures: - In rats, hepatotoxicity was caused by administering a suspension of isoniazid and rifampin orally for 21 days. Pongamia Pinnata and Annona Squamosa, as well as anti-tubercular medicines, were given to the treatment groups. Biochemical &amp; histological criteria were used to measure liver destruction. Results: - The use of Pongamia Pinnata and Annona Squamosa in combination with anti-tubercular medicines dramatically reduced Serum Glutamate Pyruvic Transaminase (SGPT), Serum Glutamate Oxaloacetic Transaminase (SGOT)&amp; tissue malondialdehyde (MDA) levels. Inflammation, degeneration, and necrotic alterations in hepatocytes were reduced. Pongamia Pinnata also reduced a drop in blood Superoxide Dismutase (SOD) when compared to a control group getting only anti-tubercular medicines. Pongamia Pinnata, on the other hand, had no statistically significant effects when compared to Annona Squamosa and silymarin. Conclusion: - Annona Squamosa was found to be an effective hepatoprotective agent in rats, as it considerably reduced the hepatotoxic damage caused by anti-tubercular medicines. However, when the effects of Pongamia Pinnata &amp; Annona Squamosa or silymarin were compared, there was no statistically significant difference.

Combination Therapy of Alpha-Lipoic Acid, Gliclazide and Ramipril Protects Against Development of Diabetic Cardiomyopathy via Inhibition of TGF-β/Smad Pathway.

Background: Diabetic cardiomyopathy (DCM) is a major long-term complication of diabetes mellitus, accounting for over 20% of annual mortality rate of diabetic patients globally. Although several existing anti-diabetic drugs have improved glycemic status in diabetic patients, prevalence of DCM is still high. This study investigates cardiac effect of alpha-lipoic acid (ALA) supplementation of anti-diabetic therapy in experimental DCM. Methods: Following 12 h of overnight fasting, 44 male Sprague Dawley rats were randomly assigned to two groups of healthy control (n = 7) and diabetic (n = 37) groups, and fasting blood glucose was measured. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal (i.p.) administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). After confirmation of T2DM on day 3, diabetic rats received monotherapies with ALA (60 mg/kg; n = 7), gliclazide (15 mg/kg; n = 7), ramipril (10 mg/kg; n = 7) or combination of the three drugs (n = 7) for 6 weeks while untreated diabetic rats received distilled water and were used as diabetic control (n = 9). Rats were then sacrificed, and blood, pancreas and heart tissues were harvested for analyses using standard methods. Results: T2DM induction caused pancreatic islet destruction, hyperglycemia, weight loss, high relative heart weight, and development of DCM, which was characterized by myocardial degeneration and vacuolation, cardiac fibrosis, elevated cardiac damage markers (plasma and cardiac creatine kinase-myocardial band, brain natriuretic peptide and cardiac troponin I). Triple combination therapy of ALA, gliclazide and ramipril preserved islet structure, maintained body weight and blood glucose level, and prevented DCM development compared to diabetic control (p < 0.001). In addition, the combination therapy markedly reduced plasma levels of inflammatory markers (IL-1β, IL-6 and TNF-α), plasma and cardiac tissue malondialdehyde, triglycerides and total cholesterol while significantly increasing cardiac glutathione and superoxide dismutase activity and high-density lipoprotein-cholesterol compared to diabetic control (p < 0.001). Mechanistically, induction of T2DM upregulated cardiac expression of TGF-β1, phosphorylated Smad2 and Smad3 proteins, which were downregulated following triple combination therapy (p < 0.001). Conclusion: Triple combination therapy of ALA, gliclazide and ramipril prevented DCM development by inhibiting TGF-β1/Smad pathway. Our findings can be extrapolated to the human heart, which would provide effective additional pharmacological therapy against DCM in T2DM patients.