Activities Of Marker Enzymes Research Articles

Mitigatory antioxidant effect of Lycopene against the polystyrene microplastics-induced neurotoxicity via modulation of mTOR/Beclin-1 activities in adult male Wistar rats

BackgroundPolystyrene microplastics (PS-MPs) pose a significant threat to aquatic ecosystems, causing neuronal toxicity in aquatic species, and Lycopene (LYC), a neuroprotective substance, could potentially mitigate this issue. ObjectivesThis study examined the neurotherapeutic benefit of lycopene on the neurochemical status of rats affected by PS-MPs. MethodsTwenty Wistar rats were divided into four groups of five rats each: a vehicle group, a PS-MPs treatment group, a PS-MPs + LYC co-treatment group, and an LYC supplementation group. The experiment lasted 56 days, and all substances were administered orally. Neuronal toxicity was evaluated using oxidative stress/neurochemical biomarkers. Lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured as indicators of oxidative stress. Nitric Oxide (NO), gamma-aminobutyric acid (GABA), hydroxyl radical (●OH), ammonia, and glutamate levels were assessed to evaluate neurotransmitter balance. Cathepsin marker enzyme activity was also measured to assess lysosomal function. ResultsPS-MPs-treated animals showed increased LPO, NO, ●OH, Bcl-2 interacting protein 1 (BECLIN1), ammonia, glutamate, and reduced GABA, Mammalian targets of rapamycin (mTOR), and antioxidant activity in their cerebral cortex. The combination of PS-MPs and Lycopene treatment improved GABA, cathepsin marker enzyme activity, and brain structure, restoring normal neuronal bodies, oval nuclei, and cerebral cortex. Lycopene ameliorated oxidative stress deficits, decreased LPO, NO, ●OH, ammonia, and glutamate levels, and restored antioxidant enzyme activity. ConclusionIn conclusion, the findings suggest a potential link between PS-MPs and cognitive dysfunction through neurochemical alterations, while the administration of lycopene mitigated the neurochemical changes brought on by PS-MPs.

Assessment of Antioxidant and Hepatoprotective Effects of Kappaphycus alvarezii (Doty) Doty ex Silva Against Carbon Tetrachloride-Induced Liver Injury in Rats

Kappaphycus alvarezii (Doty) Doty ex Silva, commonly known as red algae, holds economic significance as a primary source of κ-carrageenan, which exhibits promising medicinal and therapeutic properties. This study aims to assess the antioxidant potential as well as hepatoprotective activity of the ethanolic extract of K. alvarezii (EEKA). The assays utilised to determine the antioxidant properties of EEKA were total phenolic content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. In addition, the ability of EEKA to ameliorate experimentally induced liver injury in Sprague-Dawley rats caused by carbon tetrachloride (CCl4) was evaluated. The biochemical assays involved measuring liver marker enzymes (AST and ALT) in serum as well as determining the levels of reduced glutathione (GSH), lipid peroxidation (LPO) via malondialdehyde, catalase (CAT), and glutathione S-transferase (GST) in liver homogenates. The TPC and DPPH radical scavenging activity of EEKA demonstrated relatively low antioxidant properties compared to standard references. However, CCl4-induced groups exhibited significantly increased levels of AST and ALT, along with depletion of antioxidant status (GSH, CAT, and GST) indicated by LPO. Pretreatment with EEKA resulted in slightly decreased liver marker enzyme activity and LPO, coupled with an increase in antioxidant status. These findings suggest that EEKA contains active principles capable of counteracting the hepatotoxic effects induced by CCl4.

HEPATOPROTECTIVE EFFECT OF GOLDEN VOLODUSHKA (BUPLEURUM AUREUM L.) HERB EXTRACT OF DRY IN EXPERIMENTAL TOXIC HEPATITIS IN RATS

Introduction. The search for new medicines, including those of plant origin, for the treatment of diseases of the hepatobiliary system is relevant and timely. A promising source for the development of hepatoprotective drugs is golden volodushka (Bupleurum aureum L.). To date, a large evidence base has been accumulated for the biochemical study of this plant, its pharmacological activity has been scien-tifically proven. Good stocks of golden volodushka in the wild, the simplicity of its harvesting and the possibility of cultivation were noted. The VILAR State Medical University has developed a method for obtaining volodushka golden herb extract of dry. Aim. The study of the pharmacotherapeutic efficacy of volodushka golden (Bupleurum aureum L.) herb extract of dry in case of liver damage under experimental conditions. Material and methods. In the studies, white non-linear male rats with a body weight of 180-200 g were used. Volodushka extract was studied at doses of 50 and 100 mg/kg. The comparison drug was silimar at a dose of 100 mg/kg. Experimental CCl4 – induced hepatitis in rats was caused by a single subcutaneous injection of 50% carbon tetrachloride oil solution one hour after the last administration of the studied extract and the comparison drug. After 48 hours, blood was taken from the tail vein of rats, serum was obtained and its biochemical analysis was carried out. Next, the rats eu-thanized in a CO2 chamber and the liver extracted for pathophysiological evaluation. Tetracycline hepatitis was caused by intragastric administration of tetracycline to animals at a dose of 500 mg/kg. Then, after 48 hours, blood was taken from the animals, serum was obtained and its biochemical analysis was carried out. Results. Volodushka golden grass dry extract on a model of carbon tetrachloride hepatitis exhibits a hepatoprotective effect, which is confirmed by a comparative pathophysiological study and a study of the activity of enzyme markers of the morphofunctional state of the liver in rat blood serum. In the tetracycline hepatitis model, the studied extract also has a hepatoprotective effect, which is confirmed by biochemical studies. Conclusions. Studies of volodushka extract in conditions of experimental liver lesions have shown that the studied extract in experimental therapeutic doses has a pronounced hepatoprotective effect and is promising for the creation of a herbal medicine for the prevention and treatment of diseases of the digestive system.

Exploring the cytoprotective potential of flavonoid fraction from Carica papaya L. Cultivar ‘Red Lady' Leaf: Insights into Nrf2 activation via in-vitro and in-silico approaches

Flavonoids play a significant role in mitigating the production of reactive oxygen species (ROS) and subsequent oxidative stress. In the present study we aimed to evaluate the cytoprotective and antioxidant defense mechanism of flavonoid fraction from Carica papaya L. (FFCP) leaf in human PBMC. For this investigation, the human PBMCs were lotted into three groups viz., negative control, positive control (treated with H2O2), and experiment group (pretreated with FFCP and challenged with H2O2). The cytoprotective mechanism was evaluated by assessing the intracellular ROS and Ca2+ mobilization, membrane and DNA damages, antioxidant enzymes, and Nrf2 activation. In-silico analysis was employed for assessing the interactions of flavonoids in FFCP with the Nrf2 binding pocket of Keap 1 protein. The results of the experiment unveiled that FFCP protected the human PBMCs from H2O2 induced oxidative damages such as lipid peroxidation, LDH leakage, DNA breakage, reduced the intracellular ROS and Ca2+ mobilization as compared to positive control. FFCP pretreatment effectively improved the activity of key antioxidant enzyme markers, such as SOD (1.66 ± 0.032-fold increase), CAT (2.24 ± 0.09-fold increase), GPx (1.94 ± 0.05-fold increase), and GR (1.81 ± 0.14-fold increase). Furthermore, the FFCP modulated the Nrf2 gene expression (a 2.38 ± 0.25 -fold) and its translocation into the nucleus as compared to the positive control. In-silico analysis enunciated that all flavonoids exhibited strong affinity with the Nrf2 binding pocket of Keap1 protein via stable hydrogen bonding and hydrophobic interactions. These observations suggest that FFCP is a natural source of bioactive compounds with nutraceutical benefits for combating oxidative stress-associated diseases by protecting the cells from oxidative stress induced damages as well as by instigating antioxidant defense mechanisms.

Alcohol promotes liver fibrosis in high fat diet induced diabetic rats.

Type 2 diabetes (T2DM) and alcoholism are considered to be lifestyle-associated independent risk factors in fatty liver diseases (FLD) mediated cirrhosis and hepatocellular carcinoma (HCC). A combined effect of both these conditions may exacerbate the pathological changes and a pre-clinical exploration of this is expected to provide a mechanical detail of the pathophysiology. The present study aims to understand the effect of alcohol on pre- diabetic and type 2 diabetic female Wistar rats. In this experimental study, 12 Wistar rats (180-220 g) were randomly assigned into three groups: Normal (fed normal rat chow), alcohol (20 %) fed diabetic (HFD+STZ), and pre-diabetic rats (HFD alone). After, two months of the experimental period, blood and liver tissues were collected lipid metabolic alteration, liver injury, and fibrosis were determined following biochemical and histological methods. Data were analyzed using one-way ANOVA and Dunnett's Post Hoc test. Significant dyslipidemia was observed in the liver tissues of diabetic and pre-diabetic rats following alcohol ingestion. A significant (p<0.05) increase in lipid peroxidation status, and hepatic marker enzyme activities (p<0.0001) were observed in diabetic animals. In corroborating with these observations, hematoxylin and eosin staining of hepatic tissue revealed the presence of sinusoidal dilation along with heavily damaged hepatocytes and inflammatory cell infiltration. Further, significantly (p<0.001) increased hepatic hydroxyproline content and extended picrosirius red stained areas of collagen in liver tissue indicated initiation of fibrosis in alcohol-fed diabetic rats. Overall, the results indicate that alcohol consumption in T2DM conditions is more deleterious than pre diabetic conditions in progressing to hepatic fibrosis.

The effects of iron oxide nanoparticles on antioxidant capacity and response to oxidative stress in Mozambique tilapia (Oreochromis mossambicus, Peters 1852).

Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs), as they have been reported to induce oxidative stress and inflammatory responses, whilst prolonged exposure to high IONP concentrations may lead to cyto-/genotoxicity. Besides, there is concern about its environmental impact. The aim of our study was to investigate the effects of IONPs on the antioxidant defence system in freshwater fish Mozambique tilapia (Oreochromis mossambicus, Peters 1852). The fish were exposed to IONP concentration of 15 mg/L over 1, 3, 4, 15, 30, and 60 days and the findings compared to a control, unexposed group. In addition, we followed up the fish for 60 days after exposure had stopped to estimate the stability of oxidative stress induced by IONPs. Exposure affected the activity of antioxidant and marker enzymes and increased the levels of hydrogen peroxide and lipid peroxidation in the gill, liver, and brain tissues of the fish. Even after 60 days of depuration, adverse effects remained, indicating long-term nanotoxicity. Moreover, IONPs accumulated in the gill, liver, and brain tissues. Our findings underscore the potential health risks posed to non-target organisms in the environment, and it is imperative to establish appropriate guidelines for safe handling and disposal of IONPs to protect the aquatic environment.

INVESTIGATION OF THE EFFICIENCY OF NON-STEROIDAL ANTI-INFLAMMATORY VETERINARY MEDICINAL PRODUCT IN THE COMPLEX TREATMENT OF DISEASES OF THE MUSCULOSKELETAL SYSTEM OF PIGS

The article presents the results of clinical trials of a non-steroidal anti-inflammatory veterinary drug when administered to fattening piglets with clinical signs of musculoskeletal diseases. For the treatment of the diseases, piglets of the experimental (I) and control (II) groups received an antimicrobial drug based on the tetracycline antibiotic. The animals of the experimental group were additionally administered orally with drinking water the test non-steroidal anti-inflammatory drug based on acetylsalicylic, ascorbic and citric acids, in the recommended dosage by the manufacturer. Blood for laboratory tests was selected from piglets before and after the use of drugs. Studies of hematological and biochemical parameters were conducted according to generally accepted methods. The therapeutic efficiecy of the drug and its effect on the morphofunctional state of the body was evaluated by comparing the statistically processed data obtained before and after treatment, as well as in comparison with the indicators of animals of the control group. The analysis of hematological parameters of piglets during the experiment showed a decrease in the number of leukocytes in the animal’s blood after the use of drugs. The normalization of the leukogram was also noted by reducing the relative number of rod-nuclear neutrophils. In particular, this indicator decreased by 17.4% in group I piglets, and by 12% in group II piglets. It is noted that the clinical response to therapy was faster and more pronounced in animals, which used a non-steroidal anti-inflammatory drug in combination with an antimicrobial drug than in piglets, which were treated only by antibiotic. According to the results of biochemical studies, it was found that the content of urea in the serum of animals of both groups before the use of drugs exceeded more than 3 times the upper limit of physiological values for a given age group of piglets. After therapy with the drugs a significant decrease in the urea content in the blood serum of groups 1 and 2 animals was noted by 3.42 and 2.98 times, respectively. It is established that the activity of marker enzymes of the liver physiological state (ALT, AST) in the serum of group I piglets after complex treatment with the studied drugs was slightly reduced and was within the physiological values. In the serum of group II animals, which were treated only with antimicrobial drug, ALT activity increased by 12,0 %, and AST – by 38,6 %, compared to the initial data, and exceeded the limit of physiological values. An increase in the content of iron by 37.4 % in the blood of group I piglets, compared to the period before drug administration, was noted. No adverse reactions and negative phenomena were detected during the use of the test drug, and the drug was well tolerated. According to the clinical condition of the experimental group animals and the results of laboratory tests it was established that the use of non-steroidal anti-inflammatory drugs based on acetylsalicylic, ascorbic and citric acids simultaneously with antimicrobial therapy led to a faster improvement in the state of the musculoskeletal system. Observation during the month of the piglet’s clinical conditions confirmed the safety of the drug in the recommended dosage and method of administration in the combined treatment of inflammatory processes of the musculoskeletal system.

Effects of oral exposure to iron oxide nanoparticles on reproductive system of male rats

To investigate the effects of oral exposure to iron oxide nanoparticles(Fe_2O_3NPs) on the reproductive system of male rats. Forty male SD rats were randomly divided into control group and low, medium, high dose groups, 10 rats in each group, normal saline and 50, 100 and 200 mg/kg Fe_2O_3NPs suspension were given by gavage, respectively. The volume of gavage was 10 mL/kg for 28 days. The body weight was weighed every three days, and the body weight changes of rats were recorded. After intraperitoneal anesthesia with 10% chloral hydrate, the rats were sacrificed by cervical dislocation, and the testis and epididymis were collected. Weigh and calculate the testicular coefficient and epididymal coefficient, the pathological sections of rat testis were observed by hematoxylin-eosin staining, the number of epididymal sperm was counted under an optical microscope and the sperm deformity rate was calculated. The activities of acid phosphatase(ACP), alkaline phosphatase(AKP), lactate dehydrogenase(LDH) and γ-glutamyl transpeptidase(γ-GT), the activity of superoxide dismutase(SOD), and the contents of glutathione(GSH) and malondialdehyde(MDA) in rat testis homogenate were detected by kit method. Compared with control group, there was no significant difference in body weight, testicular coefficient and epididymal coefficient in each dose group. In the medium and high dose groups, the arrangement of spermatogenic epithelium was disordered and spermatogenic cells decreased. The number of sperm in high dose group was decreased, and the sperm deformity rate in medium and high dose groups was increased(P&lt;0.01). The activity of ACP in medium and high dose groups increased(P&lt;0.05), and the activity of γ-GT decreased(P&lt;0.01). There was no significant change in the activity of AKP and LDH in testicular homogenate of rats in each group(P&gt;0.05). The level of GSH in medium dose group was increased(P&lt;0.05), and the content of MDA in medium and high dose groups was increased(P&lt;0.01). There was no significant difference in SOD activity among the groups(P&gt;0.05). Under the conditions of this experiment, Fe_2O_3NPs can cause damage to the structure of rat testicular tissue, reduce the number of sperm, increase the rate of sperm deformity, interfere with the activity of marker enzymes in testicular tissue and induce oxidative stress injury, which has a negative impact on the reproductive system of male rats.

ИЗУЧЕНИЕ ГЕПАТОТОКСИЧЕСКОГО ВОЗДЕЙСТВИЯ ГИДРОКСИДА АЛЮМИНИЯ, ВВОДИМОГО В ЖЕЛУДОЧНО-КИШЕЧНЫЙ ТРАКТ КРЫС, В ПОДОСТРОМ ЭКСПЕРИМЕНТЕ

Aluminum (Al) has various toxic effects on biosystems. Essential properties of aluminum have not been established, the mechanisms of impairment are insufficiently studied. The negative impact of aluminum on the human body leads to liver damage, increased oxidative stress and development of hepatotoxicity. Blood enzymes are characteristic markers of liver function and are used to assess the toxicity of environmental pollutants. The aim of the study was to investigate the activity of enzyme markers of hepatotoxicity, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) in the blood of laboratory animals after subacute intoxication with aluminum hydroxide (Al(OH)3). The experiment was conducted on 80 white rats divided into 4 groups. Three groups of animals orally received Al(OH)3 solution of different concentrations for a month, the control group was administered distilled water. At the end of the experiment, enzyme activity in the blood serum was measured. The increase in the AST level in the first group is associated with changes in hepatocytes. The decrease in ALT activity in the experimental groups is associated with the peculiarities of aluminum excretion. By analogy with AST, an increase in the concentration of LDH was registered in the first group, while a decrease in the level of the indicator was shown in the second and third groups. A decrease in the activity of alkaline phosphatase indicates a violation of metabolic processes in cells. The effect of Al(OH)3 for a month caused certain changes in liver markers in the blood serum of experimental animals. For a more complete understanding of the hepatotoxic effects of aluminum, additional biochemical studies are needed to assess the activity of antioxidant defense enzymes.

Hepatoprotective efficacy of Lagenaria siceraria seeds oil against experimentally carbon tetrachloride-induced toxicity.

The liver is crucial for maintaining normal metabolism in the body. Various substances, such as toxic chemicals, drugs, and alcohol, can damage hepatocyte cells, leading to metabolic imbalances. The experiment aimed to determine the efficacy of Lagenaria siceraria seed oil (LSS) as a hepatoprotective agent against acute hepatotoxicity triggered by carbon tetrachloride (CCl4). A total of 20 rats were randomly separated into four groups. The control group: rats received 2 ml of distilled water orally, followed by 1.25 ml of olive oil intraperitoneally (i.p.) after 30 minutes. CCL4 group: rats were given a single intraperitoneal dose of 1.25 ml/kg b.w. of CCl4 in a 1:1 mixture with olive oil. Silymarin group: received 100 mg of silymarin per kg of b.w. diluted in 2 ml of distilled water orally, followed by CCl4 treatment after 30 minutes. LSS oil group: received LSS oil at 3g/kg b.w. orally, followed by CCl4 treatment after 30 minutes. Blood samples were collected to assess liver enzymes (AST, ALT, and ALP), proteins and bilirubin fractions, and redox status (catalase, reduced glutathione (GSH), and malondialdehyde (MDA)) were assessed in hepatic tissues. Changes in liver histopathological examination were also evaluated. In CCl4-treated rats, there was a significant increase in serum liver marker enzyme activity (ALP, AST, and ALT) along with a significant elevation (p < 0.05) in total bilirubin, indirect bilirubin, and direct bilirubin compared to the control rats. However, all these parameters decreased in the CCl4+ Silymarin and CCl4+LSS groups compared to CCl4-treated rats. There was a significant decline in total protein level and serum albumin in all experimental groups compared to the control, while globulin levels significantly increased in all experimental groups. There was a significant (p < 0.05) reduction in the level of GSH and catalase, with an increase in MDA level in CCl4 rats compared to other rats. Histopathological investigation of the LSS-treated group showed a hepatoprotective effect against CCl4. The study revealed that LSS oil has antioxidant activity against CCl4-induced toxicity.

Study of the Effect of Cadmium Chloride on Some Marker Liver Enzymes of Experimental Animals

Introduction. Cadmium (Cd) is one of the most powerful and dangerous pollutants. Cd exposure is associated with multiple organ damage in both animals and humans. The mechanism of Cd toxicity is the disruption of the body’s antioxidant system (AOS), which leads to transformation of the functional integrity of the liver. The extent of target organ damage can be examined by measuring concentrations of key indicators of hepatocellular injury. The purpose of the work is to evaluate changes in the activity of enzyme markers of hepatotoxicity in the blood serum of laboratory animals after oral exposure to an aqueous solution of cadmium chloride (CdCl2) under the conditions of a subchronic experimental model with a period of remission. Materials and methods. The study was conducted on 40 white outbred rats. Animals of three experimental groups were intragastrically administered a pollutant in various dosages for 3 months. The duration of the remission stage was 1 month. The activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) was determined in the blood serum of animals. Results. When CdCl2 was administered to animals at a dose of 1 μg/kg, an increase in AST activity was observed by 45.9% relative to the control (p=0.006). An increase in the concentration of ALT and LDH is shown. A dose-dependent decrease in the level of alkaline phosphatase was revealed in three groups of animals by 24.7%, 37.5% and 55.4%, respectively (p=0.002). The noted trends indicate pathological processes occurring in hepatocytes. Conclusion. In the course of this study, it was found that under the conditions of a subchronic model of the experiment with a period of remission, cadmium, having a pronounced hepatoxic effect, induces liver damage in experimental animals.

REAP+: A single preparation for rapid isolation of nuclei, cytoplasm, and mitochondria

REAP+ is an enhanced version of the rapid, efficient, and practical (REAP) method designed for the isolation of nuclear fractions. This improved version, REAP+, enables fast and effective extraction of mitochondria, cytoplasm, and nuclei. The mechanical cell disruption process has been optimized to cerebral tissues, snap-frozen liver, and HT22 cells with remarkable fraction enrichment. REAP+ is well-suited for samples containing minimal protein quantities, such as mouse hippocampal slices. The method was validated by Western blot and marker enzyme activities, such as LDH and G6PDH for the cytoplasmic fraction and succinate dehydrogenase and cytochrome c oxidase for the mitochondrial fraction. One of the outstanding features of this method is its rapid execution, yielding fractions within 15 min, allowing for simultaneous preparation of multiple samples. In essence, REAP+ emerges as a swift, efficient, and practical technique for the concurrent isolation of nuclei, cytoplasm, and mitochondria from various cell types and tissues. The method would be suitable to study the multicompartment translocation of proteins, such as metabolic enzymes and transcription factors migrating from cytosol to the mitochondria and nuclei. Moreover, its compatibility with small samples, such as hippocampal slices, and its potential applicability to human biopsies, highlights the potential application in medical research.

1-Deoxynojirimycin Mitigates Glycogen and Carbohydrate Metabolic Enzyme Alterations in High Glucose-Induced Diabetic Tilapia: Implications for Therapeutic Intervention

This study investigated the effects of 1- deoxynojirimycin (DNJ) on blood glucose levels, body weight changes, glycogen levels, and carbohydrate marker enzyme activity in a high glucose-induced experimental diabetic tilapia model. We utilized spectrophotometry assay methods to achieve this objective. DNJ treatment significantly reduced blood glucose and mitigated body weight loss compared to the diabetic control group. Furthermore, DNJ treatment increased glycogen levels in liver and muscle tissues, suggesting its potential to enhance glycogen synthesis or reduce glycogen breakdown. DNJ treatment also modulated the activity of carbohydrate marker enzymes, indicating its possible inhibitory effect on enzymes involved in carbohydrate absorption and breakdown, which in turn may improve glucose homeostasis and control. The results of this study highlight DNJ's potential as a therapeutic agent for diseases associated with glycogen metabolism and glucose homeostasis, as well as its ability to influence body weight changes in diabetic conditions. Our findings contribute to the growing body of research on DNJ as a potential therapeutic agent for illnesses linked to glycogen and underscore its therapeutic potential for future treatments targeting glucose metabolism, glycemic control, and weight management.

Hepatoprotective effect of D-Limonene Against Adriamycin Induced Hepatotoxicity in Experimental Rats

The presence study is to evaluate hepatoprotective function of d-limonene against adraimycin induced hepatotoxicity. Monoterpenes plays an essential role to fight against various diseases. Among the various monoterpenes an efficient d-Limonene plays a fundamental role to fight against hepatotoxicity caused by cancer chemotheraphy treatment. Male albino Wistar rats were administrated with ADR (15mg/Kg body weight) in six equal injections and the protection efficacy of d-limonene (100mg/Kg body weight) was examined with reference to tissue AST level and the pathological studies was examined by microscopic study. Rats treated with ADR results in elevated level of liver AST marker enzymes, whereas the level of AST was controlled when administrated with d-Limonene. However Histopathological proof added more protective role of rats treated with d-limonene against hepatotoxicity. ADR administration of 15mg/Kg body weight of rats increase the level of hepatotoxicity by increasing the marker enzyme activity and show severe morphological changes. The final outcome from our result suggests that d-limonene (100mg/Kg body weight) a vibrant monoterpene act as latent hepatoprotective negotiator by attenuating ADR induced hepatotoxicity.

Lactobacillus plantarum Enhanced the Cardioprotective Efficacy of Arctiin in Isoproterenol Cardiac Injury in BALB/c Mice

Background Isoproterenol is a drug used for the treatment of bradycardia that has many side effects due to its non-selective β-adrenoceptor agonist properties. Aim In this study, we evaluated an in vivo experimental model for isoproterenol (ISO) cardiac injury using BALB/c mice and protective treatment with a combined optimized dose of Arctiin (AR) and Lactobacillus plantarum (LP) (ARLP; 30 mg/kg b.w. AR and viable 106 CFU/mL LP p.o.) together. Introduction Isoproterenol causes cardiac injury in many instances. Arctiin is a naturally occurring lignin glycoside present in many herbal medicinal plants that has many beneficial effects for humans. Lactobacillus plantarum is yet another beneficial probiotic that benefits largely to humans. Materials and Methods Male BALB/c mice in appropriate groups (6 animals each) were treated with ARLP for 7 days with ISO administration (100 mg/kg i.p.) on days 5 and 6. On the 8th day, animals were sacrificed. Serum and heart samples were collected for further processing. CK-MB, cardiac troponin, AST, ALT, LDH, GST, GPx, CAT, SOD, GSH, GSSG, MDA, nuclear factor kappa B (NFκB), TNF-α, and IL-6 by ELISA and gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) were estimated in samples. Results Mice administered with ISO showed a prominent rise in the serum marker enzyme activities and tissue oxidative stress markers (MDA and GSSG). Furthermore, marked reductions in body weight and enzymatic and non-enzymatic antioxidant levels were noticed in ISO toxicity. Alterations in proinflammatory cytokines (TNF-α and IL-6) and Nrf2 levels by RT-PCR were analyzed. Histopathology of the heart also indicated cardiac injury in ISO-intoxicated mice. ARLP pretreatment prevented all these cardiac injuries and exerted significant ( p ≤ 0.05) prophylactic protection toward cardiac tissue. Further, we analyzed the possible interactions between AR and LP in vitro, to understand the influence of ARonLP, which showed no significant suppressive/antibacterial activity on LP. Conclusion In conclusion, ARLP exerts a strong cardioprotective and anti-inflammatory activity in cardiovascular injury.

Antioxidant, anti-inflammatory, and anti-apoptotic effects of genkwanin against aflatoxin B1-induced testicular toxicity

Aflatoxin B1 (AFB1) is the most hazardous aflatoxin that causes significant damage to the male reproductive system. Genkwanin (GNK) is a bioactive flavonoid that shows antioxidant and anti-inflammatory potential. Therefore, the current study was planned to evaluate the effects of GNK against AFB1-induced testicular toxicity. Forty-eight male rats were distributed into four groups (n = 12 rats). AFB1 (50 μg/kg) and GNK (20 mg/kg) were administered to the rats for eight weeks. Results of the current study revealed that AFB1 exposure induced adverse effects on the Nrf2/Keap1 pathway and reduced the expressions and activities of antioxidant enzymes. Additionally, it increased the levels of oxidative stress markers. Furthermore, expressions of steroidogenic enzymes were down-regulated by AFB1 intoxication. Besides, AFB1 exposure reduced the levels of gonadotropins and plasma testosterone, which subsequently reduced the epididymal sperm count, motility, and hypo-osmotic swelled (HOS) sperms, while increasing the number of dead sperms and causing morphological anomalies of the head, midpiece, and tail of the sperms. In addition, AFB1 decreased the activities of testicular function marker enzymes and the levels of inflammatory markers. Moreover, it severely affected the apoptotic profile by up-regulating the expressions of Bax and Casp3, while down-regulating the Bcl2 expression. Besides, AFB1 significantly damaged the histoarchitecture of testicular tissues. However, GNK treatment reversed all the AFB1-induced damages in the rats. Taken together, the current study reports the potential use of GNK as a therapeutic agent to prevent AFB1-induced testicular toxicity due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Punicalagin attenuates myocardial oxidative damage, inflammation, and apoptosis in isoproterenol-induced myocardial infarction in rats: Biochemical, immunohistochemical, and in silico molecular docking studies

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Punicalagin (PU), the major ellagitannin found in pomegranates, is characterized by multiple antioxidant activities. The aim of this study is to assess the protective effects of PU against isoproterenol (ISO)-induced acute myocardial damage and to investigate its underlying vascular mechanisms using rat model. MethodsRats were randomly divided into five groups and were treated orally (p.o.) with PU (25 and 50 mg/kg) for 14 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 15th and 16th days to induce Myocardial infarction. Cardiac markers, oxidative stress markers, and inflammatory cytokines levels were determined in the heart tissue. Immunohistochemistry analysis was performed to determine the protein expression pathways of inflammation, apoptosis and oxidative stress (Nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) in all the groups. In silico study was carried out to evaluate the molecular interaction of PU with some molecular targets. ResultsOur results showed that ISO-induced cardiac tissue injury was evidenced by increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH), associated with several histopathological changes. ISO also induced an increase of MDA, PCO, NO, and 8-hydroxy-2-deoxyguanosine (8-OHdG), along with a decrease of antioxidant enzyme activities in the myocardial tissues. In addition, an increase of TNF-α, NF-κB, IL-6, IL-1β, iNOS, Nrf2 and (HO-1) was observed. Pre-treatment with PU reduced myocardial infract area, ameliorated histopathological alterations in myocardium, and decreased activities of myocardial injury marker enzymes in ISO-induced rats. In addition, PU remarkably restored ISO-induced elevation of lipid peroxidation and decrease of antioxidants, significantly reduced myocardial pro-inflammatory cytokines concentrations in this animal model. Molecular docking analysis of PU with protein targets showed potent interactions with negative binding energies.In conclusion, PU can protect the myocardium from oxidative injury, inflammatory response, and cell death induced by ISO by upregulating Nrf2/HO-1 signaling and antioxidants.

Aseptic inflammation as the essential link in the pathogenesis of endometrioid disease

The paper was aimed at deter­mination of the quantitative activity of iNOS and Arg1, as well as M1 and M2 phenotype macrophages in women with endometrioid disease to establish their role in the pathogenesis of endometriosis. A prospective study was performed in gynecological units of the medical facilities of Poltava city. 140 women of reproductive age who made up the main group (110 women with endometrioid disease) and the control group (30 women without endometrioid disease) voluntarily participated in the study. All women underwent planned surgical treatment for existing gynecological pathology. Before surgical treatment, women were examined in accordance with the current Orders of the Ministry of Health of Ukraine. The spectrophotometric method was used to determine the enzymatic markers of macrophages (in the endometrium and peritoneal fluid) polarized into M1(iNOS) and M2 (Arg1) phenotypes. The type of macrophages was determined individually in each patient according to the ratios: in iNOS&gt;Arg1, the M1 macrophage type prevailed; in Arg1&gt;iNOS, the M2 macrophage type prevailed. When examining endometrial samplings in women from the main group, the iNOS indicator was by 1.4 times higher compared to women from the control group. The obtained results at the stage of entry into the abdominal cavity showed that mostly women from the main group suffered from the pelvic adhesion, especially stage 3 and stage 4. Among the obtained results, the increased quantitative activity in the peritoneal fluid of both iNOS and Arg1 in women of the main group was significant compared to the control group. When comparing the stages of endometrioid disease to the rates of quantitative activity of macrophage enzyme markers (in peritoneal fluid), it was found that the increase in the stage of the disease (from stage 3 to stage 4) caused an increase in the quantitative activity of Arg1 by 1.9 times and a decrease in the quantitative activity of iNOS by 2.9 times. Therefore, the planning of surgical intervention for women with endometrioid disease should consider a significant percentage of the pelvic adhesive disease, especially at the severe stages. Initiation of the chronic aseptic inflammatory process in endometrioid disease is caused by an increased quantitative activity of iNOS in the endometrium. In the pathogenesis of endometrioid disease, the presence of M2 phenotype macrophages in the peritoneal fluid is important, while the switching of macrophage phenotypes from a pro-inflammatory subpopulation to an anti-inflammatory one is crucial.

Curculigo pilosa rhizome Supplementation Reverses P-Hydroxyacetanilide-Induced Oxidative Stress and Lipid Profile Dysfunction in Rats

Exposure to drug toxicity results in stress and dysfunction of metabolizing enzymes that cause illnesses and diseases. Consumption of medicinal plant rhizomes is a regime for managing the complications. On the activities of some oxidative stress marker enzymes (catalase, glutathione, and superoxide dismutase), as well as the concentration of lipid profiles (cholesterol, triglycerides, and phospholipids) of p-hydroxyacetanilide (pPHA)-induced toxicity in rats, the effects of an aqueous extract of Curculigo pilosa (C. pilosa) rhizome were assessed. Forty rats were randomly grouped into eight groups (n = 5). The control group; aqueous extract of C. pilosa rhizome group; 750 mg/kg and 1000 mg/kg per body weight of pPHA group; the preventive groups (aqueous extract of C. pilosa rhizome and 750 mg/kg per body weight of pPHA; aqueous extract of C. pilosa rhizomes and 1000 mg/kg per body weight of pPHA); and the curative groups (750 mg/kg per body weight of pPHA and aqueous extract of C. pilosa rhizome; 1000 mg/kg body weight of pPHA and aqueous extract of C. pilosa rhizome). The oxidative stress marker enzymes and lipid profiles were analyzed spectrophotometrically in the serum, kidney, brain, and liver of the animals on the seventh and fourteenth days after the administrations. The results show that pPHA decreases the oxidative stress marker activities and the lipid profile concentrations in all the compartments, but the pre- and post-treatment with an aqueous extract of C. pilosa rhizome improved the activities of the stress marker enzymes and the lipid profiles dysfunction. The result suggests that an aqueous extract of C. pilosa rhizome has preventive and curative therapeutic potential for pPHA-induced toxicity.

Preventive Effect of 6-shogaol on D-galactosamine Induced Hepatotoxicity Through NF-?B/MAPK Signaling Pathway in Rats.

This analysis aims to see whether 6-shogaol could protect rats against D-galactosamine (D-GalN)-induced Hepatotoxicity. The Wistar rats were divided into four groups (n=6). Group 1 received a standard diet, Group 2 received an oral administration of 6-shogaol (20 mg/kg b.wt), Group 3 received an intraperitoneal injection of D-GalN (400 mg/kg b.wt) on 21st day, and Group 4 received an oral administration of 6-shogaol (20mg/kg b.wt) for 21 days and D-GalN (400 mg/kg b.wt) injection only on 21st day. The hepatic marker enzymes activity, lipid peroxidative markers level increased significantly and antioxidant activity/level significantly reduced in D-GalN-induced rats. 6-shogaol Pretreatment effectively improves the above changes in D-GalN-induced rats. Further, inflammatory marker expression and MAPK signaling molecules were downregulated by 6-shogaol. These findings showed that 6-shogaol exerts hepatoprotective effects via the enhanced antioxidant system and attenuated the inflammation and MAPK signaling pathway in D-GalN-induced rats.