Activities Of Marker Enzymes Research Articles

Betulin/2-hydroxypropyl-β-cyclodextrin inclusion complex: Physicochemical characterization and hepatoprotective activity

The thermodynamic and spectroscopic parameters of the betulin/2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex and its hepatoprotective activity were investigated in rats with nonalcoholic steatohepatitis (NASH). The pentacyclic triterpene betulin was isolated from birch bark and complexed with HPβCD. The parameters of inclusion complex formation were evaluated by infrared spectroscopy and differential scanning and isothermal titration calorimetries. The aqueous solubility and stability of betulin were significantly increased due to the formation of a stable inclusion complex with a stoichiometry of 1:1. The determined changes in molar enthalpy (ΔH < 0), entropy (ΔS > 0) and free energy (ΔG < 0) values indicate energetically favorable and spontaneous nature of the ligand-receptor interaction. The association constant of the betulin/HPβCD complex formation was equal to 1330 ± 111 M−1, as was determined by a calorimetric method. The complex formation was enthalpy and entropy driven. In rats with NASH induced by a high-fat diet, the oral administration of the betulin/HPβCD complex at 50 mg/kg betulin equivalent resulted in marked liver protective effects exceeding those of a higher dose (100 mg/kg) of betulin alone. Specifically, the betulin/HPβCD complex decreased lipid accumulation, the number of inflammatory foci in the liver, the activities of the serum marker enzymes, and the circulating TNFα level. Therefore, the complexation of betulin with HPβCD, improving aqueous solubility and, in turn, bioavailability, could be a prospective strategy to enhance antioxidative, anti-inflammatory, and hepatoprotective properties of betulin as a promising candidate for treatment of NASH.

Trichloroethylene injures rat liver and elevates the level of peroxisomal bifunctional enzyme (Ehhadh)

Trichloroethylene (TCE) is a common industrial solvent and an occupational toxicant. TCE exposure can cause severe hepatotoxicity, but its mode of action is poorly understood. Many studies have shown TCE-induced liver damage in mice, while few have examined the effects of TCE in rats. To explore the effects of TCE in Sprague–Dawley (SD) rats and the potential mechanisms in TCE-induced hepatocytotoxicity. The liver index and activities of liver damage marker enzymes (ALT, AST and ALP) in rat serum were elevated along with the increase in TCE dose, while the levels of total proteins and albumin in serum were reduced. The results suggest that TCE is hepatotoxic in rats. 2D-DIGE electrophoresis showed that the levels of 66 liver proteins in TCE-treated rats were abnormally altered (39 up-regulated and 27 down-regulated). In these proteins, six enzymes were related to liver damage and carcinogenesis as indicated by bioinformatics analysis, and Western blot analysis confirmed the alterations of three of them, i.e., aldehyde dehydrogenase 2 (Aldh2), glutathione S-transferase Mu 1 (Gstm1) and peroxisomal bifunctional enzyme (PBE, also named as Ehhadh). PBE was the only protein elevated in a dose dependent manner. Whether PBE can be a biomarker of TCE hepatotoxicity needs to be further studied. These findings indicate that TCE induces liver injury in rats.

Enteromorpha prolifera Extract Protects against Scopolamine‐induced Memory Impairment in Mice

Enteromorpha prolifera (EP) contains various nutrients and phytochemicals that have been reported to play role in antioxidant activity, hypolipidemic and immunomodulatory. However, the neuroprotective effect of EP has not been reported. The present study examined whether EP ethylacetate extract(EPE) improves memory impairment induced by scopolamine. EPE (50 or 100 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with EPE for another 14 days. Memory performance was evaluated using the Morris water maze test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities, biomarkers of oxidative stress and the loss of neuronal cells in hippocampus was evaluated by histological examinations. Administration of EPE significantly restored memory impairments induced by scopolamine, as demonstrated by the Morris water maze test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with EPE inhibited the AChE activity and increased the ChAT activity in the brain of memory impaired mice induced by scopolamine. Additionally, the administration of EPE significantly prevented the increase in lipid peroxidation and the decrease in GSH levels in brain of mice treated with scopolamine. Also, the EPE treatment restored the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) to control level. Furthermore, scopolamine‐induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by EPE treatment. It is suggested that EPE may be a useful for mitigating memory improvement via the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine.

Evaluation of the sub-acute toxicity of Acacia catechu Willd seed extract in a Wistar albino rat model

Acacia catechu (A. catechu) or Khair (Hindi) is used in several herbal preparations in the Ayurvedic system of medicine in India. Traditionally, this drug is beneficial against several gastrointestinal and stomach related ailments, and leprosy. The present investigation was carried out to evaluate the sub-acute oral toxicity of the ethanolic extract of A. catechu seeds in Wistar albino rats. Results obtained from the quantitative chemical analysis of A. catechu seed extract were compared with commercially available standards. A. catechu seed extract was administered orally at the doses of 250, 500 and 1000 mg/kg b.w. daily for 28 days. General behavior, bodyweight and mortality were examined during the entire study period. At the end of 28 days, hematological and biochemical parameters along with the relative organ weights were determined. It was observed that the extract did not induce death or any significant changes in the body weight, relative weight of vital organs and in hematological parameters for up to a dose of 1000 mg/kg. The oral administration of the plant extract did not produce any significant changes in the levels of glucose. In addition, there were no significant changes in the activity of both hepatotoxic and nephrotoxic marker enzymes in the serum. Oral administration of A. catechu also did not produce any significant changes in the levels of oxidative markers. Furthermore, the findings from the biochemical studies were, well corroborated with the histological findings.

Hepatic- and Renal protective Effects of Chrysophyllum albidum (African Star Apple) Fruit-Skin Supplementation on Streptozotocin-Induced Diabetic Rats

Chrysophyllum albidum commonly called African star apple, has been reported for its antidiabetic potential but its effect on liver and kidney functions in diabetic rats has not been well investigated. This study investigated effects of Chrysophyllum albidum fruit-skin (CAFS) supplemented diet on Streptozotocin-induced diabetic rats. Diabetes was induced intraperitonealy at a single dose of 50mg/kg bw of Streptozotocin (STZ). Forty male Wistar rats weighing averagely 170g were randomly divided into four groups of ten rats each; Group 1-Normal control, Group 2-Diabetic control, Group 3-Diabetic rats treated Glibenclamide, Group 4-Diabetic rats treated 70g/kg CAFS supplemented diet. After four weeks of treatment, the rats were sacrificed. Liver function biomarkers (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP)) activities, kidney function biomarkers (Creatinine and Urea), electrolyte ions (K + , Na + , HCO 3 - and Cl - ), total protein and bilirubin levels were measured in the plasma. The diabetic control exhibited hepato-renal dysfunction with significant (p&lt;0.05) increase in the liver marker enzymes’ activities, total bilirubin, creatinine and urea concentrations while decreasing total protein, albumin and electrolyte ions levels compared with normal control group. Treatment with CAFS supplemented diet significantly (p&lt;0.05) enhanced liver and kidney recovery by reducing the elevated activities of liver marker enzymes, reversed the increments in creatinine, urea and total bilirubin while increasing the concentration of total protein and restoring electrolyte ions concentrations to near normal values. CAFS supplemented diet has hepatic- and renal protective effects on STZ-induced diabetic rats. Thus, CAFS could be considered as therapeutic agent against the progression of diabetes complications. Keywords: Chrysophyllum albidum ; fruit-skin; liver markers; kidney markers; diabetes. DOI: 10.7176/JNSR/10-6-02 Publication date: March 31 st 2020

Hepatoprotective effect of the unsaponifiable matter from olive, linseed and sesame oils against carbon tetrachloride-induced liver injury in rats

In the present study, the hepatoprotective activity of the unsaponifiable matter (UNSAP) of olive oil, linseed, and sesame oils against CCl4-induced liver toxicity in rats was investigated. In a preliminary antioxidant study, UNSAP showed pronounced DPPH radical scavenging activity (IC50 6.2-10.8 mg/mL). The constituents of UNSAP were determined by GC-MS. The subcutaneous administration of CCl4, caused liver injury. The hepatoprotective effect of UNSAP was comparable to that of α-tocopherol, a standard antioxidant agent. The co-administration of the investigated UNSAP normalized the activities of serum marker enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Furthermore, the serum alkaline phosphatase (ALP) activity and hepatic malondialdehyde (MDA) level were found to be alleviated by pre-treatment with the UNSAP. A histopathological evaluation showed marked improvement in the liver of UNSAP- and α-Tocopherol-treated animals. The hepatoprotective effect could be attributed to the antioxidant characteristics of UNSAP.

Ageratum conyzoides L. Protects rat myocardium during isoproterenol-induced myocardial infarction in rats: A biochemical study

This study aimed to evaluate the preventive effect of Ageratum conyzoides L. on cardiac Troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker enzymes, blood glucose, total proteins, albumin/globulin (A/G) ratio, serum uric acid, serum iron, and plasma iron binding capacity in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats treated with ISO(85 mg/kg, administered subcutaneously twice at an interval of 24 h for 2 days) showed a significant increase in the degrees of cardiac troponin T (cTnT), the intensity of the bands of LDH1 and LDH2, and the activities of cardiac diagnostic marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) in serum with a subsequent decrease in the activities of CK, LDH, AST and ALT in the heart. ISO-induced rats showed a significant increase in blood glucose, serum uric acid, and serum iron and a decrease in the levels of total proteins, A/G ratio, and iron binding capacity. Pre-treatment with A. conyzoides L. (100 and 200 mg/kg) daily for a period of 30 days significantly altered the levels of cTnT, the intensity of the bands of LDH1, and LDH2-isoenzyme and the activities of cardiac marker enzymes, and other biochemical parameters. Thus, A. conyzoides L. possesses a cardioprotective effect in ISO-induced oxidative stress in rats.

AMELIORATION OF ACETAMINOPHEN-INDUCED HEPATOTOXICITY USING SOLANUM TORVUM SW. FRUIT EXTRACT IN WISTAR RATS

Objective: Ayurveda and Chinese pharmacopeia have highlighted the traditional medicinal uses of Solanum torvum Sw. The fruits are ethnomedical used in the treatment of liver and spleen enlargement, cough, and also used as a hematopoietic, antimicrobial, and analgesic agent. In the present study, the amelioration of acetaminophen (APAP)-induced hepatotoxicity of the aqueous extract of S. torvum Sw. fruits is evaluated.&#x0D; Methods: The hepatoprotective activity of the fruit extract against APAP insult was evaluated by assessing it is in vivo antioxidants status, membrane-bound adenosine triphosphatases (ATPases), and tricarboxylic acid (TCA) cycle marker enzymes and also through histopathological studies of the liver.&#x0D; Results: Administration of the aqueous fruit extract of the plant caused a significant increase in the in vivo antioxidant status as evident from the reduction in lipid peroxidation caused by APAP and improvement in the mitochondrial membrane stability which is proved from the activity of membrane-bound ATPases and TCA cycle marker enzymes. Histological studies also supported the fact that the plant extract proved to revive the architecture of the toxin damaged liver tissues in par with silymarin. The chemical pathological changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the aqueous extract of S. torvum.&#x0D; Conclusion: The results showed that the extract of S. torvum Sw. fruits has hepatoprotective potential which may be due to the antioxidant activity of its phytoconstituents, especially flavonoids, alkaloids, phenolics, etc.

Thiram-induced cytotoxicity and oxidative stress in human erythrocytes: an in vitro study

Tetramethylthiuram disulfide, commonly known as thiram, is an organosulfur compound which is used as a bactericide, fungicide and ectoparasiticide to prevent disease in seeds and crops. Being a fungicide there is a high probability of human occupational exposure to thiram and also via consumption of contaminated food. In this work, the cytotoxicity of thiram was studied under in vitro conditions using human erythrocytes as the cellular model. Erythrocytes were incubated with different concentrations of thiram (25–500 μM) for 4 h at 37 °C. Control cells (thiram untreated) were similarly incubated at 37 °C. Whole cells and hemolysates were analyzed for various biochemical parameters. Treatment of erythrocytes with thiram increased protein and lipid oxidation and hydrogen peroxide level in hemolysates but decreased glutathione and total sulfhydryl group content. This was accompanied by hemoglobin oxidation, heme degradation and release of free iron. Activities of all major antioxidant enzymes were inhibited. The antioxidant power of thiram treated erythrocytes was lowered resulting in decreased metal reducing and free radical quenching ability. These results suggest that thiram enhances the generation of reactive species that cause oxidative modification of cell components. This was confirmed by experiments that showed enhanced generation of reactive oxygen and nitrogen species in thiram treated erythrocytes. Activities of marker enzymes of glucose metabolism and erythrocyte membrane were also inhibited. All effects were seen in a thiram concentration-dependent manner. Electron microscopy further supported the damaging effect of thiram on erythrocytes. Thus thiram induces oxidative stress condition in human erythrocytes and causes oxidative modification of cell components.

Evaluation of the cardioprotective effect of Casuarina suberosa extract in rats

The aim of the current study was to examine and compare the cardioprotective activities of the chloroform and petroleum extracts the leaves of Casuarina suberosa in isoproterenol (ISO)-induced cardiac tissue oxidative stress. Rats were categorized into 6 groups as follows: control group, vehicle or Tween 80-treated group, ISO-treated group, chloroform extract + ISO treated group, petroleum ether extract + ISO treated group and Reference drug (Captopril) + ISO treated group. ISO injection significantly (p < 0.05) increased the activities of cardiac marker enzymes (CK-MB, LDH, ALT, and AST), cardiac troponin-I, levels of lipid peroxides (MDA), nitric oxide (NO), and vascular endothelial growth factor (VEGF), serum angiotensin-converting enzyme (ACE) activity and neutrophil infiltration marker; myeloperoxidase (MPO) in the cardiac tissues. Pretreatment with chloroform or petroleum ether extracts significantly (p < 0.05) prevented the ISO-induced alteration; they upregulated VEGF expression. Histopathological findings corroborated biochemical results. These extracts exerted a cardioprotective effect by alleviating oxidative stress.

Ferulic acid attenuates arsenic-induced cardiotoxicity in rats.

Arsenic (As), a potent environmental toxin, causes cardiac functional impairments. Ferulic acid (FA), a ubiquitous dietary hydroxycinnamate, exerts beneficial effects on human health. Hence, the present study investigated the effect of FA on myocardial oxidative stress parameters, ATP level, the status of cardiac cytoskeleton intermediate filaments-desmin and vimentin, and AMPK signaling proteins in As-intoxicated rats. Wistar rats were administered orally with FA-40mg/kg and As-5mg/kg alone and in combination for 30 days. Myocardial As content, serum cardiac marker enzyme activities including creatine kinase-isoenzyme, lactate dehydrogenase, and aspartate aminotransferase were increased in As-exposed rats. An accumulation of myocardial oxidants such as reactive oxygen species, lipid peroxidation, nitric oxide, protein carbonyl content, and histological aberrations was observed. A significant decrease of myocardial antioxidants comprises superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and ascorbic acid and declined expression of desmin and vimentin was noted. Impaired energy signaling molecules AMPKα (Thr172), AMPKβ1/2 (Ser108), ACC (Ser79), and intracellular myocardial ATP depletion were observed in As-intoxicated animals. FA attenuates As-induced cardiac dysfunction by restoring the expression of intermediate filaments and AMPK proteins. Based on the above findings, FA treatment could be used as a novel therapeutic against As-induced cardiac dysfunction.

The conservative treatment of ligamentogenic lumbopelvic pain

An increased density of ligaments in the lumbopelvic region, that is typical for ligamentopathy, causes redistribution of the stressstrain state of structures in the biomechanical system «lumbar spine – sacrum – sacroiliac joint – pelvis», thereby provoking development of degenerative-dystrophic changes. Proceeding from the above, the concept of conservative treatment for ligamentogenic lumbopelvic pain (LLPP) should provide restoration of the natural density of the ligament and use of structuremodifying medicines.Objective: to develop a biomechanically and pathogenetically based technology for the conservative treatment of LLPP and assess of the efficacy of its use.Methods: 45 patients with LLPP were divided into three groups: I — extracorporeal shock-wave therapy, II — dietary supplement «Protecta», III — integrated treatment with dietary supplement «Protecta» in combination with shock-wave therapy. The patients’ condition was assessed before the treatment, after 1 and 3 months following its finishing. Results: reduction of the pain and functional limitations was registered in patients from all the groups. Nevertheless the pain, stiffness and functional insufficiency decreased most significantly in cases from group III. Following 1 and 3 months after the end of their treatment course, these patients’ blood serum revealed lower values of destruction in their cartilaginous and osseous tissues as well as a reduced activity of marker enzymes. Biochemical marker values after 1 month following the end of their treatment course in patients from groups I and III were better versus group II, but after 3 months the dynamics of the examined indices were more expressed in groups II and III.Conclusion: the developed technology for conservative treatment of LLPP with use of extracorporeal shock-wave therapy and dietary supplement «Protecta» is effective, as it is confirmed by results of clinical and biochemical studies.

Phytochemistry and Hepatoprotective Activity of Chloroform Extract of NKC Ingredient in Santalum album Against D-Galactosamine Induced Hepatotoxicity in Rats

Objective: Nilavembu Kudineer Chooranam is the combination of nine plant materials. The nine components are Nilavempu (Andrographis paniculata), Vettiver (Vetiveria zizanioides), Vilamiccamver (plectranthus vettiveroides), Santanam (Santalum album), Peyputtal (Trichosanthes dioica), Koraikkilanku (Cyperus rotandus), Cukku (Zingeber officinale), Milaku (Piper nigrum), Parpatakam (Mollugo cerviana). All these plants are used conventionally in the treatment of fever, inflammation, arthralgia, arthritis, gastric ulcer, jaundice, and general weaknes Methods: About 500gm of dried fine powder of Santalum album were soaked in the extractor and macerated for 30 hrs with petroleum ether. On the 22ndday after overnight fast the blood was collected from retro- orbital After the separation of serum from the blood assay of ALT, AST, ALP, γGT and bilirubin were done using standard methods and enzyme assay tests. Results: The preliminary phytochemical analysis of the Chloroform extract of Santalum album reveals the presence of alkaloid, flavonoid, phenol, coumarin, and tannin. The pretreatment of chloroform extract of Santalum album at a dose of 200mg and 400mg/kg (group IV and V) appeared to significantly prevent the galactosamine toxicity as revealed by the hepatic cells which were preserved in cytoplasms. Conclusion: Our findings demonstrated that chloroform extract of Santalum album at both doses possesses hepatoprotective and antioxidant activity, which is evidenced by lowered serum hepatic marker enzyme activities. Among the two dosages tested, 400 mg/kg/body weight showed more promising hepatoprotective and antioxidant activity, and is comparable to the standard drug Silymarin. Keywords: Nilavembu Kudineer Chooranam, Chloroform extract of Santalum album, preliminary phytochemical analysis, Hepatoprotective activity, D-Galactosamine induced hepatotoxicity in rats.

Biological and Phytochemical Screening of Fumaria indica extract on Chemically Induced Hepatocellular Carcinoma with Reference to Biochemical Parameters

Liver disease or liver cancer is the sixth most common cancer and the third leading cause of cancer mortality in the world. Hepatitis viral infection, food additives, alcohol, fungal toxins (aflatoxins), toxic industrial chemicals, air and water pollutants are the major risk factors of liver cancer. Moreover, due to high tolerance of liver, HCC is seldom detected at an early stage and once detected treatment faces a poor prognosis in most cases.Fumaria indica possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Fumaria indica would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Fumaria indicais very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of a Fumaria indicaof 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt. Fumaria indica extract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Fumaria indicaextract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats. In addition to this, studies on molecular aspect of hepatoprotective therapy will give mechanistic information in hepatoprotective therapy and also critical balance should be there between the animal model and clinical research. The hepatoprotective properties of Fumaria indicashould provide useful information in the possible application in hepatic liver disease.

The Effect of Oral Intake of Sodium Benzoate on the Activity of Liver Marker Enzymes and Electrolyte Level of the Wistar Albino Rats

The in vivo effect of oral administration of varying concentrations (150, 250, 500 mg/kg body wt) of sodium benzoate (a known preservative in the food, cosmetic and pharmaceutical industry) on serum liver marker enzyme activity and electrolyte levels of wistar albino rats were investigated. The oral intake was administered at 24 hour intervals for 7, 14, 21 and 28 days. The groups were labeled; control (group 1), 7days (group 2), 14days (group 3), 21 days (group 4) and 28days (group 5). The rats were fed normal diet ad libitum and blood sample for the determination was taken at the end of the duration. For serum electrolytes, the result obtained for sodium benzoate concentrations administered showed significant (p≤0.05) increase in sodium (Na+) for groups 3, 4 and 5 for 150 mg/kg body wt. and group 2, 3, 4 and 5 for 250 mg/kg body wt and 500mg/kg body wt. of experimental rats. Chloride (Cl-) showed significant (p≤0.05) increase at all administered groups for 250 mg/kg and 500mg/kg. Potassium (K+) was only significantly increased at group 5 for 500mg/kg body wt. while for bicarbonate (HCO3) it showed no significant change in all treated groups. Values were all compared to the control. For liver marker enzymes, sodium benzoate significantly increased (p≤0.05) aspartate transaminase (AST) activity of experimental rats in groups 2, 3, 4 and 5 of 250 mg/kg body wt. and 500mg/kg body wt., alanine transaminase (ALT) showed significant increase (p≤0.05) in group 4 and 5 for 250 mg/kg body wt and group 2, 3, 4 and 5 for 500 mg/kg body wt., alkaline phosphatase (ALP) showed significant (p≤0.05) increase in group 2, 3, 4 and 5 for 500 mg/kg body wt.These findings suggest possible changes in blood chemistry due to the preservative.

Protective effects of catalpol on diabetes mellitus-induced male reproductive damage via suppression of the AGEs/RAGE/Nox4 signaling pathway

AimsDiabetes mellitus (DM)-induced reproductive damage is an important cause of infertility for male DM patients, we herein evaluated the effects of catalpol on diabetic reproductive damage through the suppression of the AGEs/RAGE/Nox4 signaling pathway. MethodsKK-Ay diabetic reproductive damage mice were administered with catalpol for 8 weeks, the testis/body weight ratio, testicular histopathology, the levels of endogenous hormone and the activity of testicular marker enzymes were determined. In vitro, the GC-2 cell injury model was induced by advanced glycation end-products (AGEs) and pretreated with catalpol. Cell viability, apoptosis, and oxidative stress markers were detected and the mechanism based on the AGEs/RAGE/Nox4 pathway was explored. Key findingsCatalpol showed remarkable capacity on protecting diabetic reproductive damage by improving the histomorphology of the testes, increasing the testis/body weight ratio and activity of acid phosphatase (ACP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (γ-GT). The reduced testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in DM mice were also reversed with catalpol intervention. Moreover, catalpol showed markedly effects of anti-oxidative in vivo and in vitro, which significantly down-regulated reactive oxygen species (ROS) levels and restored superoxide dismutase (SOD) activity, meanwhile decreased GC-2 cell apoptosis and Bax/Bcl-2 ratio. Moreover, the over-expression of receptors for AGEs (RAGE), NADPH oxidase type 4 (Nox4) and phosphorylation of nuclear transcription factor-κB p65 (NF-κB p65) were suppressed by catalpol. SignificanceCatalpol could alleviate DM-induced male reproductive damage by inhibiting oxidative stress-induced apoptosis and inflammation mediated by AGEs/RAGE/Nox4 signaling pathway.

Piceatannol inhibits oxidative stress through modification of Nrf2-signaling pathway in testes and attenuates spermatogenesis and steroidogenesis in rats exposed to cadmium during adulthood.

BackgroundCadmium (Cd) is considered a heavy metal and potential pollutant to the environment.PurposeThe purpose of this study was to evaluate the protective potential of piceatannol (PT; 10 mg/kg body weight/day) against cadmium (Cd; 5 mg/kg body weight/day)-induced testicular dysfunction in Wistar rats.Materials and methodsRats were randomly divided into four groups: control, PT, Cd, and Cd + PT.ResultsTreatment with Cd resulted in a significant decrease in body, testicular, and epididymal weights, sperm quantity and quality, steroidogenic marker–enzyme activities, mRNA- and protein-expression levels of SF1, StAR, and P450 side chain–cleaving enzyme, and serum male sex hormonal levels when compared to controls. Testicular malondialdehyde levels were significantly increased, with a significant reduction in enzymatic and nonenzymatic antioxidants in Cd-treated rats compared to control rats. Testicular histomorphometric results supported the biochemical and molecular alterations observed in the study. In addition, significant downregulation in mRNA- and protein-expression levels of cytosolic Nrf2, HO1, γGCS, GPx, and NQO1, as well as significant upregulation in mRNA- and protein-expression levels of Nrf2 and Keap1 in testicular tissue, were noticed in rats administered Cd. PT treatment inCd-treated rats caused marked alleviation in body and organ weights, sperm analysis, steroidogenesis, serum hormonal levels, histomorphometric changes, and oxidative and antioxidative status in testes when compared to Cd alone–treated rats. Further, treatment of rats with PTl showed a marked improvement in mRNA- and protein-expression levels of Nrf2 and its regulated genes and proteins.ConclusionThe present study provides compelling evidence that PT treatment results in significant protection against Cd-induced testicular dysfunctions, such as spermatogenesis, steroidogenesis, and oxidative stress in rats, possibly through modification of the Nrf2–Keap1 signalling pathway.

Using complex II as an emerging therapeutic target for the treatment of muscle lesions

After patients has been trapped into skeletal muscle injury, hypoxic and dysfunctional mitochondria brings about a crisis in energy supply that severely disrupts the repair of skeletal muscle. This study aims to elucidate injury-induced adaptations in the mitochondria and provide statistics for the role of complex II in instilling cells with energy under hypoxic conditions. Fifty-six male Wistar rats were divided into control, 12 h, 2 d, 5 d, 7 d, 10 d, 15 d, and 30 d postinjury groups. Contusion injury was made via an instrumented drop-mass technique delivering single impact to the posterior surface of the gastrocnemius of one limb of the rats. ROS levels, loss of mitochondrial membrane potential (MMP), activities of marker enzymes (miCK, LDH, and ALP), and activities of complexes I–III were determined. Our findings reveal that the first 2 d postinjury, especially at 12 h, is the period with most severe oxidative stress. After injury, the activities of mitochondrial complexes I–III display different behaviors based on time and various energy production mechanisms. Our results highlight that complex II participates in electron transport in the acute phase of blunt trauma. We proposed that CII could be a therapeutic target in muscle lesions.

Effect of angiolin on the functional state of the liver in experimental steatohepatitis

For a real impact on the functional state of the liver in steatohepatitis, the appointment of metabolic correctors is suggested. The aim of the study is to evaluate the effect of the biologically active compound angiolin on markers of cytolysis and liver function in experimental nonalcoholic steatohepatitis. Experimental studies were performed on 110 white, non-linear, mature male rats weighing 180–200 g at the start of the experiment. A model of non-alcoholic steatohepatitis was created, rats were maintained for 8 weeks on a high-calorie, high-cholesterol diet. After creating the model some of the animals were transferred to a standard semi-synthetic starch-casein diet and administered for 4 weeks the biologically active compound Angiolin. The activity of enzyme markers of cytolysis — alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGT) in serum was determined by standard methods. Liver biosynthetic function was assessed by the level of total protein and albumin. Statistical analysis of the obtained results was carried out with the use of the license program “STATISTICA 8” by Statsoft. After creating a model of non-alcoholic fatty liver disease in rats, an increase in body mass index occurred, high activity of ALT, AST, GGT was manifested and the concentration of total protein and albumin in the blood serum decreased compared to intact animals. An inverse correlation of mean strength was found between body mass index and total protein concentration as well as serum albumin. A strong inverse correlation between the value of ALT activity and the concentration of total protein and albumin in blood serum was established. The use of angiolin contributed to an increase in the concentration of total protein and albumin in the blood serum, an increase in the albumin / globulin coefficient, and a decrease in cytolysis. It was concluded that the biologically active compound angiolin positively affects the parameters of cytolysis and protein synthesis of the liver.

Biological and Phytochemical Screening of Tephrosia purpurea extract on Chemically Induced Hepatocellular Carcinoma with Reference to Biochemical Parameters

Tephrosia purpurea possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Tephrosia purpurea would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Tephrosia purpurea is very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of aTephrosia purpurea of 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt.Tephrosia purpureaextract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Tephrosia purpurea extract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats.