The effect of tyrosol on diclofenac sodium-induced acute nephrotoxicity in rats.

Although diclofenac (DCF) is a nonsteroidal anti-inflammatory drug that is considered safe, its chronic use and overdose may show some toxic effects. The protective effect of tyrosol (Tyr) pretreatment against DCF-induced renal damage was investigated in this study. The 32 rats used in the study were randomly divided into four groups of eight rats each. According to the data obtained, it was determined that creatinine, urea, and blood urea nitrogen (BUN) levels increased in serum samples of the DCF group. Besides, the levels of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity decreased and the malondialdehyde (MDA) level increased in the kidney tissue. However, no change was observed in catalase (CAT) activity. Cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (Tnf-α) levels increased and nuclear factor erythroid 2-related factor 2 (Nrf-2) levels decreased. No change was detected in the level of interleukin 1 beta (IL-1ß). When the DCF+Tyr group and the DCF group were compared, it was assessed that Tyr had a curative effect on all biochemical parameters. Also, kidney damages, such as degeneration and necrosis of tubular epithelium and congestion of veins, were obviated by treatment with tyrosol in histopathological examinations. It was determined that Tyr pretreatment provided a protective effect against nephrotoxicity induced by DCF with its anti-inflammatory and antioxidant properties.

Carvacrol showed a curative effect on reproductive toxicity caused by Bisphenol AF via antioxidant, anti-inflammatory and anti-apoptotic properties.

Bisphenol AF (BPAF) is an endocrine disruptor, and human exposure to these chemicals is growing in industrialized nations. BPAF has been demonstrated in studies to have toxic effects on reproductive health. This study examined the effects of oral exposure to BPAF on the reproductive system and the protective effects of carvacrol in rats. From 32 Wistar albino rats, four separate groups were set up for this purpose. Carvacrol 75 mg/kg and BPAF 200 mg/kg were administered by oral gavage method. Rat sperm parameters and serum testosterone levels were measured after 28 days of administration. The study looked at the MDA in the testis tissues, as well as CAT, GPx, and GSH as antioxidants parameters, NF-κB and TNF-α as inflammatory markers, caspase-3 and Bcl-2 as apoptosis parameters, and PCNA as cell proliferation markers. In addition, testis tissues underwent histological evaluation. As a result, in rats exposed to only BPAF, sperm counts declined, testosterone levels reduced, oxidative stress, inflammation, and apoptosis increased, and cell proliferation decreased. Furthermore, severe disruptions in tissue architecture and decreased spermatogenesis were reported. In contrast, sperm parameters improved, testosterone levels increased, oxidative stress and inflammation decreased, and apoptosis was prevented in the carvacrol-treated group compared to the BPAF-only group. It was also found that spermatogenesis was maintained, and structural abnormalities in testicular tissue were mostly avoided with an increase in PCNA expression. According to the findings, despite BPAF-induced testicular and reproductive toxicity, carvacrol had therapeutic potential due to its anti-inflammatory, antioxidant, cell proliferation-increasing, and anti-apoptotic activities.

Assessment of Anticholinergic and Antidiabetic Properties of Some Natural and Synthetic Molecules: an In Vitro and In Silico Approach.

INTRODUCTION: In this study, it was aimed to determine the in vitro and in silico effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. BACKGROUND: Alzheimer's disease (AD) and Type II diabetes mellitus (T2DM), which are considered amongst the most important diseases of today's world. However, the side effects of therapeutic agents used in both diseases limit their use. Therefore, it is important to develop drugs with high therapeutic efficacy and better pharmacological profile. OBJECTIVE: This study sets out to determine the related enzyme inhibitors used in the treatment of AD and T2DM, which are considered amongst the most important diseases of today's world. METHODS: In the current study, the in vitro and in silico effects of dienestrol, hesperetin, L-thyroxine, 3,3',5-Triiodo-L-thyronine (T3) and dobutamine molecules on AChE, BChE and α-glycosidase enzyme activities were investigated. RESULTS: All the molecules showed an inhibitory effect on the enzymes. The IC50 and Ki values of the L-Thyroxine molecule, which showed the strongest inhibition effect for the AChE enzyme, were determined as 1.71 µM and 0.83±0.195 µM, respectively. In addition, dienestrol, T3 and dobutamine molecules showed a more substantial inhibition effect than tacrine. Dobutamine molecule showed the most substantial inhibition effect for BChE enzyme, and IC50 and Ki values were determined as 1.83 µM and 0.845±0.143 µM, respectively. The IC50 and Ki values for the hesperetin molecule, which showed the strongest inhibition for the α-glycosidase enzyme, were determined as 13.57 µM and 12.33±2.57 µM, respectively. CONCLUSION: According to the results obtained, it may be said that the molecules used in the study are potential inhibitor candidates for AChE, BChE and α-glycosidase.

Enzyme Inhibition and Antioxidant Activities of Asparagus officinalis L. and Analysis of Its Phytochemical Content by LC/MS/MS.

In the study, water, ethanol, methanol, dichloromethane, and acetone extracts of Asparagus officinalis L. were obtained by maceration. DPPH⋅, ABTS⋅+ , FRAP, and CUPRAC methods determined the antioxidant capacities of all extracts. Moreover, the in vitro effects of extracts on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase (CA)-I, CA-II and α-Glycosidase were investigated. At a 10 µg/ml concentration, the extract with the highest Fe3+ reduction capacity was ethanol (AE), and the extract with the highest Cu2+ reduction capacity was acetone (AA). AE for AChE (IC50 =21.19 µg/ml) and α-Glycosidase (IC50 : 70.00 µg/ml), methanol (AM) for BChE (IC50 =17.33 µg/ml), CA-I and II (IC50 =79.65 and 36.09 µg/ml, respectively) showed the most potent inhibition effect. The content analysis of acetone extract was performed with LC/MS-MS, the first three phytochemicals found most were p-Coumaric acid, rutin, and 4-hydroxybenzoic acid (284.29±3.97, 135.39±8.19, and 102.06±5.51 µg analyte/g extract, respectively).

Investigation of the effects of safranal on the experimentally created rheumatoid arthritis model in rats.

Rheumatoid arthritis (RA) is a systemic chronic disease characterized by inflammation and synovitis. More effective treatment methods with less side effects need to be developed. In this context, current study investigated the therapeutic effects of safranal in a model of complete Freund's adjuvant (CFA)-induced RA. The control group was given 1 ml of saline orally starting from the 8th day, and 0.2 ml of CFA was given to the RA, RA + Safranal and RA + Methotrexate (MTX) groups on the 0th day of the experiment. Starting from the 8th day of the experiment, 1 ml of saline was given to the RA group, safranal was given at 200 mg/kg of body weight to the RA + MTX group, and 3 mg/kg of MTX to the RA + MTX group twice a week. The results showed that weight gain decreased in the RA group compared to the control group while arthritis index score, thymus index, and planter temperature were found to be increased. Additionally, a deterioration in blood parameters, an increase in alanine aminotransferase, aspartate aminotransferase, urea, creatinine, C-reactive protein, and malondialdehyde levels, and a decrease in reduced glutathione levels and glutathione peroxidase and catalase (CAT) activities were seen while tumor necrosis factor-α, interleukin-6 (IL-6), cyclooxygenase-2, nuclear factor kappa B levels were found to be increased. However, the safranal had a regulatory effect on all the values, except IL-6 and CAT, and blood parameters. Moreover, histopathological examination revealed that safranal reduced inflammatory cell infiltration and edema.

Protective effect of Smilax excelsa L. pretreatment via antioxidant, anti-inflammatory effects, and activation of Nrf-2/HO-1 pathway in testicular torsion model.

The protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-α and NF-κB levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. PRACTICAL APPLICATIONS: Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.

Some phenolic natural compounds as carbonic anhydrase inhibitors: An in vitro and in silico study.

This paper presents experimental and molecular docking studies on the inhibitory effects of tyrosol, hydroxytyrosol, luteolin, diosmetin, caffeic acid, luteolin 7-O-glycoside, and apigenin 7-O-glycoside from olive (Olea europaea L.) leaf against human carbonic anhydrase (hCA, E.C.4.2.1.1) isozymes I and II. After these isozymes were separately purified, their activities were determined using the esterase activity. IC50 values for hCA I and II were calculated as 2.02-11.38 µM and 2.23-9.05 µM, respectively. The compounds were identified as CA inhibitors, with Ki values in the ranges of 1.66-9.17 µM for the hCA I isozyme and 1.49-14.21 µM for hCA II. The inhibitory effects of these natural compounds were also compared to acetazolamide, which is a potent inhibitor of both CA isozymes. Our results may contribute to the synthesis of new CA inhibitors and pave the way for new drug design in the treatment of a number of diseases including cancer, obesity, diabetes, and glaucoma.

Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats.

The clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.

Oleuropein and Verbascoside - Their Inhibition Effects on Carbonic Anhydrase and Molecular Docking Studies.

Recently, carbonic anhydrase (CA, E.C.4.2.1.1) inhibitors from natural product have paved the way for novel drug design in the treatment and prevention of some global diseases such as glaucoma, diabetes, and cancer. For this purpose, the inhibition effects of oleuropein and verbascoside from olive (Olea europaea L.) oil on human carbonic anhydrase I, and II (hCA I, and II) isoenzymes were evaluated in the current study. The inhibition effects of both natural compounds were determined by the esterase activity (in vitro). IC50 value of oleuropein and verbascoside was calculated as 1.57 and 1.73 µM for hCA I isoenzyme, respectively. At the same manner, K i values were determined as 1.25 ± 0.42 and 2.00 ± 0.42 µM, respectively. Then, IC50 value of each compound for hCA II isoenzyme was calculated as 2.23 and 1.90 µM, respectively. Similarly, K i values were determined as 2.37 ± 0.87 µM and 1.49 ± 0.33 µM, respectively. Also, the inhibitory effects and potent binding mechanisms of oleuropein and verbascoside on hCA I, and II isoenzymes were realized by molecular docking studies. Consequently, both natural phenolic compounds demonstrated the potent inhibition profiles against the both isoenzymes. Therefore, we believe that these results may break new ground in the drug development for the treatment of some global disorders.

Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation.

Asthma is an inflammatory disease that affects many people around the world, especially persons at paediatric age group. The effectiveness of tyrosol, a natural phenolic compound, was examined in the asthma model induced by ovalbumin (OVA). For this purpose, four groups, each consisting of eight rats, were arranged. For 21 days, physiological saline solution was treated to the control group and OVA was treated to the groups of OVA, OVA + dexamethasone (Dexa) and OVA + tyrosol groups, intraperitoneally and through inhalation. Additionally, 0.25 mg/kg Dexa was treated to the OVA + Dexa group and 20 mg/kg tyrosol to the OVA + tyrosol group by oral gavage. Serum, blood, bronchoalveolar lavage fluid (BALF) and lung tissues of the rats were examined. It was observed that MDA level decreased, GSH level and GPx activity increased, and there was no change in CAT activity in lung tissues of the tyrosol treatment groups. It was also observed that NF-κB, TNF-α, IL-4, IL-5, IL-13, IFN-γ and IgE levels decreased compared to the OVA group in lung tissue and serum samples except for serum NF-κB and IL-4. However, no effect on IL-1 ß level was observed. In addition, it was determined that tyrosol treatment increased the IL-10 level on both tissue samples. The results of the histopathological investigation of lung tissue showed that tyrosol significantly ameliorated OVA-induced histopathological lesions. Additionally, PAS staining showed that mucus hypersecretion was significantly reduced with the use of tyrosol. In addition, it was determined that the number of eosinophils decreased significantly in blood and BALF samples. The obtained results showed that tyrosol possessed antioxidant and anti-inflammatory features on OVA-induced rats and preserved tissue architecture.

The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats.

One of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3 ) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3 -treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3  + ESC groups, and NF-κB increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3  + ESC group compared to AlCl3 group. It was also determined that AlCl3 -induced tissue injury was significantly prevented by ESC co-treatment.

Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin.

In the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO2, SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1ß), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.

Evaluation of the effects of Cyclotrichium niveum on brain acetylcholinesterase activity and oxidative stress in male rats orally exposed to lead acetate.

Cyclotrichium niveum is an endemic plant for Turkey and it appears to have in vitro antioxidant and acetylcholinesterase inhibition properties. To the best of our knowledge, there has been no study on the in vivo effects of this plant. Therefore, the purpose of this study was to evaluate the effects of C. niveum on lead (Pb)-acetate-induced potential alterations in brain acetylcholinesterase activity, as well as oxidative stress in male rats. The rats were randomly assigned to control, Pb-acetate, C. niveum and Pb-acetate+ C. niveum groups. Pb-acetate was provided in drinking water (500 ppm), and C. niveum was administered via orogastric gavage (4 ml/kg) for 30 days. The acetylcholinesterase activity in the brain significantly decreased only in the Pb-acetate group. The malondialdehyde level significantly increased, and the reduced glutathione activity decreased in the Pb-acetate group. The reduced glutathione and glutathione-S-transferase activities of the C. niveum group were higher than the control group. No Pb was detected on a ppb level in the brain tissue of the control and C. niveum groups, while it was detected in the brains of the rats in the Pb-acetate and Pb-acetate+ C. niveum groups (185+8.98 ppb and 206+56.65 ppb, respectively). The data collected in this study suggested that C. niveum may reduce inhibition of brain AChE activity and oxidative stress against Pb-acetate-induced alterations in the brain of male rats.

Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats.

Although Doxorubicin (DOX) is a widespread drug used in the treatment of cancer, its clinical use is restricted due to its common side effects. In addition, administrating DOX with an antioxidant has recently become a new strategy in preventing the side effects of DOX. The protective effects of morin, a natural flavonoid, against DOX-induced liver and kidney damage in rats were investigated biochemically, immunohistochemically and histopathologically in this study. The experimental procedure was planned as 10 days, and 5 groups consisting of seven rats were formed. Morin was given orally to rats at a dose of 50 and 100 mg/kg for 10 days and DOX was given a single dose of 40 mg/kg intraperitoneally on day 8. In order to determine the protective effect of morin against oxidative stress caused by DOX, reduced glutathione (GSH) and malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activities were measured in liver and kidney tissues. Liver and kidney tissue damage were determined both histopathologically and by serum alanine transaminase (ALT), aspartate transaminase (AST), urea and creatinine analysis. In order to determine the effect of DOX-induced inflammation and against the effect of morin, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and nuclear factor kappa B (NF-κB) levels were determined in both tissues. Liver and kidney B-cell lymphoma-2 (Bcl-2) levels were determined biochemically. In addition, Bax expression in liver tissue and aquaporin-2 (AQP-2) and nephrin expression in renal tissue were determined immunohistochemically. It was determined that oxidative damage caused by DOX decreased and improvement of liver and kidney function markers were observed in the groups that were treated with morin. In addition, pre-treatment of morin showed a regulatory effect on TNF-α, IL-1ß and NF-κB levels. It prevented the increase in DOX-induced Bax expression and decrease in Bcl-2 level, AQP-2 and nephrin expression. Histopathological examination revealed that it prevented tissue damage in liver and kidney tissues.

Protective Effect of Hesperidin on Sodium Arsenite-Induced Nephrotoxicity and Hepatotoxicity in Rats.

The present study was conducted to investigate the protective effects of hesperidin (HSP) against sodium arsenite (SA)-induced nephrotoxicity and hepatotoxicity in rats. Thirty-five male Sprague Dawley rats were divided into five groups as follows: control, HSP, SA, SA + HSP 100, and SA + HSP 200. Rats were orally gavaged with SA (10 mg/kg body weight) and HSP (100 and 200 mg/kg body weight) for 15 days. SA increased oxidative damage by decreasing antioxidant enzyme activities, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and glutathione (GSH) level and increasing malondialdehyde (MDA) level in the kidney and liver tissues. In addition, it increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and serum urea and creatinine levels. Furthermore, SA caused inflammation, apoptosis, and oxidative DNA damage by increasing tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1ß (IL-1ß), cysteine aspartate-specific protease-3 (caspase-3), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the kidney and liver tissues and by increasing liver p53 and kidney interleukin-6 (IL-6) expressions. In other words, HSP administration reduced apoptosis, oxidative stress, inflammation, and oxidative DNA damage significantly in SA-induced kidney and liver tissues depending on dose. In this study, it was seen that HSP showed a protective effect against SA-induced kidney and liver toxicity.

Morin attenuates doxorubicin-induced heart and brain damage by reducing oxidative stress, inflammation and apoptosis.

Doxorubicin (DOX) is an effective antineoplastic agent of the anthracycline group. However, as with most anticancer drugs, they cause some toxic effects, including major cardiotoxicity and cognitive impairment. In this study, protective effects of morin against DOX-induced cardiotoxicity and neurotoxicity in rats were investigated. Morin was orally administered to rats at a dose of 50 and 100 mg/kg body weight for 10 days. DOX was administered 40 mg/kg body weight by single dose intraperitoneal injection on the 8th day of the study. Both the levels of glutathione (GSH) and malondialdehyde (MDA) were assessed and enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were assessed to determine the protective effect of morin against oxidative stress. To determine the anti-inflammatory effect, the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), nuclear factor kappa B (NF-κB) were assessed in the heart and brain tissues. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CKMB) activities, which are cardiac function markers, and cardiac troponin-I (cTn-I) levels were also determined. Anti-apoptotic effect was determined by anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and pro-apoptotic protein cysteine aspartate specific protease-3 (caspase-3) changes. The regulatory role of morin in signal transduction in the brain tissue was assigned with the determination of amount of acetylcholinesterase (AChE), and its healing effect on the central nervous system was determined with imuinohistochemical detection of glial fibrillar acidic protein (GFAP) level. Histopathological evaluation of heart and brain tissues was performed in all groups.

Inhibitory properties of some heavy metals on carbonic anhydrase I and II isozymes activities purified from Van Lake fish (Chalcalburnus Tarichi) gill.

In this study, CA I and II isoenzymes were purified from Van Lake fish gills by using Sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography and to determine the effects of some metals on the enzyme activities. For purified CA I isoenzyme, yield, specific activity, and purification fold were obtained as 42.07%, 4948.12 EU/mg protein, and 116.61 and for CA II isoenzyme, 7%, 1798.56 EU/mg protein, and 42.38 respectively. Activity of CA was determined by measuring "CO2-hydratase activity". Purity control was checked by SDS-PAGE. In vitro inhibitory effect of Cu2+, Ag+, Cd2+, Ni2+ metal ions, and arsenic (V) oxide were also examined for both isozymes activities. Whereas Cu2+, Ag+, Cd2+, and Ni2+ ions showed inhibitory effects on both isozymes, arsenic (V) oxide showed activation effect. IC50 values were calculated by drawing activity %-[I] graphs for metal ions exhibiting inhibitory effects. IC50 values were determined as 3.39, 6.38, 13.52, and 206 µM for CA I isozyme and 6.16, 20.29, 46, and 223 µM for CA II isozyme respectively.

Role of geraniol against lead acetate-mediated hepatic damage and their interaction with liver carboxylesterase activity in rats.

In this study, the effect of geraniol (50 mg/kg for 30 d), a natural antioxidant and repellent/antifeedant monoterpene, in a rat model of lead acetate-induced (500 ppm for 30 d) liver damage was evaluated. Hepatic malondialdehyde increased in the lead acetate group. Reduced glutathione unchanged, but glutathione S-transferase, glutathione reductase, as well as carboxylesterase activities decreased in geraniol, lead acetate and geraniol + lead acetate groups. 8-OhDG immunoreactivity, mononuclear cell infiltrations and hepatic lead concentration were lower in the geraniol + lead acetate group than the lead acetate group. Serum aspartate aminotransferase and alanine aminotransferase activities increased in the Pb acetate group. In conclusion, lead acetate causes oxidative and toxic damage in the liver and this effect can reduce with geraniol treatment. However, we first observed that lead acetate, as well as geraniol, can affect liver carboxylesterase activity.

Compounds from Terminalia mantaly L. (Combretaceae) Stem Bark Exhibit Potent Inhibition against Some Pathogenic Yeasts and Enzymes of Metabolic Significance.

Background: Pathogenic yeasts resistance to current drugs emphasizes the need for new, safe, and cost-effective drugs. Also, new inhibitors are needed to control the effects of enzymes that are implicated in metabolic dysfunctions such as cancer, obesity, and epilepsy. Methods: The anti-yeast extract from Terminalia mantaly (Combretaceae) was fractionated and the structures of the isolated compounds established by means of spectroscopic analysis and comparison with literature data. Activity was assessed against Candida albicans, C. parapsilosis and C. krusei using the microdilution method, and against four enzymes of metabolic significance: glucose-6-phosphate dehydrogenase, human erythrocyte carbonic anhydrase I and II, and glutathione S-transferase. Results: Seven compounds, 3,3'-di-O-methylellagic acid 4'-O-α-rhamnopyranoside; 3-O-methylellagic acid; arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid; arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside; 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid; stigmasterol; and stigmasterol 3-O-ß-d-glucopyranoside were isolated from the extract. Among those, 3,3'-di-O-methylellagic acid 4'-O-α-rhamnopyranoside, 3-O-methylellagic acid, and arjunglucoside showed anti-yeast activity comparable to that of reference fluconazole with minimal inhibitory concentrations (MIC) below 32 µg/mL. Besides, Arjunglucoside potently inhibited the tested enzymes with 50% inhibitory concentrations (IC50) below 4 µM and inhibitory constant (Ki) <3 µM. Conclusions: The results achieved indicate that further SAR studies will likely identify potent hit derivatives that should subsequently enter the drug development pipeline.