Kidney Enzyme Research Articles

Serum biochemical evaluation following administration of imidazolyl thiazolidinedione in streptozotocin-induced diabetic rats.

Diabetes mellitus represents a prominent global health concern, characterized by a rising prevalence rate. Type 2 Diabetes Mellitus (T2DM) is purported to be associated with an intricate interplay of genetic, environmental, and lifestyle factors. While some progress have been made in T2DM management, controlling associated complications remains a great challenge in medicine. This study investigated a synthesized Imidazolyl Thiazolidinedione antidiabetic agent (PA9), focusing on serum parameters. Streptozotocin-induced diabetic rats (n = 6) were subjected to orally treatment with PA9 (synthesized by Shakour et al. in an equal dose of a standard drug, 0.011mmol/kg). The study conducted to measure some specific serum factors, including lipid profiles, liver and kidney enzymes, cardiac enzymes, and oxidative stress markers, both before and after treatment. The study findings indicated that PA9 effectively ameliorates hyperlipidemia by significantly reducing total cholesterol and triglyceride levels in serum. Additionally, PA9 demonstrated hepatoprotective effects against TZD-induced injuries, as evidenced by decreased levels of alanine transaminase and, alkaline phosphatase. In addition, PA9 also exhibited a modulatory effect on a cardiac injury marker, creatine kinase MB. Moreover, PA9 demonstrated antioxidant properties by reducing oxidative stress markers and enhancing the activities of catalase, thiol, and superoxide dismutase. The synthesized TZD compound (PA9) stands out as a highly promising agent for the management of diabetes. Its significant antihyperlipidemic effects, preventive influences on organ injuries, and demonstrated efficacy in reducing oxidative stress marker (SOD) make it therapeutic agent in diabetes management. This study lays the groundwork for innovative strategies in diabetes management.

Impact of graded doses of enrofloxacin on the safety and biological responses of Nile tilapia Oreochromis niloticus

The cultivation of tilapias, the third most farmed fish group globally, has been rapidly growing, especially in Southeast Asia. This surge in tilapia farming intensification has led to increased use of antibiotics to control bacterial diseases. This study investigated the safety implications of administering graded doses of enrofloxacin (ENF) at 0 (control), 10, 30, 50 and 100 mg/kg biomass/day orally to Oreochromis niloticus. The 43-day study comprised 7 days of pre-dosing, 15 days of ENF-dosing, and a 21-day recovery period with a periodical assessment of the biological responses of fish. The results revealed that the overdosed groups experienced up to 21% reduction in feed consumption, 11% mortalities, and adverse impacts on hematology, including a decrease in erythrocytes, and monocytes and an increase in leukocytes, thrombocytes, lymphocytes, and neutrophils. Haematological indices like mean corpuscular volume and mean corpuscular hemoglobin decreased, while mean corpuscular hemoglobin concentration increased. The plasma biochemical parameters including glucose and liver and kidney enzymes unveiled a significant dose- and time-dependent increase, while calcium and chloride levels decreased. Erythrocytes displayed several erythrocyte cellular and nuclear abnormalities. The frequency of micronucleus increased with dose and time, suggesting potential genotoxicity of ENF. Additionally, a dose-dependent increase in residues in the tissues with the highest accumulation in muscle was documented. Nevertheless, the recovery of the measured parameters upon dose termination indicated that the ENF-induced alterations are reversible. The study affirmed the safety of ENF at the recommended dose (10 mg) in O. niloticus and their adoptive responses to higher doses.

Hesperidin Nanoformulation: A Potential Strategy for Reducing Doxorubicin-Induced Renal Damage via the Sirt-1/HIF1-α/VEGF/NF-κB Signaling Cascade.

Hesperidin (Hes) functions as a strong antioxidant and anti-inflammatory to guard against damage to the heart, liver, and kidneys. Nevertheless, due to its restricted solubility and bioavailability, a delivery method is required for it to reach a specific organ. In this study, ion gelation was used to synthesize a chitosan/hesperidin nanoformulation. Numerous characterization techniques, such as zeta potential, particle size, XRD, TEM, SEM, and FTIR analyses, were used to corroborate the synthesis of hesperidin nanoparticles (Hes-NPs). Male albino mice were given a pretreatment dose of 100 mg/kg, PO, of Hes or Hes-NPs, which was administered daily for 14 days before the induction of doxorubicin nephrotoxicity on the 12th day. Kidney function (urea and creatinine levels) was measured. Lipid peroxidation (MDA) and antioxidant enzyme (CAT and SOD) activities were estimated. TNF-α, IL-1β, and VEGF content; histopathological examination of kidney tissue; and immunohistochemical staining of NF-κB, Caspase-3, BAX, Bcl-2, and TGF-β1 were evaluated. The gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were also considered. The results showed that pretreatment with Hes or Hes-NPs reduced doxorubicin's nephrotoxic effects, with Hes-NPs showing the greatest reduction. Kidney enzyme and MDA content were lowered in response to the Hes or Hes-NP pretreatment, whereas antioxidant enzyme activities were increased. Hes or Hes-NP pretreatment suppressed the levels of TNF-α, IL-1β, VEGF, NF-κB, Caspase-3, BAX, and TGF-β1; however, pretreatment increased Bcl-2 protein levels. Furthermore, the gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were considerably higher with Hes-NP than with Hes treatment. These results suggest that Hes-NP treatment might reduce DOX-induced nephrotoxicity in mice via modulating Sirt-1/HIF1-α/VEGF/NF-κB signaling to provide antioxidant, anti-inflammatory, and anti-apoptotic effects.

Amino acid metabolism in kidney health and disease.

Amino acids form peptides and proteins and are therefore considered the main building blocks of life. The kidney has an important but under-appreciated role in the synthesis, degradation, filtration, reabsorption and excretion of amino acids, acting to retain useful metabolites while excreting potentially harmful and waste products from amino acid metabolism. A complex network of kidney transporters and enzymes guides these processes and moderates the competing concentrations of various metabolites and amino acid products. Kidney amino acid metabolism contributes to gluconeogenesis, nitrogen clearance, acid-base metabolismand provision of fuel for tricarboxylic acid cycle and urea cycle intermediates, and is thus a central hub for homeostasis. Conversely, kidney disease affects the levels and metabolism of a variety of amino acids. Here, we review the metabolic role of the kidney in amino acid metabolism and describe how different diseases of the kidney lead to aberrations in amino acid metabolism. Improved understanding of the metabolic and communication routes that are affected by disease could provide new mechanistic insights into the pathogenesis of kidney diseases and potentially enable targeted dietary or pharmacological interventions.

Investigation of Functional Cytochrome P450 4A Enzymes in Liver and Kidney of Pigs, Cats, Tree Shrews, and Dogs in Comparison with the Metabolic Capacity of Human P450 4A11.

Pigs are sometimes used in preclinical drug metabolism studies, with growing interest, and thus their drug-metabolizing enzymes, including the cytochromes P450 (P450 or CYP; EC 1.14.14.1), need to be examined. In the present study, novel CYP4A cDNAs were isolated and characterized, namely, pig CYP4A23 and CYP4A90; cat CYP4A37 and CYP4A106; and tree shrew CYP4A11a, CYP4A11d, CYP4A11e, CYP4A11f, and CYP4A11g. For comparison, the following known CYP4A cDNAs were also analyzed: pig CYP4A21 and dog CYP4A37, CYP4A38, and CYP4A39. These CYP4A cDNAs all contained open reading frames of 504-513 amino acids and had high amino acid sequence identity (74%-80%) with human CYP4As. Phylogenetic analysis of amino acid sequences revealed that these CYP4As were clustered in each species. All CYP4A genes contained 12 coding exons and formed a gene cluster in the corresponding genomic regions. A range of tissue types were analyzed, and these CYP4A mRNAs were preferentially expressed in liver and/or kidney, except for pig CYP4A90, which showed preferential expression in lung and duodenum. CYP4A enzymes, heterologously expressed in Escherichia coli, preferentially catalyzed lauric acid 12-hydroxylation and arachidonic acid 20-hydroxylation, just as human CYP4A11 does, with the same regioselectivity (i.e., at the ω-position of fatty acids). These results imply that dog, cat, pig, and tree shrew CYP4As have functional characteristics similar to those of human CYP4A11, with minor differences in lauric acid 12-hydroxylation. SIGNIFICANCE STATEMENT: Cytochrome P450 (P450, CYP) 4As are important P450s in human biological processes because of their fatty acid-metabolizing ability. Pig CYP4A21, CYP4A23, and CYP4A90; cat CYP4A37 and CYP4A106; tree shrew CYP4A11a, CYP4A11d, CYP4A11e, CYP4A11f, and CYP4A11g; and dog CYP4A37, CYP4A38, and CYP4A39 cDNAs were isolated and analyzed. These CYP4A cDNAs shared relatively high sequence identities with human CYP4A11 and CYP4A22. Pig, cat, tree shrew, and dog CYP4As in the liver and kidneys are likely to catalyze the ω-hydroxylation of fatty acids.

Hepatozoon Canis in Labrador Dog with Azotaemia and its Therapeutic Management

A 10-year-old female Labrador dog weighing around 30 kg was presented at Department of Teaching Veterinary Clinical Complex, Mumbai Veterinary College, Parel, Mumbai (Maharashtra). Previous history of oral medications of doxycycline that leads to vomition, recent tooth eruption which leads to anorexia, dull in appearance, lethargic. Clinical examination revealed pyrexia (103°F), pale mucous membrane, dehydration (+), azotemic. Upon blood reports revels low haemoglobin and platelet count and high kidney and liver enzyme values. The dogs were treated with inj. Imidocarb dipropionate @5 mg/ kg B.W. twice in month and inj. Metronidazole @ 20mg/kg B.W. for 10 days along with haematinics, liver tonics and antacids. Dogs showed complete recovery after 8 days of therapy.

Dietary glycine supplementation enhances syntheses of creatine and glutathione by tissues of hybrid striped bass (Morone saxatilis ♀ × Morone chrysops ♂) fed soybean meal-based diets

BackgroundWe recently reported that supplementing glycine to soybean meal-based diets is necessary for the optimum growth of 5- to 40-g (Phase-I) and 110- to 240-g (Phase-II) hybrid striped bass (HSB), as well as their intestinal health. Although glycine serves as an essential substrate for syntheses of creatine and glutathione (GSH) in mammals (e.g., pigs), little is known about these metabolic pathways or their nutritional regulation in fish. This study tested the hypothesis that glycine supplementation enhances the activities of creatine- and GSH-forming enzymes as well as creatine and GSH availabilities in tissues of hybrid striped bass (HSB; Morone saxatilis♀ × Morone chrysops♂).MethodsPhase-I and Phase-II HSB were fed a soybean meal-based diet supplemented with 0%, 1%, or 2% glycine for 8 weeks. At the end of the 56-d feeding, tissues (liver, intestine, skeletal muscle, kidneys, and pancreas) were collected for biochemical analyses.ResultsIn contrast to terrestrial mammals and birds, creatine synthesis occurred primarily in skeletal muscle from all HSB. The liver was most active in GSH synthesis among the HSB tissues studied. In Phase-I HSB, supplementation with 1% or 2% glycine increased (P < 0.05) concentrations of intramuscular creatine (15%–19%) and hepatic GSH (8%–11%), while reducing (P < 0.05) hepatic GSH sulfide (GSSG)/GSH ratios by 14%–15%, compared with the 0-glycine group; there were no differences (P > 0.05) in these variables between the 1% and 2% glycine groups. In Phase-II HSB, supplementation with 1% and 2% glycine increased (P < 0.05) concentrations of creatine and GSH in the muscle (15%–27%) and liver (11%–20%) in a dose-dependent manner, with reduced ratios of hepatic GSSG/GSH in the 1% or 2% glycine group. In all HSB, supplementation with 1% and 2% glycine dose-dependently increased (P < 0.05) activities of intramuscular arginine:glycine amidinotransferase (22%–41%) and hepatic γ-glutamylcysteine synthetase (17%–37%), with elevated activities of intramuscular guanidinoacetate methyltransferase and hepatic GSH synthetase and GSH reductase in the 1% or 2% glycine group. Glycine supplementation also increased (P < 0.05) concentrations of creatine and activities of its synthetic enzymes in tail kidneys and pancreas, and concentrations of GSH and activities of its synthetic enzymes in the proximal intestine.ConclusionsSkeletal muscle and liver are the major organs for creatine and GSH syntheses in HSB, respectively. Dietary glycine intake regulates creatine and GSH syntheses by both Phase-I and Phase-II HSB in a tissue-specific manner. Based on the metabolic data, glycine is a conditionally essential amino acid for the growing fish.

Ameliorative effect of licorice extract against the detrimental effect of glyphosate-based pesticide: Toxicity and health

This study sheds the light on the potential of licorice (Glycyrrhiza glabra) root aqueous extract as a cornerstone for mitigating and detoxifying the residues of the widely used agricultural Glyphosate-based pesticides (GBPs). This study examined the GBPs toxic effects on kidney, liver, thyroid functions, and apoptosis using 50 adult male albino rats. All rats were divided into 5 groups, with 10 each. Control: served as untreated rats. GBP: rats were treated with 1 mL glyphosate solution 24 % orally for three weeks. The glyphosate-treated rats were gavaged with licorice root aqueous extractsolution (100, 200, and 300 mg/mLdistilled water, respectively) daily for three weeks. Licorice root aqueous extract solution (300 mg/mL distilled water) yielded notable reductions in liver, kidney enzymes, albumin, and AFP levels within the serum. Immunological tests, including immunohistochemical evaluations of caspase-3 and TNF-α expressions revealed a dose-dependent attenuation of apoptosis and inflammation with licorice intervention. This will provide a valuable perspective for agricultural practices future and paving the way for a more sustainable approach for using GBPs in animal agriculture industries.

Using &lt;i&gt;Origanum vulgare&lt;/i&gt; L. in the floor management of chickens as an element of organic poultry farming

The article provides the results of the use of dried Origanum vulgare mass as an additional component of bedding material in chickens of the Hubbard Redbro M meat-and-egg cross. Origanum vulgare dried mass was added at the rate of 0.5 kg per experimental group daily from the age of 45 days after the transfer of chickens to floor management. The number of heads for each group was 35. The live weight advantage at the age of 2 months of the experimental group of chickens over the control group is 102.5 g, at 75 days of age is 216.5 g, at 90 days of age is 326.0 g and at the age of 105 days is 403.0 g. The SBA increased at the background of the S. aureus test culture: there was a significant suppression of colonies in the first five hours of exposure, and at the background of the E. coli test culture there was a suppression throughout the entire study period. The intensification of metabolic processes was noted in chickens of the experimental group, due to increased protein metabolism, liver and kidney enzymes of blood serum, which was also associated with an increased concentration of thyroid hormones. All these factors made it possible to raise significantly the gain in live weight by an average of 0.11 kg, which increased the slaughter weight by 8.4 %. Almost all indicators of the development of internal organs in chickens of group II are within significant limits of the difference compared with the control group.

Preclinical safety evaluation of the ethanolic extract from campomanesia guazumifolia (cambess.) O. Berg fruits peels in rats

The toxicological potential of the ethanolic extract from Campomanesia guazumifolia (EECG), a species traditionally recognised for its antidiabetic, anti-inflammatory and hypercholesterolemic properties, was investigated in acute and subacute toxicity models in rats. In the acute toxicity test, 2000 mg/kg of EECG was administered orally in female rats, while male and female rats received 250, 500 or 750 mg/kg of EECG for the subacute toxicity test. No evidence of toxicity was observed in the animals acutely exposed, indicating that the LD50 is above 2000 mg/kg. However, repeated exposure to this extract resulted in alterations in important biochemical parameters indicative of hepatic and renal toxicity, including AST, ALT, creatinine, urea, and cholesterol. Additionally, some hematological parameters were also changed by the treatment. EECG demonstrated low toxicological potential. Nevertheless, given the observed changes in liver and kidney enzymes, further investigations into the protective effects of this extract following repeated administration are warranted.

Kidney and Liver Predictors of Adults Hospitalized with COVID-19 Infection

SARS-CoV-2 damages not only the lungs, but also the liver and kidney. Most critically ill COVID-19 patients have liver and kidney dysfunctions. The early identification of patients with COVID-19 who will develop severe or critical disease symptoms is important for delivering proper and early treatment. This research studies the correlation of liver and kidney function indexes and COVID-19 outcomes. Electronic medical record data from 391 patients diagnosed with COVID-19 in the COVID-19 Department, Galilee Medical Center, Nahariya, Israel were collected. Epidemiological, clinical, laboratory, and imaging variables were analyzed. The liver and kidney enzyme indexes were measured upon admission and discharge. A correlation between laboratory levels and severity and mortality of COVID-19 patients was undertaken. This study included 391 COVID-19 patients, 258 mild patients and 133 severe patients. Multivariate stepwise regression analyses and discriminant analyses were used to identify and validate powerful predictors. The main outcome was death or invasive ventilation. Three factors, namely higher urea nitrogen (BUN) and IL-6, and lower albumin levels, were the most powerful predictors of mortality, and classified the results (survival vs. death) correctly in 85% of cases (diagnostic accuracy) with a sensitivity of 88% and a specificity 55%. Compared with mild patients, severe patients had lower albumin (ALB), higher alanine aminotransferase (ALT), aspartate aminotransferase (AST) and BUN (all p &lt; 0.001). COVID-19 patients, especially severe patients, have damage to liver and kidney function. BUN, IL-6 and albumin are factors predicting mortality while fibrinogen and AST could be independent factors for predicting the severity of COVID-19.

Evaluation of hematological and blood biochemical indices in cultured Nile tilapia (Oreochromis niloticus) as affected by using phage therapy against Pseudomonas aeruginosa

Abstract Pseudomonas spp. causes significant losses in aquaculture, consecutive use of antibiotics, and reveals bacterial resistance; therefore, therapeutic bacteriophages, commonly called phages, are a promising potential alternative to antibiotics in the management of bacterial infections of a wide range of organisms, including cultured fish. The novelty of current work is represented in examining the lytic activity of four phages and their combination compared to the antibiotic streptomycin on Pseudomonas aeruginosa-infected Nile tilapia (Oreochromis niloticus) while measuring the hematological and blood biochemical parameters as a response for phage therapy. This study evaluated the in vitro killing curve for each phage using a growth curve that measured the OD600 after a single phage suspension was combined with the host P. aeruginosa, considered the best multiplicity of infection (MOI) for each phage. A144 healthy fish were acclimatized in the laboratory and divided into six groups: control, P. aeruginosa-infected fish, streptomycin, phage Ps1, Ps2, both (Ps1 and Ps2), were added to the T3, T4, T5, and T6 groups, respectively. Our findings demonstrated that P. aeruginosa infection caused surface body hemorrhages, tail and fin rot, irritated skin, superficial ulcers, and 100% mortality through 14 days. P. aeruginosa caused a reduction in hemoglobin (Hb), red blood cells (RBCs), platelet number (PLt), and platelet crit (PCT) count, protein, albumin, and A/G ratio; however, an increase in hematocrit (Hct), red cell distribution width (RDW), PDW, MPV compared to other groups after three days of infection and the effects increased after 12 days post-infection. The fish vaccinated with P1 (T4) and P1+P2 (T6) showed enhanced levels of Hb, RBCs, PLt, PCt, protein, albumin and decreased levels of RDW, PDW, MPV, and liver and kidney enzymes with enhanced contents more than streptomycin and closer to the control group. The biochemical markers recorded significant changes indicating liver and kidney impairments due to the infection with P. aeruginosa. It can be concluded that P1 and P1+P2 combinations could be used as therapy in Pseudomonas-infected fish to enhance their blood parameters and performance.

Potential Activity of Micafungin and Amphotericin B Co-Encapsulated in Nanoemulsion against Systemic Candida auris Infection in a Mice Model.

The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by C. auris. NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij® 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with Candida auris CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by C. auris can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.

Triterpenes G-A and G-E from Galphimia glauca with anti-inflammatory and anti-arthritic activity in mice

Ethnopharmacological relevanceGalphimia glauca is a medicinal plant that treats inflammatory and anti-rheumatic problems. Its anti-inflammatory capacity has been reported pharmacologically, attributed to the triterpenes G-A and G-E. AimThe objective of the present work was to measure the anti-inflammatory and immunomodulatory effect of the methanolic extract (GgMeOH) of Galphimia glauca and the isolated galphimines G-A and G-E, first in an acute test of plantar edema with carrageenan, and later in the model of experimental-induced arthritis with CFA. The effect was measured by quantifying joint inflammation, the concentration of pro- (TNF-α, IL-6, IL-17) and anti-inflammatory (IL-10, and IL-4) cytokines, and the ADA enzyme in joints, kidneys, and spleen from mice with experimental arthritis. MethodThe extract and the active triterpenes were obtained according to established methods using different chromatographic techniques. Female ICR strain mice were subjected to intraplantar administration with carrageenan and treated with different doses of GgMeOH, G-A, and G-E; edema was monitored at different times. Subsequently, the concentration of TNF-a and IL-10 in the spleen and swollen paw was quantified. Meloxicam (MEL) was used as an anti-inflammatory control drug. The most effective doses of each treatment were analyzed using a complete Freunds adjuvant (CFA)-induced experimental arthritis model. Joint inflammation was followed throughout the experiment. Ultimately, the concentration of inflammation markers, oxidant stress, and ADA activity was quantified. In this experimental stage, methotrexate (MTX) was used as an antiarthritic drug. ResultsTreatments derived from G. glauca, GgMeOH (DE50 = 158 mg/kg), G-A (DE50 = 2 mg/kg), and G-E (DE50 = 1.5 mg/kg) caused an anti-inflammatory effect in the plantar edema test with carrageenan. In the CFA model, joint inflammation decreased with all natural treatments; GgMeOH and G-A inhibited the ADA enzyme in all organs analyzed (joints, serum, spleen, left and right kidneys), while G-E inhibited the enzyme in joints, serum, and left kidney. CFA caused an increase in the weight index of the organs, an effect that was counteracted by the administration of G. glauca treatments, which also modulate the response to the cytokines analyzed in the different organs (IL-4, IL-10, IL-17, IL-6, and TNF- α). ConclusionIt is shown, for the first time, that the GgMeOH extract and the triterpenes G-A and G-E of Galphimia glauca have an anti-arthritic effect (anti-inflammatory, immunomodulatory, antioxidant, and ADA inhibitor), using an experimental arthritis model with CFA. Therefore, knowledge of the plant as a possible therapeutic agent for this rheumatic condition is expanding.

B-esterases activities in several tissues of the marine fish: sea bass and hake, as potential biomarkers of bisphenol A derivatives

In the marine environment, a new threat linked to plastic pollution relates to plastic additives. This threat encompasses multiple chemical compound groups with a high bioaccumulation potential for these chemical mixtures. Hence, informative biomarkers are needed to indicate the effects of environmentally realistic mixtures of these additives. This study proposes an in vitro approach using tissue homogenates of two marine fish, the European sea bass and hake, which are both of interest in aquaculture and fisheries. The selected biomarkers are B-esterase activities comprising acetylcholinesterase (AChE) and carboxylesterases (CEs). The physiological role of AChE in brain and muscle is mainly neural transmission, while CEs participate in liver detoxification processes. However, B-esterases are also widely distributed in other tissues/organs, where their role is yet to be determined, but their inhibition may have undesired biological consequences. Here, we compared the interaction of the plastic additives, bisphenol A and some of its derivatives, like tetrabromobisphenol A (TBBPA), with B-esterase activities. We particularly focused not only on the robust and broadly distributed CE enzymes in brain, gonad, liver, kidney, and plasma tissues of two marine fish, but also on the use of two commercial substrates, p-nitrophenyl butyrate and α-naphthyl butyrate, tentatively representing two CE isoforms. The results evidenced specific species and tissue responses that could be due to a diverse isoform composition. They identified sea bass as better protected against neurotoxic exposures, at least in terms of B-esterase composition. The flame retardant TBBPA was the most reactive to B-esterases inhibition, although Bisphenol A bis (2,3-dihydroxy propyl) ether and Bisphenol F bis (3-chloro-2-hydroxypropyl) ether warrant further toxicology assessments.

The impact of some metals, molecular docking and molecular dynamic calculations on glucose 6-phosphate dehydrogenase activity in Capoeta trutta (Heckel, 1843) tissue

The first enzyme of the pentose phosphate metabolic pathway is glucose 6-phosphate dehydrogenase (d-glucose-6-phosphate: NADP + oxidoreductase EC1.1.1.49; G6PD). G6PD has essential functions such as membrane lipid synthesis, ribose 5-phosphate, and NADPH production. In this study, the G6PD enzyme was purified from kidney, liver, and gill tissues of Capoeta trutta, one of the dominant fish species in the Euphrates-Tigris River System, and the in vitro effects of some metals (Ag+, Cd2+, Cu2+, Fe2+, Ni2+, Pb2+ and Zn2+) on the enzyme activity were investigated. For this purpose, firstly, the G6PD enzyme was purified from tissues using a 2′, 5′-ADP Sepharose 4B affinity column. The purity of the enzyme was checked by the SDS-PAGE method and a single band was seen in the gel. After the purity of the enzyme was determined, the effects of metals on the enzyme activity were determined using the spectrophotometric method. As a result of the study, it was determined that the Ag+ ion was the most potent inhibitor for C. trutta gill, kidney, and liver G6PD enzymes. Lastly, calculations were made to examine the activity of the glucose 6-phosphate dehydrogenase molecule against the G6PD enzymes. Afterwards, the interaction of the glucose 6-phosphate dehydrogenase molecule with the protein (PDB ID: 5JYU and 2BH9) with the highest activity was calculated in the range of 0–100 ns. Finally, ADME/T calculation was made to predict the effects and reactions of glucose 6-phosphate dehydrogenase molecule in human metabolism. This study explores the physiological functions and environmental sensitivities of G6PD in a dominant fish species, while also investigating its potential interactions and metabolic roles in humans. Understanding these aspects can contribute to environmental monitoring, fish health management, and even pharmaceutical development.

Ifanosine: Olea europaea L. and Hyphaene thebaica L. combination, from traditional utilization to rational formulation: Preclinical and clinical efficacy on hypertensives patients

Ethnopharmacological relevanceOlea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine). Aim of the studyThe primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine. Materials and methodsIn vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days. ResultsAqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects. ConclusionThis study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies.

Renal and Hepatic Toxicity of Alpha-Cypermethrine Pesticide Used on Agricultural Farmers Living Closed to Tigris river, Iraq

The study was conducted from October 15, 2021, to February 15, 2022, in Wasit Governorate, Iraq, targeting farmers of different ages exposed to chemical pesticides along the banks of the Tigris River within the administrative borders of the province. The objective of the study was to identify the impact of alpha-cypermethrin on the health condition of farmers during spraying operations. This was achieved by measuring and identifying changes in vital indicators through biochemical tests, specifically kidney functions and liver enzymes. A total of 200 samples were collected for the study and divided into two groups. The first group comprised 150 samples from farmers exposed to the pesticide, categorized into two age groups. The first subgroup included individuals older than 18 (100 samples), and the second included those under 18 (50 samples). The second group, serving as the control, consisted of 50 samples, with 25 individuals over 18 and 25 under 18. Results revealed high significant differences (P≤0.01) in the concentrations of kidney functions (urea and creatinine) and hepatic enzymes (AST, ALT, and ALP) among individuals exposed to the pesticide compared to the concentrations in the non-exposed control group. The study's findings lead to the conclusion that direct exposure to alpha-cypermethrin showed an impact on overall body functions and affected biomarkers, particularly kidney and liver enzyme functions. Moreover, the adverse effects were more pronounced in older farmers exposed to the pesticide than their younger counterparts.

Acidente ofídico em equinos no Bioma Amazônico, Pará, Brasil

ABSTRACT: Bothrops atrox is the most common viper in the Amazon, and its venom causes local and systemic changes. This report describes the clinicopathological and laboratory findings of ophidism due to Bothrops in six horses in Pará, Brazil. The animals, which belonged to five different rural properties, showed clinical signs of apathy, anorexia, and increased touch sensitivity in areas of increased volume. Three animals were bitten in the distal part of the pelvic limbs and three in the head area. The affected animals in the distal limb area exhibited marked edema extending from the fetlock to the thigh and had difficulty moving. Those affected in the head region exhibited an increase in volume that gave the appearance of a “rhinoceros head,” as well as blackening of the mucosa of the lips and gums. All animals exhibited tachycardia and tachypnea, and laboratory findings of two animals showed anemia, leukocytosis, increased clotting time, and elevated liver (AST and GGT) and kidney enzymes (urea and creatinine). Treatment was ineffective, and three of four treated animals died. Necropsy was performed on three animals, revealing extensive hemorrhage in the tissues at the snake bite sites and incoagulable bloody fluid in the cavities. Congestion was observed in the diaphragm, in the serosa of the small intestine, and in lighter areas on the renal surface. Histopathology showed muscle degeneration, necrosis, acute tubular necrosis, hemorrhage, and hyaline casts in the kidneys. This case report highlights the clinicopathological findings of snakebite in horses. In addition, this seems to be the first report of bothropic envenom in a mule in Brazil.

Effect of Fipronil Exposure on Hematological Aspects of Rhesus Monkeys (Macaca mulatta): Risk and Toxicity Assessment in Agro-Workers.

Fipronil (FPN) is a broad-spectrum phenylpyrazole insecticide, widely used in agriculture and veterinary medicine. Published research on FPN toxicity has established the fact that its inhalation or dermal exposure may lead to very serious clinical outcomes in non-target animals. In line to its exposure and toxicity related damage, FPN has been investigated in many invertebrates, however, its exposure-related noxiousness is less reported in higher animals. To assess the FPN-induced effects to agro-workers in the field, in the present study, we used physiological human surrogates, adult rhesus monkeys as models. We exposed well habituated, chair restraint adult rhesus monkeys with a field spray concentration of FPN (0.3 mg/1 mL distilled water) through an inhalation route in the closed system. Animals were divided into control and treatment groups, each containing three animals. Inflammatory and hematological effects were determined by evaluating the kidney and liver biomarker enzymes; serum creatinine and alanine transaminase (ALT), aspartate transaminase (AST) levels respectively. Our findings reveal that FPN treated monkeys show significantly increased levels of ALT (p = 0.000461), AST (p = 0.0681) and creatinine (p = 0.00656) as compared to the control group. Furthermore, significant differences of red blood cells (RBCs) (p = 0.0139) and white blood cells (WBCs) (p = 0.00642) were also observed in the treated and control group monkeys which reflect strong toxic effects on the blood cells. Our findings demonstrate that FPN exposure is very toxic to higher animals and causes severe damage to the liver and kidneys along with other clinical problems. The study highlights the effect and impact of passive inhalation of insecticides in intentionally carefree agro-workers and raises the concern of public awareness toward pesticides use.