Enzymes In Rats Research Articles

Renal denervation ameliorated salt-induced hypertension by improving cardiac work, cardiac enzyme and oxidative balance in Sprague-Dawley rats

BackgroundHypertension is associated with cardiovascular dysfunction, dysregulation of the antioxidant system and alteration of the level of some enzymes in the metabolic pathway. The possible modulatory effect of acute renal denervation (ARD) on cardiovascular function and the antioxidant system is still a subject of intense debate. This study sought to ascertain the ameliorative effects of ARD on cardiovascular parameters, antioxidant system, creatine kinase and lactate dehydrogenase levels. MethodsThirty-six Sprague-Dawley rats (5–6 weeks old) were divided into 6 groups of 6 animals each consisting of Normal Salt, High Salt, Normal Salt + Sham Denervation, High Salt + Sham Denervation, Normal Salt + Renal Denervation and High Salt + Renal Denervation. Induction of hypertension with 8 % salt in the diet lasted for 8 weeks. Renal or Sham denervation was thereafter done on selected groups. At the end of the experimental period, cardiovascular parameters, plasma antioxidant status, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) levels were assessed. Significance level was set at p < 0.05. ResultsSalt-loading significantly increased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), rate pressure product (RPP) while reducing superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT). Acute renal denervation significantly (p < 0.0001) reduced SBP, DBP, MABP, RPP, LDH and norepinephrine level while increasing SOD, GSH and CAT. ARD did not significantly alter CK level. ConclusionAcute renal denervation, by reducing sympathetic activity, ameliorates cardiovascular and antioxidant functions as well as reduces LDH level without significantly altering CK level in salt-induced hypertension.

Assessing the Impact of Annona muricata Aqueous Extract on Liver Enzymes in Wister Rats Exposed to Paracetamol Over Dose

Aims: This study examines the effect of the aqueous leaf extract of Annona Muricata on liver enzymes in wister rats using the spectrophotometric method. Methodology: 20 Wister rats were divided into groups A, B, C, and D, of 5 rats each, housed, fed, and the experimental groups administered treatments orally in distilled water (10 ml/kg) by means of orogastric cannula for 14 days. 500g of the plant powder was submerged for 72 hours 1500ml of distilled water. The sample was taken with a rotating evaporator, an electrical evaporator extraction apparatus. With water heated to 45°C, the solvent was removed. Before use, a paste-like sample was made and kept in a refrigerator at 4 degrees Celsius. The animals in group A were used as the control. The animals in group B were given feeds + 20mg of paracetamol, and the animals in group C were administered 100mg of paracetamol + silymarin. In comparison, the ones in group D were given 150mg of paracetamol + Annona muricata extracts. The animals were then sacrificed 48 hours following the final dose. A blood sample was collected, allowed to coagulate, and then the serum was separated, while the liver was excised and utilized for biochemical analyses. Results: The alanine aminotransferase activities (ul) recorded 9.0±2.71, 14.67±1.5, 13.50±0.58, 15.75±2.50 for animals in groups A, B, C, and D respectively with corresponding activities of aspartate aminotransferase (ul) of 7.25±0.50, 27.33±4.04, 20.00±2.71, 17.25±1.71. Results revealed a significant difference (p&lt;0.05) in the activities of ALT and AST of all the treated groups. Thus, the aqueous leaf extract of Annona muricata could be hepato-protective. The silymarin could also be hepatoprotective, but it is less effective than Annona muricata. The untreated group, B, showed elevated levels of alanine aminotransferase and aspartate aminotransferase, confirming paracetamol's hepatotoxic activity. Conclusion: The ethanol leaf extract of Annona muricata decreased the activities of liver enzymes in male wister rats, suggesting its hepato-protective tendency. It also does not encourage body weight loss.

Synergistic Effect of Naringin and Glimepiride in Streptozotocin-induced Diabetic Rats.

Evaluation of the synergistic effect of Naringin and Glimepiride in streptozotocin (STZ)-induced diabetic rats. Wistar rats were chosen and divided into five groups (n=6). STZ was used for the induction of diabetes. The combination of naringin and glimepiride was administered to diabetic rats. The changes in fasting blood sugar, body weight, Hb, HbA1c, and creatinine were evaluated, and urine was collected and the volume was observed. The lipid profiles like TC, HDL, LDL, and TG were measured. The biochemical parameters SGOT, SGPT, and ALP were analysed. Besides, endogenous antioxidant parameters like SOD, GSH, and catalase were also assessed. Lastly, the histopathological study of the beta cells in islets of the pancreas, glomerulus, and tubules of kidney and liver cells was conducted in all groups. The result shows significant reduction (p<0.001) of blood sugar in the naringin and glimepiride-treated group when compared with the control group (diabetes). Additionally, the combination of Naringin (100 mg/kg) and Glimepiride (0.1 mg/kg) significantly restores the creatinine levels and urine volumes, SGOT, SGPT, and ALP when compared to a single dose of administration. Further, the abnormal lipid profile levels (TC, LDL, TG, and HDL), and endogenous antioxidant enzymes (SOD, GSH, catalase) in diabetic control rats were restored to normal levels in a significant manner. The histopathological result reveals significant alterations, including hypertrophy of islets and mild degeneration, renal necrosis, and inflammation of hepatocytes. A synergistic effect of Naringin and glimepiride was observed during the estimation of various biochemical parameters like body weight, fasting blood sugar, creatinine, urine level, TG, total cholesterol, SGOT, SGPT, ALP, Insulin, HbA1c, antioxidant parameters like SOD, GSH, and catalase in STZ-induced diabetic rats. Further, the combination of therapy improves the protective effect of the pancreas, kidney, and liver, suggesting a potential antidiabetic effect.

Virgin coconut oil mitigates the hepatotoxic effect of atrazine and diabetes on liver enzymes in male Wistar rats

To assess the hepatoprotective action of Virgin Coconut Oil(VCO) in atrazine administered rats. Adult male Wistar rats weighing 180-200 g body weight were separated into two major experimental groups. 35 rats in the test group were divided into five sub-groups of 7rats: Subgroup (SG)1,2 and 3 received 10 ml/kg body weight of distilled water, 10 ml/kg VCO and 123 mg/kg Atrazine (ATZ) respectively, SG 4 was diabetic control group and SG 5 was diabetic group treated with 10 ml/kg of VCO for 2weeks, after which the animals were sacrificed and blood collected for analysis. 35 rats for the recovery group were also divided into 5 subgroups of 7 rats; SG1 and 2 received 10 ml/kg body weight of distilled water and 10 ml/kg of VCO, SG 3, 4 and 5 received 123 mg/kg of ATZ for 2 weeks. After the first 2 weeks, SG 1,2,3 continued the initial treatment while the rats in SG4 and SG5 were fed with 10 ml/kg of VCO and10 ml/kg of distilled water respectively. After 2 weeks, all the animals were sacrificed and blood collected for analysis. We observed a significant increase in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of the diabetes control and diabetes treated with VCO groups compared to the normal control. In the groups administered with atrazine, the result showed elevations in serum AST and ALT. With VCO,a significant decrease in ALT levels when compared to the ATZ continued group was observed, further potentiating the hepatoprotective ability of VCO.

Use of human Caco-2 cells and HPAE-PAD for α-glucosidase assay

To measure α-glucosidase activity, rat intestinal acetone powder is commonly used as a source of α-glucosidase, and the mutarotase-glucose oxidase (GOD) methods commonly used to quantitate glucose produced by enzymatic hydrolysis of the substrates. In this study, we compared human Caco-2 cell extracts with rat intestinal acetone powder extracts. We also compared high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) with the mutarotase-GOD method. The sensitivity of HPAE-PAD was higher than that of mutarotase-GOD. The glucose concentration quantified by HPAE-PAD was similar to that quantified using the mutarotase-GOD method. In the maltase reaction, 1-deoxynojirimycin (1-DNJ) exerted a more potent inhibitory effect on human enzymes than on rat enzymes. This order was reversed during the sucrase reaction. These results suggested that the combined use of Caco-2 cell extracts and HPAE-PAD is advantageous for use in α-glucosidase-related basic research.

Effects of nicotine on microRNA-124 expression in bile duct ligation-induced liver fibrosis in rats

BackgroundNicotine, the main compound of smoking may exert its effects by changing the expression of microRNAs (miRNAs). This study was conducted to further investigate the molecular mechanisms of miRNA-dependent effects of nicotine in an animal model of liver fibrosis.MethodsThe bile duct ligation (BDL) approach was used to create a model of liver fibrosis. Twenty-four male Wistar rats were used in the study. The effects of nicotine administration on miRNA-124 expression, as well as alpha-smooth muscle actin (liver fibrosis marker) and chemokine ligand 2 (an inflammatory chemokine), were investigated using RT-qPCR. In addition, the mRNA and protein expression of signal transducer and activator of transcription 3 (STAT-3; as a potential target for miRNA-124) were investigated by RT-qPCR and immunofluorescence, respectively. Liver enzyme activity levels were measured using a colorimetric assay. In addition, the effects of nicotine on the process of liver fibrosis were investigated with histological studies.ResultsThe development of liver fibrosis in BDL rats and nicotine administration led to a decrease in miRNA-124 expression. The decrease in the expression is accompanied by the increase in the expression of fibrotic and proinflammatory genes. Also, an increase in STAT-3 mRNA and protein expression was observed in the fibrotic rats that received nicotine. In addition, the significant increase in bilirubin and liver enzymes in fibrotic rats worsens with nicotine administration. The results of histological studies also confirm these results.ConclusionConsidering that miRNA-124 is an anti-inflammatory miRNA, it can be concluded that the decrease in its expression due to nicotine exposure leads to an increase in inflammatory processes and subsequently to an increase in liver fibrosis.

Ameliorative potential of β-sitosterol and lupeol on high fat diet and streptozotocin -induced hepatorenal and cardiac complications via regulation of carbohydrate metabolic enzymes in diabetic rats

Introductionβ-Sitosterol is a plant-derived compound that shares structural similarities with cholesterol and is used to treat coronary artery disease, prostate cancer, breast cancer, and hypercholesterolemia etc. Lupeol is a natural pentacyclic triterpene, found in a variety of fruits, vegetables, and traditional Chinese medicines like Astragalusmembranaceus and AtractylodesmacrocephalaKoidz. Numerous pharmacological activities of lupeol have been investigated; they include applications as antioxidant, antiviral, antihypertensive, anti-inflammatory and antitumor agents.The current study wasaimed to examine the potential benefits of β-sitosterol and lupeol in reducing pathophysiological complications caused by high fat diet and streptozotocin by regulating the enzymes involved in the metabolism of carbohydrates in diabetic rats as there was no study on this aspect. MethodsMale albino wistar rats were given a high-fat diet for two weeks in order to cause diabetes in them. Following a two-week period, the animals were administered a low dosage of streptozotocin and maintained on an overnight fast. Using commercial diagnostic kits, we assessed plasma glucose and glycated hemoglobin (HbA1C). Plasma insulin level was assayed with the help of an ELISA kit and other assays were made biochemically. ResultsThe homeostatic model of insulin resistance, glucose 6-phosphatase, fructose 1,6-bisphosphatase, and blood glucose levels all significantly increased in the diabetic rats, while plasma insulin, hexokinase, glucose 6-phosphate dehydrogenase, and glycogen content significantly decreased.In addition, the hepatic (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and renal (urea and creatinine) indicators in diabetic rats were raised, and their lipid profiles were disrupted. However, diabetic rats treated with lupeol and β-sitosterol significantly restored all these changed parameters to the levels close to normal. Furthermore, the treatment of lupeol and β sitosterol improved the liver, kidney and heart histology alteration to near normal and prevented the body weight loss. DiscussionBecause of its structural polymorphism, β-sitosterol appeared to be more effective than lupeol in all the parameters investigated and thus these results imply that β sitosterol is a more effective antidiabetic medication than lupeol.

Methoxsalen Inhibits the Acquisition of Nicotine Self-Administration: Attenuation by Cotinine Replacement in Male Rats.

Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Previous studies showed that cotinine-supported self-administration in rats and rats with a history of cotinine self-administration exhibited relapse-like drug-seeking behavior, suggesting that cotinine may also be reinforcing. To date, whether cotinine may contribute to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1/2 enzymes in rats and methoxsalen is a potent CYP2B1/2 inhibitor. The study examined nicotine metabolism, self-administration, and locomotor activity. The hypothesis is that methoxsalen inhibits nicotine self-administration and cotinine replacement attenuates the inhibitory effects of methoxsalen in male rats. Methoxsalen decreased plasma cotinine levels following a subcutaneous nicotine injection. Repeated daily methoxsalen treatments reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, lower nicotine intake, and lower plasma cotinine levels. However, methoxsalen did not alter the maintenance of nicotine self-administration despite a significant reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. These results indicate that methoxsalen inhibition of cotinine formation impaired the acquisition of nicotine self-administration, and cotinine replacement attenuated the inhibitory effects of methoxsalen on the acquisition of self-administration, suggesting that cotinine may contribute to the initial development of nicotine reinforcement. Smoking cessation medications targeting nicotine's effects are only moderately effective, making it imperative to better understand the mechanisms of nicotine misuse. Methoxsalen inhibited nicotine metabolism to cotinine and impaired the acquisition of nicotine self-administration. Cotinine replacement restored plasma cotinine and attenuated the methoxsalen inhibition of nicotine self-administration in rats. These results suggest that (1) the inhibition of nicotine metabolism may be a viable strategy in reducing the development of nicotine reinforcement, (2) methoxsalen may be translationally valuable, and (3) cotinine may be a potential pharmacological target for therapeutic development given its important role in the initial development of nicotine reinforcement.

Effects of leonardite and succimer treatment on enzyme activity in rats exposed to lead acetate

The study aimed to research in vivo changes in the enzyme activity of the blood and liver of laboratory rats under continuous exposition to a moderate dose of lead acetate while receiving succimer together with humic feed additive madden out of leonardite. Two-month-old white rats were used to assess the detoxifying properties of the humic compounds leonardite and lignite. To conduct the study, a total of 32 male laboratory rats were divided into four groups, each consisting of eight animals, using the analog pair approach. Rats received a pre-meal injection of lead acetate at a dose of 7 mg/100 g of animal weight (1/110 LD50) using a veterinary feeding needle. Humic feed additives were supplied to animals by creating solutions from leonardite at a dosage of 18 mg/kg depending on the active ingredient. Succimer was prescribed in an amount of 30 mg/kg, previously dissolved in apple juice using a feeding tube 3 hours after eating one time in a day. Upon analyzing the collected data, it can be deduced that the treatment involving succimer and the humic-based feed additive leonardite alongside lead acetate poisoning yielded improved protein metabolism and activity of enzymes in poisoned rats. Notably, in all statistically significant instances (P &lt; 0.05) of improvement in indicators among animals in that research group, the numerical values closely approximated those of intact animals. The key distinction between treating animals with succimer alone and the combination of succimer and leonardite primarily manifested in alterations in the activity of liver enzymes involved in the antioxidant system such as: catalase, superoxide dismutase, glutathione peroxidase.

Effect of oral dosage of Spirulina platensis and silver nanoparticles on glucose, lipid profile, and liver enzymes in male rats induced di-abetics by alloxan

Diabetes is believed to be one of the most important challenges that are facing societies around the world. The research was conducted to determine the effectiveness of 150 mg/ml of Spirulina platensis and 10 mg/ml of silver nanoparticles Ag-NPs on the sugar level, lipid profile, and liver enzyme concentration in male rats. Diabetes was induced with alloxan and bred for four weeks. The rats were divided randomly into five groups and every single group contained five rats; M1 was the control group, M2 was a treated diabetic rat, M3 treated diabetic rats with 10 mg/ml Ag-NPs, M4 treated diabetic rats with 150 mg/ml S. platensis and M5 group with diabetic rats that were treated with 10 mg/ml Ag-NPs + 150 mg/ml S. platensis. The results showed that the group of rats infected with Alloxan (M2) caused negative effects at a significant level (P&lt;0.05) on the blood sugar level, while the group of rats treated with Ag-NPs (M3) or S. platensis (M4) or both (M5) showed a positive effect on the blood glucose rate, which reached 292.6, 210.5, and 199.3 mg/dl, respectively, compared to the (M2) group, which was 441.8 mg/dl. The results of the lipids profile, the group with diabetes (M2) showed an increase in the level of triglycerides (TG), cholesterol (TC), low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL), and a decrease in the level of high-density lipoproteins (HDL). The treatment groups M3, M4, and M5 improved significantly positive blood lipid levels. The same situation applied to the liver enzymes AST, ALT, and ALP, whose values decreased significantly in the treatment groups (M3, M4, and M5) compared to the infection group (M2).&#x0D;

Metabolic mechanism and pharmacological study of albendazole in secondary hepatic alveolar echinococcosis (HAE) model rats.

Albendazole (ABZ) is the primary treatment for alveolar echinococcosis (AE); however, its limited solubility impacts oral bioavailability, affecting therapeutic outcomes. In this study, various ABZ-solubilizing formulations, including albendazole crystal dispersion system (ABZ-CSD), albendazole hydrochloride-hydroxypropyl methylcellulose phthalate composite (TABZ-HCl-H), and albendazole hydroxyethyl sulfonate-hydroxypropyl methylcellulose phthalate composite (TABZ-HES-H), were developed and evaluated. Physicochemical properties as well as liver enzyme activity were analyzed and their pharmacodynamics in an anti-secondary hepatic alveolar echinococcosis (HAE) rat model were investigated. The formulations demonstrated improved solubility, exhibiting enhanced inhibitory effects on microcysts in HAE model rats compared to albendazole tablets. However, altered hepatic drug-metabolizing enzymes in HAE model rats led to increased ABZ levels and reduced ABZ-SO production, potentially elevating drug toxicity. These findings emphasize the importance of dose adjustments in patient administration, considering the impact of alveolar echinococcosis on rat hepatic drug metabolism.

Aerobic training with moderate or high doses of vitamin D improve liver enzymes, LXRα and PGC-1α levels in rats with T2DM

Dysregulation of key transcription factors involved in hepatic energy metabolism, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and liver X receptor alpha (LXRα), has been observed in T2DM. The present study aims to investigate the effects of aerobic training and vitamin D supplementation on liver enzyme levels and the levels of PGC-1α and LXRα proteins in hepatocytes, in a rat model of T2DM. The study involved 56 male Wistar rats, divided into two groups: one was non-diabetic and acted as a control group (n = 8), and the other had induced diabetes (n = 48). The diabetic rats were then split into six subgroups: two groups received high or moderate doses of vitamin D and aerobic training (D + AT + HD and D + AT + MD); two groups received high or moderate doses of vitamin D alone (D + HD and D + MD); one group underwent aerobic training with vehicle (sesame oil; D + AT + oil), and one group was a diabetic control receiving only sesame oil (oil-receiving). The D + AT + HD and D + HD groups received 10,000 IU of vitamin D, while the D + AT + MD and D + MD groups received 5000 IU of vitamin D once a week by injection. The D + AT + oil group and the sham group received sesame oil. After eight weeks of treatment, body weight, BMI, food intake, serum insulin, glucose, 25-hydroxyvitamin D, ALT, AST, and visceral fat were measured. The levels of PGC-1α and LXRα proteins in the liver was assessed by western blotting. Statistical analysis was performed using the paired t-test, one-way analysis of variance (ANOVA), and the Tukey post hoc test at a significance level of P < 0.05. Body weight, food intake, and BMI decreased significantly in the D + AT + HD, D + AT + MD, D + AT + oil, D + HD, and D + MD groups with the highest reduction being observed in body weight and BMI in the D + AT + HD group. The D + AT + HD group exhibited the lowest levels of insulin, glucose, and HOMA-IR while the D + C group exhibited the highest levels among the diabetic groups. The D + AT + HD and D + AT + MD groups had lower levels of ALT and AST enzymes compared to the other groups with no significant difference between D + AT + HD and D + AT + MD. D + AT + HD (p = 0.001), D + AT + MD (p = 0.001), D + HD (p = 0.023), D + MD (p = 0.029), and D + AT + oil (p = 0.011) upregulated LXRα compared to D + C. Among these groups, D + AT + HD exhibited a more profound upregulation of LXRα than D + AT + MD, D + AT + oil, D + HD, and D + MD (p = 0.005; p = 0.002, p = 0.001, and p = 0.001, respectively). Similarly, D + AT + HD showed a more notable upregulation of PGC-1α compared to D + AT + oil, D + HD, and D + MD (p = 0.002; p = 0.001, and p = 0.001, respectively). Pearson correlation tests showed significant and negative correlations between serum 25-hydroxyvitamin levels and both visceral fat (r = − 0.365; p = 0.005) and HOMA-IR (r = − 0.118; p = 0.009); while positive and significant correlations between the liver-to-bodyweight ratio with both ALT and AST enzymes and also between QUICKI levels with LXRα (r = 0.578; p = 0.001) and PGC-1α (r = 0.628; p = 0.001). Combined administration of aerobic training and vitamin D supplementation potentially improves liver enzymes in type-2 diabetic rats that were simultaneous with upregulating the levels of PGC-1α and LXRα proteins in hepatocytes. These improvements were more significant when combining exercise with high-dose vitamin D supplementation. This study highlights the potential of this combination therapy as a new diabetes treatment strategy.

Date (Phoenix dactylifera L. Mill) fruit enhances sexual performance via modulation of oxido-inflammatory mediators and purinergic signaling in hypertensive male rats

Introduction The present study aimed at investigating the effect of dietary supplementation of Phoenix dactylifera, an important component of aphrodisiac supplements, on sexual performance, oxido-inflammatory mediators and purinergic signaling system in hypertensive rats. Material and methods Hypertension was induced via oral administration of 40 mg/kg L-NAME. Thereafter, the sexual performance of the experimental animals was determined and the hypertensive rats with impaired sexual activities were placed on P. dactylifera-supplemented diet for 21 days, and the effects of the treatment on the overall sexual behavior, antioxidant status, oxido-inflammatory biomarkers, and enzyme activity of the purinergic system were assessed. Results Hypertensive rats showed a significant (p < 0.05) decrease in sexual performance, elevated level of oxido-inflammatory mediators, and altered purinergic enzymes activity when compared with the control. However, sub-chronic feeding with P. dactylifera-supplemented diet improved sexual performance, significantly lowered oxido-inflammatory biomarkers, and enhanced the activity of purinergic enzymes in hypertensive rats. Conclusion Findings presented in this study suggest that dietary inclusion of P. dactylifera could be useful in managing erectile dysfunction (ED) commonly observed in subjects with hypertension. Findings highlighted in this study thus provide the scientific basis supporting the folkloric use of P. dactylifera as a key ingredient in aphrodisiac supplements.

Per- and polyfluoroalkyl substances inhibit human and rat 17β-hydroxysteroid dehydrogenase 1: Quantitative structure-activity relationship and molecular docking analysis

Per- and polyfluoroalkyl (PFAS) substances are enduring industrial materials. 17β-Hydroxysteroid dehydrogenase isoform 1 (17β-HSD1) is an estrogen metabolizing enzyme, which transforms estrone into estradiol in human placenta and rat ovary. Whether PFAS inhibit 17β-HSD1 and what the structure-activity relationship (SAR) remains unexplored. We screened 18 PFAS for inhibiting human and rat 17β-HSD1 in microsomes and studied their SAR and mode of action(MOA). Of the 11 perfluorocarboxylic acids (PFCAs), C8-C14 PFCAs at a concentration of 100 μM substantially inhibited human 17β-HSD1, with order of C11 (half-maximal inhibition concentration, IC50, 8.94 μM) > C10 (10.52 μM) > C12 (14.90 μM) > C13 (30.97 μM) > C9 (43.20 μM) > C14 (44.83 μM) > C8 (73.38 μM) > others. Of the 7 per- and poly-fluorosulfonic acids (PFSAs), the potency was C8S (IC50, 14.93 μM) > C7S (80.70 μM) > C6S (177.80 μM) > others. Of the PFCAs, C8-C14 PFCAs at 100 μM markedly reduced rat 17β-HSD1 activity, with order of C11 (IC50, 9.11 μM) > C12 (14.30 μM) > C10 (18.24 μM) > C13 (25.61 μM) > C9 (67.96 μM) > C8 (204.39 μM) > others. Of the PFSAs, the potency was C8S (IC50, 37.19 μM) > C7S (49.38 μM) > others. In contrast to PFOS (C6S), the partially fluorinated compound 6:2 FTS with an equivalent number of carbon atoms demonstrated no inhibition of human and rat 17β-HSD1 activity at a concentration of 100 μM. The inhibition of human and rat enzymes by PFAS followed a V-shaped trend from C4 to C14, with a nadir at C11. Moreover, human 17β-HSD1 was more sensitive than rat enzyme. PFAS inhibited human and rat 17β-HSD1 in a mixed mode. Docking analysis revealed that they bind to the NADPH and steroid binding site of both 17β-HSD1 enzymes. The 3D quantitative SAR (3D-QSAR) showed that hydrophobic region, hydrogen bond acceptor and donor are key factors in binding to 17β-HSD1 active sites. In conclusion, PFAS exhibit inhibitory effects on human and rat 17β-HSD1 depending on factors such as carbon chain length, degree of fluorination, and the presence of carboxylic acid or sulfonic acid groups, with a notable V-shaped shift observed at C11.

Anti-hepatopathy and anti-nephropathy activities of Taraxacum officinale in a rat model of Streptozotocin diabetes-induced hepatorenal toxicity and dyslipidemia via attenuation of oxidative stress, inflammation, apoptosis, electrolyte imbalances, and mitochondrial dysfunction

Diabetes and chronic liver and kidney disease are common long-term conditions worldwide. Taraxacum officinale (TOE) has many medicinal properties, due to it phytochemicals constitutions. This study investigate activities of TOE in Streptozotocin diabetes-Induced Hepatorenal toxicity. Sixty rats were randomized into groups A, B, C, D, E, and F of ten rats each (n = 10). Group normal control, group B treated with TOE, group C diabetic (DM) negative control, group D DM rats treated with TOE, group E DM rats treated with metformin (MF)], group F treated with TOE follow by STZ-diabetic). Serum lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT), total proteins (TP), albumin (ALB), Urea, and creatinine, electrolyte, oxidative and antioxidant enzymes, caspase 3, inflammatory cytokines, tricarboxylic acid (TCA) cycle enzymes and mitochondrial membrane potential (ΔΨm), liver and kidney histology were investigated.Treatment with TOE ameliorated all the electrolyte disruptions in DM rats. Treatment with TOE and TOE + MF recovered caspase 3, inflammatory makers, oxidative and antioxidant enzymes in DM rats. Moreover, an increase in lipid profile, hepatic and renal functional markers, ALT, AST, ALP, GGT, TP, ALB, Urea, TCA and renal mitochondrial respiratory-chain complexes (I-IV) and ΔΨm and a decrease in creatinine clearance was recovered in DM rats by TOE and TOE + MF treatment. TOE and TOE + MF protected against hepatic and renal histological damage in DM group.Hepatorenal toxicity was effectively ameliorated by the TOE administration. TOE might be considered as a potential protective agent against hepatorenal toxicity.

Beneficial Effects of Dietary Flaxseed on Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese male and female rats were studied along with their lean counterparts after 12 weeks of ingestion of a control diet, or control diet with flaxseed, or high fat, high sucrose (HFHS), or HFHS plus flaxseed. Obese rats showed higher liver weight and increased levels of cholesterol, triglyceride, and saturated fatty acid, which were further elevated in rats on the HFHS diet. The HFHS diet induced a significant two-fold elevation in the plasma levels of both aspartate aminotransferase and alanine aminotransferase in the obese male and female rats. Including flaxseed in the HFHS diet significantly lowered liver weight, depressed the plasma levels of both enzymes in the obese male rats, and reduced hepatic cholesterol and triglyceride content as well as improving the fatty acid profile. In summary, including flaxseed in the diet of male and female obese rats led to an improved lipid composition in the liver and significantly reduced biomarkers of tissue injury despite consuming a HFHS chow.

Halogenated bisphenol A derivatives potently inhibit human and rat 11β-hydroxysteroid dehydrogenase 1: Structure-activity relationship and molecular docking.

Chlorinated bisphenol A (BPA) derivatives are formed during chlorination process of drinking water, whereas bisphenol S (BPS) and brominated BPA and BPS (TBBPA and TBBPS) were synthesized for many industrial uses such as fire retardants. However, the effect of halogenated BPA and BPS derivatives on glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) remains unclear. The inhibitory effects of 6 BPA derivatives in the inhibition of human and rat 11β-HSD1 were investigated. The potencies for inhibition on human 11β-HSD1 were TBBPA (IC50, 3.87 μM) = monochloro BPA (MCBPA, 4.08 μM) = trichloro BPA (TrCBPA, 4.41 μM) > tetrachloro BPA (TCBPA, 9.75 μM) > TBBPS (>100 μM) = BPS (>100 μM), and those for rat 11β-HSD1 were TrCBPA (IC50, 2.76 μM) = MCBPA (3.75 μM) > TBBPA (39.58 μM) > TCBPA = TBBPS = BPS. All these BPA derivatives are mixed/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that MCBPA, TrCBPA, TCBPA, and TBBPA all bind to the active site of human 11β-HSD1, forming hydrogen bonds with catalytic residue Ser170 except TCBPA. Regression of the lowest binding energy with IC50 values revealed a significant inverse linear regression. In conclusion, halogenated BPA derivatives are mostly potent inhibitors of human and rat 11β-HSD1, and there is structure-dependent inhibition.

Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans.

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA), bisphenol A (BPA) analogs, are endocrine-disrupting chemicals predominantly metabolized into glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in humans and rats. In the present study, TBBPA and TCBPA glucuronidation by the liver microsomes of humans and laboratory animals (monkeys, dogs, minipigs, rats, mice, and hamsters) and recombinant human hepatic UGTs (10 isoforms) were examined. TBBPA glucuronidation by the liver microsomes followed the Michaelis-Menten model kinetics in humans, rats, and hamsters and the biphasic model in monkeys, dogs, minipigs, and mice. The CLint values based on the Eadie-Hofstee plots were mice (147) > monkeys (122) > minipigs (108) > humans (100) and rats (98) > dogs (81) > hamsters (47). TCBPA glucuronidation kinetics by the liver microsomes followed the biphasic model in all species except for minipigs, which followed the Michaelis-Menten model. The CLint values were monkeys (172) > rats (151) > mice (134) > minipigs (104), dogs (102), and humans (100) > hamsters (88). Among recombinant human UGTs examined, UGT1A1 and UGT1A9 showed higher TBBPA and TCBPA glucuronidation abilities. The kinetics of TBBPA and TCBPA glucuronidation followed the substrate inhibition model in UGT1A1 and the Michaelis-Menten model in UGT1A9. The CLint values were UGT1A1 (100) > UGT1A9 (42) for TBBPA glucuronidation and UGT1A1 (100) > UGT1A9 (53) for TCBPA glucuronidation, and the activities at high substrate concentration ranges were higher in UGT1A9 than in UGT1A1 for both TBBPA and TCBPA. These results suggest that the glucuronidation abilities toward TBBPA and TCBPA in the liver differ extensively across species, and that UGT1A1 and UGT1A9 expressed in the liver mainly contribute to the metabolism and detoxification of TBBPA and TCBPA in humans.

Monocyte chemoattractant protein-1 and cyclooxygenase enzymes in rats treated with drugs of abuse

The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and cyclo-oxygenase-2 enzyme are potent mediators of neuroinflammation. We studied the effect of treatment with Cannabis sativaresin extract and/or tramadol, two common drugs of abuse on the level of MCP-1 in brain and serum of rats. In addition, serum levels of cyclo-oxygenase 1 (COX-1) and cyclo-oxygenase 2 (COX-2) enzymes in rats given cannabis werealso determined. Cannabis sativaresin at 5, 10 or 20 mg/kg (expressed as delta-9-tetrahydrocannabinol), tramadol at 5, 10 or 20 mg/kg or tramadol at 10 mg/kg combined with cannabis at 5-20 mg/kg were given once a day, subcutaneously, for six weeks. Resultsshowed that, as compared to corresponding controls, Cannabis sativa resin produced a significant increase in MCP-1 increased inbrain tissue (29.8-56.4%) and serum (14.8-31.0%). MCP-1 showed also significant increments in brain (34.6%) and serum (22.1%) by 20 mg/kg tramadol. After the concomitant treatment with both cannabis and tramadol, MCP-1 increased in brainby 88.5-145.7%and in serum by 32.6-64.8%. Moreover, cannabis given at 20 mg/kg significantly increasedserum COX-1 and COX-2 by 362% and 58.8% compared to corresponding control values. The histopathological study of the striatum of cannabis-treated animals revealed the presence of apoptotic cells and pyknotic nuclei and congestion of blood vessels. The striatum from animals given tramadol showed neuronal perinuclear cytoplasmic vacuolations and apoptotic cells. Moreover, the combined administration of both cannabis and tramadol resulted in neuronal necrosis, vacuolation, apoptosis and pyknosis. Collectively, these results indicate that treatment with cannabis resin and/or tramadol is associated with a proinflammatory response that involves MCP-1 and cyclooxygenases and which could result in the development of brain injury.

Alleviative effect of sodium butyrate on high-fructose-diet-induced hepatic accumulation of triacylglycerol is associated with reduced expression levels of fructolytic and fatty acid synthetic enzymes in rats

Alleviative effect of sodium butyrate on high-fructose-diet-induced hepatic accumulation of triacylglycerol is associated with reduced expression levels of fructolytic and fatty acid synthetic enzymes in rats