Rat Liver Enzyme Research Articles

Melatonin administration differentially affects age-induced alterations in daily rhythms of lipid peroxidation and antioxidant enzymes in male rat liver

A central clock/pacemaker, suprachiasmatic nuclei of the hypothalamus coordinates and entrains circadian oscillations in the peripheral tissues such as the liver, kidney, heart, lungs etc. called peripheral clocks. These also have endogenous circadian oscillations. The circadian rhythms of antioxidants present in cytosol signify redox state of the cell during day/night cycle. The liver has a major impact on homeostasis through its control on serum protein composition and plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products and undergoes substantial changes in structure and function upon aging. In present study, the temporal patterns of oxidative stress indicators in liver were studied. Daily rhythms of lipid peroxidation end products, reduced glutathione (GSH), oxidized glutathione (GSSG) and antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were studied in liver at variable time points (Zeitgeber Time (ZT) 0, 6, 12 and 18) in three age groups: 3 (adult), 12 and 24months old male Wistar rats. There was increase in oxidative stress in 12 and 24months old rats indicated through a significant increase in lipid peroxidation, decrease in GSH/GSSG ratio and antioxidant enzyme activities. In 3months old rats, lipid peroxidation was maximum at ZT-12 whereas GSH, SOD and CAT activities were minimum at ZT-12. The maximum level in 24h i.e., acrophases of lipid peroxidation, GPx, SOD and CAT activities in liver cell free extracts altered upon aging. As melatonin, messenger of darkness, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging we studied the effects of melatonin on activities of these antioxidant enzymes in aging rats. Melatonin administration resulted in differential restoration of acrophases, amplitude, mean as well as daily rhythms of lipid peroxidation and antioxidants in liver of 12 and 24months old rats.

Lipid Profile and Antioxidant Enzymes in Normal and Stressed Rat Fed with Palm Olein

Problem statement: The objective of the study was to evaluate the effect of Red Palm Olein (RPO) and Palm Olein (PO) on lipid profile and antioxidant enzyme in normal and stressed rat. Approach: Thirty six Sprague Dawley male rats which were randomly divided into six groups of 6 rats per group (tree normal groups and three stressed groups) were treated with 15% of RPO and PO for four weeks. Results: The results at 4 weeks of treatment showed a decline in Low Density Lipoprotein Cholesterol (LDL-C) level at RPO and PO for normal and stressed groups compared to the control group. The High Density Lipoprotein Cholesterol (HDL-C) level increased in RPO and PO of the normal and stressed groups. There was significant decreased (p?0.05) in the TC in RPO normal group for 4 weeks of treatment compared to the control group while the TC in PO was within the normal range and increased in stressed group. After 4 weeks of treatment the study indicated that there was no significant (p?0.05) effect on antioxidant enzyme (superoxide dismutase) in stressed rat liver but there was a significant decreased (p?0.05) on catalase in stressed rat liver. Conclusion: These results could be due to the high content of vitamin E (tocopherols and tocotrienols) and ?-carotene in red palm olein.

Effects of Aqueous Extract of Nauclea latifolia Stem on Lipid Profile and Some Enzymes of Rat Liver and Kidney

Effects of Aqueous Extract of Nauclea latifolia Stem on Lipid Profile and Some Enzymes of Rat Liver and Kidney

Comparative Analysis of In Vitro Rat Liver Metabolism of the Antimalarial Primaquine and a Derived Imidazoquine

The present study provides proof-of-concept regarding the expectedly high enzymatic stability of primaquinederived imidazolidin-4-ones, imidazoquines, formerly developed as alternatives to the parent antimalarial with potentially improved oral bioavailability [J. Med. Chem., 2009, 52, 7800-7807]. This study provides relevant experimental evidence on the remarkably low propensity of imidazoquines to undergo metabolic conversions mediated by rat liver enzymes. This, together with favourable key ADME parameters previously predicted for these compounds [Bioorg. Med. Chem. Lett. 2009, 19, 6914-6917], and proven lack of acute toxicity in mice, further reinforces the role of imidazoquines as reference leads for the development of novel primaquine surrogates. This is a particularly relevant issue in the present status of malaria chemotherapy worldwide, where primaquine remains the sole drug in clinical use able to block transmission between infected persons and the insect vector and to effectively act on liver-stage parasite forms, including hypnozoites.

Effects of chitosan oligosaccharides on drug-metabolizing enzymes in rat liver and kidneys

To investigate the effect of chitosan oligosaccharides (COS) on drug-metabolizing enzymes in rat liver and kidneys, male Spraque–Dawley rats were fed a diet containing 1% or 3% COS for 5weeks. The activities of cytochrome P450 (CYP) enzymes, UDP-glucurosyltransferase (UGT) and glutathione S-transferase (GST) in the liver and kidneys were determined. Significant decreases in microsomal CYP3A-catalyzed testosterone 6β-hydroxylation, CYP2C-catalyzed diclofenac 4-hydroxylation, and CYP4A-catalyzed lauric acid 12-hydroxylation in the liver of rats fed the COS diets were observed compared with those rats fed the control diet. Immunoblot analyses of CYP proteins showed the same trend as with enzyme activities. Increased glutathione content in liver was found in rats fed the 1% COS diet. Increased hepatic NADPH: quinone oxidoreductase 1 (NQO1) activity was found in rats fed the COS diets. In kidneys, COS had little or no effect on CYP enzyme activities. However, increased GST activity was observed in rats fed the COS diets. Moreover, a higher UGT activity was found in rats fed the 1% COS diet. Our results indicate that COS may suppress hepatic CYP enzymes and induce phase II detoxifying reactions in the liver and kidneys of rats.

Arsenic decreases RXRα-dependent transcription of CYP3A and suppresses immune regulators in hepatocytes

Arsenite is critical pharmacologically as a treatment for advanced stage blood cancer. However, environmental exposure to arsenic results in multiple diseases. Previous studies have shown that arsenic decreases expression of CYP3A, a critical drug metabolizing enzyme in human and rat liver. In addition, acute and chronic arsenic exposure in liver stimulates an inflammatory response. Our work has shown that arsenite decreases nuclear levels of RXRα the nuclear receptor that, as a heterodimer partner with PXR, transactivates the CYP3A gene. These results suggest that arsenite decreases transcription of CYP3A by decreasing RXRα. The present report shows that exposure to 5μM arsenite decreased the activity of a rat CYP3A promoter luciferase reporter in HepG2 cells. The activity of a RARE-luciferase reporter, that is transactivated by the retinoic acid receptor (RAR)/RXRα, was also decreased. Previous studies have shown that arsenic in the concentration range of 2–5μM affects CYP3A mRNA. When rifampicin-treated primary human hepatocyte cultures were exposed to arsenite concentrations as low as 50nM, CYP3A mRNA was decreased. Treatment of primary human hepatocytes with the proteasome inhibitor MG132 increased RXRα suggesting the involvement of the proteasome pathway in regulation of RXRα. Finally, arsenic induces a pro-inflammatory response in liver. Surprisingly, we show that in hepatocytes arsenite decreases expression of two inflammatory mediators, TNF and VEGF, an effect that is not predicted from suppression of RXRα activity.

Changes of activity and kinetics of certain liver and heart enzymes of hypothyroid and T3-treated rats

Thyroid diseases are one of the most common metabolic disorders in the human population. In this work, we present data concerning changes in the activity and kinetic parameters of several enzymes associated with both anabolic (glucose-6-phosphate dehydrogenase-G6PDH, EC 1.1.1.49; 6-phosphogluconate dehydrogenase-6PGDH, EC 1.1.1.44; malic enzyme-ME, EC 1.1.1.40; and isocitrate dehydrogenase-IDH, EC 1.1.1.42) and catabolic (NAD-dependent malate dehydrogenase-NAD-MDH, EC 1.1.1.37; and lactate dehydrogenase-LDH, EC 1.1.1.27) processes under conditions of hypothyroidism and T(3) treatment. Hypothyroidism was induced in rats by the surgical removal of the thyroid gland. T(3)-treated rats were injected by T(3) (0.5 mg T(3)/kg body weight daily during 10 days). We have found that T(3) treatment caused an increase of NAD-MDH activity as well as heart hypertrophy whereas the activity of LDH increased in the direction of pyruvate reduction. Moreover, we observed increased activity of both enzymes in the liver. These results confirm earlier observation concerning the relevance of oxidative metabolism in the heart under T(3) treatment. Hypothyroidism resulted in changes in the LDH activity in the heart whereas NAD-MDH activity did not change. Moreover, our data show that T(3) treatment caused an increase of G6PDH, 6PGDH, and ME activities in the liver. We also observed a decrease of IDH activity in both organs, whereas hypothyroidism caused the opposite effect. This data indicate that either deficiency or excess of thyroid hormones can prove to be particularly dangerous for the physiology of the heart muscle by disturbing bioenergetic and anabolic processes.

Evaluation of the effects of hydroalcoholic extract of Berberis vulgaris root on the activity of liver enzymes in male hypercholesterolemic rats.

Hyperlipidemia can cause a variety of diseases such as atherosclerosis, diabetes, and fatty liver which is followed by increased liver enzymes. Since Berberis vulgaris (B. vulgaris) root possesses antioxidant properties, the present study was conducted to investigate the effect of its extract on the activity of liver enzymes in rats. In this experimental study, sixty Wistar rats were selected and allocated to six groups of ten each. The control group received a normal diet and the sham group received a fatty diet while the other groups including experimental groups received a fatty diet and the alcoholic extract of B. vulgaris at minimum (75 mg/kg), moderate (150 mg/kg), and maximum (300 mg/kg) doses by intraperitoneal injection (i.p.) or oral atorvastatin (10 mg /kg) with a fatty diet. At the end of this 21-day period, blood samples were drawn and the levels of the intended factors were measured. Data were analyzed using SPSS software version 11.5. The comparison of the obtained results showed that the levels of alanine transaminase (ALT) and alkaline phosphatase (ALP) enzymes in the sham group that only received fatty food increased (p≤0.05), whereas in the treatment groups receiving B. vulgaris extract as well as in the group receiving Atorvastatin, these enzymes significantly decreased; however, no significant changes were observed in aspartate transaminase (AST) levels. Noticing the antioxidant properties of B. vulgaris root extract and its effects on reducing the activity of liver enzymes, the extract of this plant can be a good choice for improving the function of liver.

Hepatoprotective Effect of Garlic Homogenate Co-Administered with Anti-Tuberculosis Drugs in RatLiver Enzymes

Hepatoprotective Effect of Garlic Homogenate Co-Administered with Anti-Tuberculosis Drugs in RatLiver Enzymes

Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic rats

In this work, we studied liver morphology, markers of hepatic oxidative stress and some liver enzymes in diabetic rats treated with the combined leaf extract (CLE) of Vernonia amygdalina (bitter leaf) and Azadirachta indica (neem). Diabetes was induced in fasted male Wistar rats with intraperitoneal injection of streptozotocin (STZ). Oral CLE (500 mg/kg body weight) and metformin (150 mg/kg body weight) were administered to different groups of diabetic rats for eight weeks. Blood glucose and change in body weight were estimated weekly. All animals were sacrificed under anaesthesia after eight weeks. Hepatic sections were stained with periodic acid-Schiff. Liver samples were homogenized and assayed for contents of malondialdehyde (MDA) and glutathione peroxidase (GPx), while the plasma was assayed for contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Metformin and CLE treatment produced normoglycaemia in the diabetic rats in the course of the treatment period. Significant increases in body weight were observed in the treatment groups compared with the diabetic control rats (P<0.05). In the control and treatment groups, light microscopic study showed intact hepatic histology. Plasma ALT and AST were not significantly different from the control values in the CLE-treated rats. In addition, from week four onwards, blood glucose concentrations in the CLE-treated rats were not different from the normal control (P>0.05). Besides, hepatic MDA (P<0.05) significantly decreased in the CLE-treated rats compared with the normal control. These findings suggest that CLE ameliorates hyperglycemia and hepatic oxidative stress when administered to diabetic rats as a chronic regimen, and there was no morphologic or biochemical evidence of liver damage at the dose tested.

Effect of mosquito mats (pyrethroid-based) vapor inhalation on rat brain cytochrome P450s

The effect of transfluthrin (TF) or D-allethrin (DA) pyrethroid (PYR) vapors, often contained as main ingredients in two commercially available mosquito repellent mats, on cytochrome P450 (CYP) enzymes of rat brain and liver was assessed. Immunodetection of CYP2E1 and CYP3A2 proteins revealed their induction in cerebrum and cerebellum, but not in liver microsomes of rats exposed by inhalation to TF or DA. This overexpression of proteins correlated with an increase of their catalytic activities. The specifically increased expression of CYP isoenzymes, due to PYR exposure in the rat brain, could perturb the normal metabolism of endogenous and xenobiotic compounds and leads to increased risks of neurotoxicity by bioactivation, lipid peroxidation and DNA damage.

Identification of hypoglycaemic compounds from berries of Juniperus oxycedrus subsp. oxycedrus through bioactivity guided isolation technique

Ethnopharmacological relevanceDecoction of Juniperus oxycedrus subsp. oxycedrus L. (Cupressaceae) berries is used internally as tea and pounded fruits are consumed to lower blood glucose levels in Turkey. Aim of the studyTo evaluate hypoglycaemic and antidiabetic activity of J. oxycedrus subsp. oxycedrus berries and to identify active compounds through bioactivity guided isolation technique. Material and methodsHypoglycaemic effect of J. oxycedrus subsp. oxycedrus (Joso) berry extracts on oral administration was studied using in vivo models in normal, glucose-hyperglycaemic rats. Streptozotocin induced diabetic rats were used to examine antidiabetic activity of Joso extracts, subextracts, fractions, subfractions and shikimic acid (SA). ResultsThrough in vivo bioactivity-guided fractionation processes, shikimic acid, 4-O-β-d-glucopyranosyl ferulic acid and oleuropeic acid-8-O-β-d-glucopyranoside were isolated from the n-butanol subextract by silica gel and reverse phase column chromatography as the main active ingredient of the active subfraction. After 8 days administration of the major compound shikimic acid, blood glucose levels (24%), malondialdehyde levels in kidney tissues (63–64%) and liver enzymes (AST, ALT, ALP) of diabetic rats were decreased. ConclusionResults indicated that Joso berry extract and its active constituents might be beneficial for diabetes and its complications.

Effect of water extract from traditional Chinese medicines Rehmannia glutinosa, Scrophularia ningpoensis, Asparagus cochinchinensis and Ophiopogon japonicas on contents of CYP450 and activities of CYP3A,CYP2E1 and CYP1A2 in rat

To study the effects of the water extract of Rehmannia glutionsa, Scrophularia ningpoensis, Asparagus cochinchinensis and Ophiopogon japonicas, which are the drug from Tianwang Buxin Wan from nourishing vin, on the content of cytohrome P450 (CYP450) in rat and the activities of CYP3A, CYP2E1 and CYP1A2 to investigate the role of CYP450 in the biotransformation of Tianwang Buxin Wan. The rats were killed after administrated with extracts once daily for consecutive 7 days, the livers were removed rapidly and weighed, liver microsomes were prepared with ultra-centrifuge method, the contents of liver microsomal CYP450, cytochrome b5 (Cytb5) and the activities of CYP3A were examined by ultraviolet spectrophotometry, the activities of CYP2E1 and CYP1A2 were determined by high performance liquid chromatography (HPLC). All groups had no difference in the levels of liver indexe compared with normal sodium group. The water extract of R. glutionsa obviously decreased the contents of P450 (P < 0.01) and increased the activity of CYP3A (P < 0.01) and CYP1A2 (P <0.05). The water extract of S. ningpoensis decreased the contents of P450 (P < 0.05) and significantly increased CYP3A and CYP1A2 activities (P < 0.01). A. cochinchinensis increased content of Cytb5 (P < 0.05) in rat and increased the activity of CYP2E1 (P < 0.05) and CYP1A2 (P < 0.01). O. japonicas had no significant difference on the contents of CYP450 and Cytb5 while increased the activities of CYP3A (P < 0.05), CYP2E1 (P < 0.05) and CYP1A2 (P < 0.01). R. glutionsa and S. ningpoensis could decrease the content of CYP450 enzyme in rat liver and induct the activities of CYP3A and CYP1A2. A. cochinchinensis could induct the activities of CYP2E1 and CYP1A2. O. japonicus could induction the activities of CYP3A, CYP2E1 and CYP1A2 in Tianwang Buxin Wan. By inhibiting CYP450 activity to decrease the metabolism of other drugs, the effect of other functional groups in the compatibility of Tianwang Buxin Wan can be enhanced, and a theoretical basis on studying the compatible mechanism can be provided.

Effects of desipramine on the antioxidant status in rat tissues at carrageenan‐induced paw inflammation

The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG injection into the right hind paw resulted in a time-dependent increase in the paw volume; the maximum of CG-induced edema peak was in 2-4 h. A single DES dose of 20 mg · kg(-1) , administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg · kg(-1) ) suppressed the edematous response to CG. The latter drug dose protected CG-induced decrease of glutathione (non-enzyme antioxidant) in the liver; it did not affect CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of glutathione-conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS-generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries.

Effect of Di-(2-ethylhexyl)-phthalate on Sphingolipid Metabolic Enzymes in Rat Liver

Di-(2-ethylhexyl)-phthalate (DEHP), the most widely utilized industrial plastizer and a ubiquitous environmental contaminant, can act on peroxisome proliferators-activated nuclear hormone receptor family (PPAR) isoforms. To understand the contribution of sphingolipid metabolism to DEHP-induced hepatotoxicity, effect of DEHP exposure on activities of sphingolipid metabolic enzymes in rat liver was investigated. DEHP (250, 500 or 750 mg/kg) was administered to the rats through oral gavage daily for 28 days. The activities of acidic and alkaline ceramidases were slightly increased in 250 mg/kg DEHP-administered rat livers and significantly elevated in 500 mg/kg DEHP-administered ones, although the level of 750 mg/kg DEHP-administered ones was not increased. Neutral ceramidase, acidic and neutral sphingomyelinases, sphingomyeline synthase and ceramide syhthase were not changed at all by DEHP exposure. Therefore, acidic and alkaline ceramidases might play important roles in DEHP-induced hepatotoxicity.

Effect of margarine on liver enzymes (ALT and AST) in rats

Effect of margarine on liver enzymes (ALT and AST) in rats

Effects of aqueous extract of Nauclea latifolia stem on lipid profile and some enzymes of rat liver and kidney

Effects of aqueous extract of Nauclea latifolia stem on lipid profile and some enzymes of rat liver and kidney

Synthesis of some novel triazoloquinazolines and triazinoquinazolines and their evaluation for anti-inflammatory activity

A series of triazoloquinazolines and triazinoquinazolines were synthesized as novel anti-inflammatory agents. Some of the newly synthesized compounds 8, 11, and 19 showed good anti-inflammatory activities. Also, the median lethal doses (LD50s) of compounds 8, 11, and 19 in mice were 222.25, 213.25, and 235 mg/100 g b.w., respectively. Oral administration of compounds 8, 11, and 19 to the rats at dose of 300 mg/kg b.w. for 10 days showed non-significant changes in liver enzymes SGOT, SGPT, ALP, LDH, γ-GT, SOD, GPx, and blood GSH and serum TBARs as compared with the control group. But, administration of indomethacin orally to the rats at a concentration of 600 mg/kg b.w. daily for 10 days to rats showed significant increase in serum SGOT, SGPT, ALP, LDH, γ-GT, and TBARs and significant decrease in blood GSH, SOD, and GPx. These findings suggest that compounds 8, 11, and 19 exhibited good anti-inflammatory activity and more safe on liver enzymes in rats.

The effect of lipid-depletion on the kinetic properties of rat liver monoamine oxidase-B.

The extraction of lipids from rat liver mitochondrial membranes by 2-butanone treatment inhibited the activity of membrane-bound monoamine oxidase -A but not -B. For the -B form, the apparent Michaelis constants of the enzyme towards oxygen and the maximum molecular turnover numbers obtained when beta-phenethylamine and benzylamine were used as substrates were not significantly changed by the lipid-depletion procedure, but the values of the Michaelis constant towards benzylamine was significantly increased after lipid-depletion. The differential sensitivity of beta-phenethylamine and benzylamine oxidation to inhibition by Tris-HCl was not changed after lipid-depletion. The results are consistent with the hypothesis that the mitochondrial membrane lipids, while essential for the activity of the -A form of the enzyme in rat liver, play a more subtle modulatory role in the activity of the -B form.

Identification of monohydroxylated metabolites of cannabidiol formed by rat liver.

Cannabidiol (CBD) was metabolized in vitro by rat liver enzymes. Unchanged CBD and eight monohydroxylated metabolites were isolated and positively identified. As previously reported, 7-hydroxy-CBD was the major metabolite. The second most abundant metabolite was 6alpha-hydroxy-CBD; whereas only a trace amount of 6beta-hydroxy-CBD was found. In addition hydroxylation occurred in all positions of the pentyl side chain, 4 inches-hydroxy-CBD being most abundant. 3 inches-Hydroxy-CBD was formed in half of the yield of 4 inches-hydroxy-CBD, while 1 inches-, 2 inches-, 5 inches-hydroxy-CBD were each formed in approximately one fourth of the yield of 4 inches-hydroxy-CBD.