Rabbit Enzyme Research Articles

Influence of Cinnamon Supplementation on Liver Enzymes in Male Rabbits

The liver, a vital organ in the body, plays a central role in managing the metabolism of both internal and external substances. It is crucial for drug processing and detoxification; however, it is vulnerable to damage from foreign chemicals, alcohol intake, poor nutrition, environmental pollutants, illnesses, and various medications. Besides being commonly used as a spice, the inner bark of cinnamon (Cinnamomum zeylanicum L.) has gained popularity for its applications in disease prevention and treatment. Current evidence has indicated potential health benefits associated with cinnamon intake; however, its effects on liver function remain unclear. Therefore, this systematic review and meta-analysis aimed to investigate the effects of cinnamon supplementation on liver enzymes in male rabbits. Relevant studies were identified through a comprehensive search of PubMed/Medline, Scopus, Web of Science, Cochrane Library, and Embase databases up to September 2023. Ten male New Zealand White rabbits were randomly divided into two groups: (1) a control group, and (2) a group treated with cinnamon at a dose of 200 mg/kg body weight. Blood samples and liver homogenates were used to assess liver function markers in both serum and liver tissue. The results showed that cinnamon treatment led to a significant (P<0.05) reduction in the activity of blood plasma and liver enzymes "LDH", "AST", and "ALT", while "ALP" and "AcP" levels significantly (P<0.05) increased compared to the control group. Further high-quality studies are necessary, especially in populations with abnormal liver enzyme levels, to more definitively establish the clinical efficacy of cinnamon on liver function.

Gentamicin Induced Damage in Nephrotoxicity and Hepatotoxicity in Male Rabbits: The Protective Effect of Cinnamon

One common aminoglycoside antibiotic that is well-known for its ability to treat gram-negative bacterial infections is gentamicin. Its nephrotoxic and hepatotoxic side effects, which are mostly brought about by the production of free radicals that harm kidney and liver cells, frequently restrict its therapeutic application. On the other hand, strong antioxidants found in cinnamon, a popular spice and therapeutic plant, have been demonstrated to have protective properties against oxidative stress. In order to assess the protective role of cinnamon, the current study examines how cinnamon affects gentamicin-induced changes in biochemical markers, liver enzymes in male rabbits. Treatment groups included a control group, a gentamicin-only (GIN) group, a cinnamon-only (CIN) group, and a combined cinnamon-gentamicin (CIN+GIN) group. The results showed that GIN group elevated liver enzymes, specifically aspartate transaminase (AST) and alanine transaminase (ALT), suggesting possible hepatotoxicity. The dose of cinnamon decreased these enzyme levels, while the combination therapy kept the AST levels close to control. Biochemical examination revealed that cinnamon reduced these alterations, particularly in the combination therapy group, while gentamicin increased total protein, urea, and creatinine levels, indicating renal and hepatic stress. The study concludes by highlighting the potential of cinnamon in reducing gentamicin-induced toxicity, specifically through its effects on lipid profiles, liver enzyme activities, body weight, blood profiles, and biochemical markers. This suggests that cinnamon could be used as an adjuvant therapy to reduce the negative effects of gentamicin".

Structural basis of increased binding affinities of spikes from SARS-CoV-2 Omicron variants to rabbit and hare ACE2s reveals the expanding host tendency.

The potential host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been expanding alongside its evolution during the pandemic, with rabbits and hares being considered important potential hosts, supported by a report of rabbit sero-prevalence in nature. We measured the binding affinities of rabbit and hare angiotensin-converting enzyme 2 (ACE2) with receptor-binding domains (RBDs) from SARS-CoV, SARS-CoV-2, and its variants and found that rabbit and hare ACE2s had broad variant tropism, with significantly enhanced affinities to Omicron BA.4/5 and its subsequent-emerged sub-variants (>10 fold). The structures of rabbit ACE2 complexed with either SARS-CoV-2 prototype (PT) or Omicron BA.4/5 spike (S) proteins were determined, thereby unveiling the importance of rabbit ACE2 Q34 in RBD-interaction and elucidating the molecular basis of the enhanced binding with Omicron BA.4/5 RBD. These results address the highly enhanced risk of rabbits infecting SARS-CoV-2 Omicron sub-variants and the importance of constant surveillance.IMPORTANCEThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has swept the globe and caused immense health and economic damage. SARS-CoV-2 has demonstrated a broad host range, indicating a high risk of interspecies transmission and adaptive mutation. Therefore, constant monitoring for potential hosts is of immense importance. In this study, we found that Omicron BA.4/5 and subsequent-emerged sub-variants exhibited enhanced binding to both rabbit and hare angiotensin-converting enzyme 2 (ACE2), and we elucidated the structural mechanism of their recognition. From the structure, we found that Q34, a unique residue of rabbit ACE2 compared to other ACE2 orthologs, plays an important role in ACE2 recognition. These results address the probability of rabbits/hares being potential hosts of SARS-CoV-2 and broaden our knowledge regarding the molecular mechanism of SARS-CoV-2 interspecies transmission.

Ameliorating effect of probiotic on nonalcoholic fatty liver disease and lipolytic gene expression in rabbits

Nonalcoholic fatty liver disease (NAFLD) is a condition that affects about 24% of people worldwide. Increased liver fat, inflammation, and, in the most severe cases, cell death are all characteristics of NAFLD. However, NAFLD pathogenesis and therapy are still not clear enough. Thus, this study aimed to determine the effect of a high-cholesterol diet (HCD) inducing NAFLD on lipolytic gene expression, liver function, lipid profile, and antioxidant enzymes in rabbits and the modulatory effects of probiotic Lactobacillus acidophilus (L. acidophilus) on it. A total of 45 male New Zealand white rabbits, eight weeks old, were randomly divided into three groups of three replicates (5 rabbits/replicate). Rabbits in group I were given a basal diet; rabbits in group II were given a high-cholesterol diet that caused NAFLD; and rabbits in group III were given a high-cholesterol diet as well as probiotics in water for 8 weeks. The results showed that a high-cholesterol diet caused hepatic vacuolation and upregulated the genes for lipoprotein lipase (LPL), hepatic lipase (HL), and cholesteryl ester transfer protein (CETP). Downregulated low-density lipoprotein receptor (LDLr) gene, increased liver enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)], cholesterol, triglycerides (TG), low-density lipoprotein (LDL), glucose, and total bilirubin. On the other hand, it decreased high-density lipoprotein (HDL), total protein, albumin, and liver antioxidants [glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)]. Supplementing with probiotics helped to return all parameters to normal levels. In conclusion, probiotic supplementation, especially L. acidophilus, protected against NAFLD, and restored lipolytic gene expression, liver functions, and antioxidants to normal levels.

Effect of different concentration of Single and Multi -Walled Carbon Nanotubes in liver texture and hepatic enzymes in the New Zealand white rabbit

The aim of the present study was to investigate the effect of variable doses of single and multiwalled carbon nanotubes (SWCNTs and MWCNTs) instilled intratracheally on texture of liver and hepatic enzymes ,alanine amino transferase (ALT) and aspartate amino transferase (AST) in New Zealand white rabbits. In this study was used 70 males New Zealand white rabbits, their ages range between (12-18 months) divided into seven groups, ten for each group which instilled with Nanoparticles, At days 7 and 90 post exposure, The blood and tissue samples were collected for each group.
 Instillation of SWCNTs ( 1 or 5 mg/ml/kg (b.w) or MWCNTs (1,3or 5 mg/ml/kg b.w) in the trachea of rabbits induced a significant increase in activity of ALT and AST.
 Translocation of carbon nanotubes was seen from the lungs to the liver. It was concluded that: SWCNTs and MWCNTs induced hepatic injuries through its effect in activity of hepatic enzyme and the nanotubes translocated from the lung to the liver and pleura.
 

Study the antioxidant effect of coconut oil in rabbits treated with sodium nitrate

The present study was conducted to explore the effect of different concentrations of coconut oil as an antioxidant with rate of (1.5, 2 ,2.5ml/kg) of body weight given orally and measure Hematological parameters (white blood cells,PCV , Hb and platelets) and biochemical parameters (cholesterol and its different kinds (Total cholesterol, HDL, LDL, VLDL), triglycerides) and liver enzymes (Superoxide dismutase , Glutathione) in rabbits that demonstrated sodium nitrate as oxidative material use concentration (75 mg / kg), and compared to all results with control group . The results showed a decrease in triglycerides, LDL , SOD and GSH , increase HDL cholesterol levels and a raise in the number of white blood cells, platelets and Hb level this results belong to increase the number of free radicals as a result of oxidative stress caused by the use of sodium nitrate.

Paracetamol as organic compound induced the decrease in the antioxidant enzymes and thiobarbituric acid-reactive substances in male rabbits

Paracetamol is accessible as a nonspecific medicine, with brand names counting Tylenol and Panadol among others. In 2019, it was the 145th most commonly prescribed medication in the world, with more than 4 million prescriptions. Therefore, the present study has been carried out to investigate the paracetamol toxicity on lipid peroxidation andd antioxidant enzymes in male New Zealand white rabbits. Animals were assigned to one of two treatment groups: 0 mg paracetamol kg BW [control]; 500 mg paracetamol/kg BW. Rabbits were orally managed the particular dosages each other day for 12 weeks. Results obtained showed that paracetamol significantly [P < 0.05] induced thiobarbituric acid-reactive substances [TBARS; the marker of lipid peroxidation] in plasma, while the activities of glutathione S-transferase [GST], superoxide dismutase [SOD] and catalase [CAT], and the level of sulfhydryl groups [SH-group] were decreased [P < 0.05] in blood plasma. Keywords: Paracetamol; TBARS; Glutathione S-Transferase; Rabbits

Regulation of skeletal muscle AMP deaminase. Carbethoxylation of His-51 belonging to the zinc coordination sphere of the rabbit enzyme promotes its desensitization towards the inhibition by ATP

BackgroundSkeletal muscle AMP deaminase (AMPD1) regulates the concentration of adenine nucleotides during muscle contraction. We previously provided evidence that rabbit AMPD1 is composed by two HPRG 73 kDa subunits and two 85 kDa catalytic subunits with a dinuclear zinc site with an average of two histidine residues at each metal site. AMPD1 is mainly expressed in fast twitching fibers and is inhibited by ATP. The limited trypsinization of the 95-residue N-terminal domain of rabbit AMPD1 desensitizes the enzyme towards ATP inhibition at the optimal pH 6.5, but not at pH 7.1. MethodsThe modified residues of rabbit AMPD1 after incubation with radioactive diethyl pyrocarbonate ([14C]DEP) causing the desensitization to inhibition by ATP at pH 7.1 have been identified by sequence analysis and MS analysis of the radioactive peptides liberated from the carbethoxylated enzyme by limited proteolysis with trypsin. ResultsThe study confirms the presence of a dinuclear zinc site in rabbit AMPD1 and shows that carbethoxylation of His-51 at the N-terminus of the catalytic subunit removes the inhibition of the enzyme by ATP at pH 7.1. ConclusionsThe desensitization to ATP is due to the modification of His-51 of the Zn2 coordination sphere which is transduced in a conformational change of the enzyme C-terminus, where an ATP-binding site has been localized. General significanceThe progress in the study of the complex regulation of rabbit AMPD1 that shares an identical amino acid sequence with the human enzyme is important in relation to the role of the enzyme during mammalian evolution.

Ameliorative potential of resveratrol on live body weight, glycaemic profile and serum liver enzymes in cholesterol diet-fed rabbits

Ameliorative potential of resveratrol on live body weight, glycaemic profile and serum liver enzymes in cholesterol diet-fed rabbits

Effect of Salvia miltiorrhiza aerial parts on growth performance, nutrient digestibility, and digestive enzymes in rabbits.

ObjectiveThis study aimed to investigate the effect of Salvia miltiorrhiza (S.m.) aerial parts as an alternative ingredient on growth performance, nutrient digestibility, and digestive enzymes in growing rabbits.MethodsTreatments included five tested diets: a control (basal diet), antibiotic (basal diet +enramycin at 5 mg/kg), and S.m. aerial parts powder added at 3.0%, 6.0%, and 9.0% of feed using 300 growing rabbits.ResultsThe diets with S.m. aerial parts addition at 9.0% decreased (p<0.05) feed/gain compared to the control, but there were no differences in feed intake and body weight gain. In contrast with the control, the addition of antibiotic increased (p<0.05) digestibility of dry matter, crude protein, energy, fiber, and ash. The herb addition did not cause differences in the digestibility of most nutrients compared to the antibiotic, but fiber digestibility of the herb at 6.0% and 9.0% was lower (p<0.05) than that of the antibiotic. Moreover, the antibiotic and the herb also similarly increased (p<0.05) the activities of duodenal α-amylase, maltase, lipase, and trypsin, compared to the control, and the herb at 6.0% and 9.0% showed a greater (p<0.05) activity of elastase than the dose 3.0%.ConclusionThe obtained data indicate that S.m. aerial parts can be a potential forage in rabbit’s diet at 9.0% with a beneficial regulation on nutrition and digestion.

Carboxylesterase Activities and Protein Expression in Rabbit and Pig Ocular Tissues.

Hydrolytic reactions constitute an important pathway of drug metabolism and a significant route of prodrug activation. Many ophthalmic drugs and prodrugs contain ester groups that greatly enhance their permeation across several hydrophobic barriers in the eye before the drugs are either metabolized or released, respectively, via hydrolysis. Thus, the development of ophthalmic drug therapy requires the thorough profiling of substrate specificities, activities, and expression levels of ocular esterases. However, such information is scant in the literature, especially for preclinical species often used in ophthalmology such as rabbits and pigs. Therefore, our aim was to generate systematic information on the activity and expression of carboxylesterases (CESs) and arylacetamide deacetylase (AADAC) in seven ocular tissue homogenates from these two species. The hydrolytic activities were measured using a generic esterase substrate (4-nitrophenyl acetate) and, in the absence of validated substrates for rabbit and pig enzymes, with selective substrates established for human CES1, CES2, and AADAC (d-luciferin methyl ester, fluorescein diacetate, procaine, and phenacetin). Kinetics and inhibition studies were conducted using these substrates and, again due to a lack of validated rabbit and pig CES inhibitors, with known inhibitors for the human enzymes. Protein expression levels were measured using quantitative targeted proteomics. Rabbit ocular tissues showed significant variability in the expression of CES1 (higher in cornea, lower in conjunctiva) and CES2 (higher in conjunctiva, lower in cornea) and a poor correlation of CES expression with hydrolytic activities. In contrast, pig tissues appear to express only CES1, and CES3 and AADAC seem to be either low or absent, respectively, in both species. The current study revealed remarkable species and tissue differences in ocular hydrolytic enzymes that can be taken into account in the design of esterase-dependent prodrugs and drug conjugates, the evaluation of ocular effects of systemic drugs, and in translational and toxicity studies.

The study of angiotensin converting enzyme isolation from crossbred rabbit lung and enzyme storage capacity in frozen conditions

The study was carried out to obtain angiotensin converting enzyme (ACE) with high specific activity and to evaluate the ability to maintain enzyme activity in extract products as well as in rabbit lungs using frozen condition. In the scope of the content, the study conducted an evaluation to select the appropriate extraction solvent of four solvents including acetone, ethanol, Tris-HCl and distilled water. Initially, the research results have helped determine distilled water as the suitable extraction solvent and the difference is not statistically significant compared to Tris-HCl solvent. Angiotensin converting enzyme extract that was obtained by distilled water solvent has a specific activity of 10.35 U/g protein. In addition, the study investigated the ability to maintain angiotensin converting enzyme activity in rabbit lung and crude enzyme product during frozen storage (-18±2°C). The results of the study showed that angiotensin converting enzyme activity could be maintained for 3 months in rabbit lungs and 4 months in the crude product. Besides, the study also used ammonium sulfate with different concentrations to conduct angiotensin converting enzyme collection from extract product. The results of this content help determine the use of saturated ammonium sulfate with concentrations of 50% to 60% for the highest efficiency. The precipitation process helped obtain ACE products with a purity of 4.22 times, the specific activity of 42.64 U/g protein and the recovery rate of ACE up to 29.37%.

Extended Cleavage Specificities of Rabbit and Guinea Pig Mast Cell Chymases: Two Highly Specific Leu-Ases.

Serine proteases constitute the major protein content of mast cell (MC) secretory granules. These proteases can generally be subdivided into chymases and tryptases based on their primary cleavage specificity. Here, we presented the extended cleavage specificities of a rabbit β-chymase and a guinea pig α-chymase. Analyses by phage display screening and a panel of recombinant substrates showed a marked similarity in catalytic activity between the enzymes, both being strict Leu-ases (cleaving on the carboxyl side of Leu). Amino acid sequence alignment of a panel of mammalian chymotryptic MC proteases and 3D structural modeling identified an unusual residue in the rabbit enzyme at position 216 (Thr instead of more common Gly), which is most likely critical for the Leu-ase specificity. Almost all mammals studied, except rabbit and guinea pig, express classical chymotryptic enzymes with similarly extended specificities, indicating an important role of chymase in MC biology. The rabbit and guinea pig are the only two mammalian species currently known to lack a classical MC chymase. Key questions are now how this major difference affects their MC function, and if genes of other loci can rescue the loss of a chymotryptic activity in MCs of these two species.

Rabbit dehydrogenase/reductase SDR family member 11 (DHRS11): Its identity with acetohexamide reductase with broad substrate specificity and inhibitor sensitivity, different from human DHRS11

Human dehydrogenase/reductase SDR family member 11 (DHRS11) has been recently reported to be an NADP+-dependent 3(17)β-hydroxysteroid dehydrogenase, and its orthologs are predicted in genomic analyses of various animals. Among them, the amino acid sequence of predicted rabbit DHRS11 shares 92% identity with that of human DHRS11 and matches peptide sequences (composed of total 87 amino acids) of rabbit heart acetohexamide reductase (RHAR) previously reported. However, the physiological role of RHAR remains unknown, because its known substrates are only acetohexamide and 1,4-naphthoquinone. To elucidate whether the two rabbit enzymes are identical, we have isolated the cDNA for rabbit DHRS11, which was abundantly detected in the brain, heart, kidney and intestine by RT-PCR. The recombinant rabbit DHRS11 reduced acetohexamide and 1,4-naphthoquinone, and was inhibited by tolbutamide and phenobarbital (RHAR-specific inhibitors), demonstrating its identity with RHAR. Rabbit DHRS11 also reduced α-dicarbonyl compounds, aldehydes and aromatic ketones (acetylbenzenes and acetylpyridines), and exhibited 3(17)β-hydroxysteroid dehydrogenase activity. It was competitively inhibited not only by tolbutamide and phenobarbital, but also more potently by several non-steroidal anti-inflammatory drugs such as diclofenac and sulindac. The broad substrate specificity and inhibitor sensitivity were different from those of human DHRS11, which did not reduce aliphatic aldehydes and aromatic ketones despite its higher 3(17)β-hydroxysteroid dehydrogenase activity, and was insensitive to tolbutamide, phenobarbital and diclofenac. The site-directed mutagenesis of Thr163 and Val200 in human DHRS11 to the corresponding residues (Gly and Leu, respectively) in rabbit DHRS11 suggested that these residues are pertinent to the differences in properties of rabbit and human DHRS11s.

Assessment of neuropharmacological potential of low molecular weight components extracted from Rhinella schneideri toad poison.

Background:Studies on toad poison are relevant since they are considered a good source of toxins that act on different biological systems. Among the molecules found in the toad poison, it can be highlighted the cardiotonic heterosides, which have a known mechanism that inhibit Na+/K+-ATPase enzyme. However, these poisons have many other molecules that may have important biological actions. Therefore, this work evaluated the action of the low molecular weight components from Rhinella schneideri toad poison on Na+/K+-ATPase and their anticonvulsive and / or neurotoxic effects, in order to detect molecules with actions of biotechnological interest.Methods: Rhinella schneideri toad (male and female) poison was collected by pressuring their parotoid glands and immediately dried and stored at -20 °C. The poison was dialysed and the water containing the low molecular mass molecules (< 8 kDa) that permeate the dialysis membrane was collected, frozen and lyophilized, resulting in the sample used in the assays, named low molecular weight fraction (LMWF). Na+/K+ ATPase was isolated from rabbit kidneys and enzyme activity assays performed by the quantification of phosphate released due to enzyme activity in the presence of LMWF (1.0; 10; 50 and 100 µg/mL) from Rhinella schneideri poison. Evaluation of the L-Glutamate (L-Glu) excitatory amino acid uptake in brain-cortical synaptosomes of Wistar rats was performed using [3H]L-glutamate and different concentration of LMWF (10-5 to 10 µg/µL). Anticonvulsant assays were performed using pentylenetetrazole (PTZ) and N-methyl-D-aspartate (NMDA) to induce seizures in Wistar rats (n= 6), which were cannulated in the lateral ventricle and treated with different concentration of LMWF (0.25; 0.5; 1.0; 2.0; 3.0 and 4.0 µg/µL) 15 min prior to the injection of the seizure agent.Results:LMWF induced a concentration-dependent inhibition of Na+/K+-ATPase (IC50% = 107.5 μg/mL). The poison induces an increased uptake of the amino acid L-glutamate in brain-cortical synaptosomes of Wistar rats. This increase in the L-glutamate uptake was observed mainly at the lowest concentrations tested (10-5 to 10-2 µg/µL). In addition, this fraction showed a very relevant central neuroprotection on seizures induced by PTZ and NMDA.Conclusions:LMWF from Rhinella schneideri poison has low molecular weight compounds, which were able to inhibit Na+/K+-ATPase activity, increase the L-glutamate uptake and reduced seizures induced by PTZ and NMDA. These results showed that LMWF is a rich source of components with biological functions of high medical and scientific interest.

The rabbit as an orthologous small animal model for APOBEC3A oncogenesis

APOBEC3 are cytidine deaminases that convert cytidine to uridine residues. APOBEC3A and APOBEC3B enzymes able to target genomic DNA are involved in oncogenesis of a sizeable proportion of human cancers. While the APOBEC3 locus is conserved in mammals, it encodes from 1–7 genes. APOBEC3A is conserved in most mammals, although absent in pigs, cats and throughout Rodentia whereas APOBEC3B is restricted to the Primate order. Here we show that the rabbit APOBEC3 locus encodes two genes of which APOBEC3A enzyme is strictly orthologous to human APOBEC3A. The rabbit enzyme is expressed in the nucleus and the cytoplasm, it can deaminate cytidine, 5-methcytidine residues, nuclear DNA and induce double-strand DNA breaks. The rabbit APOBEC3A enzyme is negatively regulated by the rabbit TRIB3 pseudokinase protein which is guardian of genome integrity, just like its human counterpart. This indicates that the APOBEC3A/TRIB3 pair is conserved over approximately 100 million years. The rabbit APOBEC3A gene is widely expressed in rabbit tissues, unlike human APOBEC3A. These data demonstrate that rabbit could be used as a small animal model for studying APOBEC3 driven oncogenesis.

Crystal Structure of CYP2B6 in Complex with an Efavirenz Analog.

The over two dozen CYP2B structures of human, rabbit, and woodrat enzymes solved in the last decade have significantly enhanced our understanding of the structure-function relationships of drug metabolizing enzymes. More recently, an important role has emerged for halogen-π interactions in the CYP2B6 active site in substrate selectivity, explaining in part the preference for halogenated ligands as substrates. The mechanism by which such ligands interact with CYP2B enzymes involves conserved phenylalanine side chains, in particular F108, F115, or F297, in the active site, which form π bonds with halogens. To illustrate such halogen-π interactions using drugs that are major substrates of CYP2B6, we present here a crystal structure of CYP2B6 in complex with an analog of the widely used anti-HIV drug efavirenz, which contains a methyl group in place of the carbonyl oxygen. The chlorine of the efavirenz analog forms a π bond with the aromatic ring of F108, whereas the putative metabolism site on the distal end of the molecule is oriented towards the heme iron. The crystal structure showcases how CYP2B6 accommodates this important drug analog of considerable size in the active site by movement of various side chains without substantially increasing the active site volume. Furthermore, the CYP2B6-efavirenz analog complex provides a useful platform to investigate computationally as well as biophysically the effect of genetic polymorphisms on binding of the widely studied efavirenz.

Dynamics of liver enzymes in rabbits experimentally infected with Fasciola sp. (Intermediate form from Japan).

Dynamics of serum liver enzymes in rabbits experimentally infected with metacercariae of Fasciola sp. (intermediate form between Fasciola hepatica and F. gigantica) were monitored. Gradual increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed from 3 weeks post-inoculation (WPI) and peaked at 6 WPI, which corresponded well to the period of migration and development of juvenile fluke in the liver parenchyma and the time when the young adult flukes migrated to the bile duct. However, no significant increase in serum gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were observed. This could reflect reduced or minimal injury of bile ducts and biliary epithelia as the flukes had reached the adult stage. Alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were not detected in the infected rabbit during the course of the experiment. Serum liver enzymes monitoring might be useful for understanding the host-parasite relationship in fascioliasis.

Effect of aqueous extract of &lt;i&gt;Thymus serpyllum&lt;/i&gt; on lipid profile and some liver enzymes in alloxan-induced diabetic rabbit

&lt;p class="Abstract"&gt;The present study was designed to evaluate the effects of aqueous extract of&lt;em&gt; Thymus serpyllum&lt;/em&gt; on lipid profile and some liver enzymes level in the diabetic rabbit. Rabbits were made diabetic with a single intravenous injection of alloxan and were divided into groups. Group 1 and 2 served as normal and diabetic control, respectively. Group 3 and 4 were given standard drugs glibenclamide and acarbose respectively while Group 5 was treated with 500 mg/kg of extract for 30 days. Blood samples were taken on day 0 and 30. The extract significantly reduced the level of serum cholesterol, triglyceride, LDLs, VLDLs, alkaline phosphatase and transaminases without affecting the HDLs level. Total cholesterol/HDL-cholesterol ratio was significantly reduced as compared to diabetic control. It is conceivable that&lt;em&gt; T. &lt;/em&gt;serpyllum possesses antihyperlipidemic and hepatoprotective effects in diabetic rabbit.&lt;/p&gt;

Ligand characterization of CYP4B1 isoforms modified for high-level expression in Escherichia coli and HepG2 cells.

Human CYP4B1, a cytochrome P450 monooxygenase predominantly expressed in the lung, inefficiently metabolizes classical CYP4B1 substrates, such as the naturally occurring furan pro-toxin 4-ipomeanol (4-IPO). Highly active animal forms of the enzyme convert 4-IPO to reactive alkylating metabolite(s) that bind(s) to cellular macromolecules. By substitution of 13 amino acids, we restored the enzymatic activity of human CYP4B1 toward 4-IPO and this modified cDNA is potentially valuable as a suicide gene for adoptive T-cell therapies. In order to find novel pro-toxins, we tested numerous furan analogs in in vitro cell culture cytotoxicity assays by expressing the wild-type rabbit and variants of human CYP4B1 in human liver-derived HepG2 cells. To evaluate the CYP4B1 substrate specificities and furan analog catalysis, we optimized the N-terminal sequence of the CYP4B1 variants by modification/truncation and established their heterologous expression in Escherichia coli (yielding 70 and 800 nmol·l-1 of recombinant human and rabbit enzyme, respectively). Finally, spectral binding affinities and oxidative metabolism of the furan analogs by the purified recombinant CYP4B1 variants were analyzed: the naturally occurring perilla ketone was found to be the tightest binder to CYP4B1, but also the analog that was most extensively metabolized by oxidative processes to numerous non-reactive reaction products.