Liver Of Male Wistar Rats Research Articles

Toxicity Assessment of Synthetic Pyrethroids (Lambda Cyhalothrin) on the Liver and Kidney Organs of Male Wistar Rats

Toxicity Assessment of Synthetic Pyrethroids (Lambda Cyhalothrin) on the Liver and Kidney Organs of Male Wistar Rats

The Effect of Ethanol Extract of Ripe Denettia tripetala Fruit (Pepper Fruit) on Indices of Liver and Kidney Function in Male Albino Wistar Rats

The Effect of Ethanol Extract of Ripe Denettia tripetala Fruit (Pepper Fruit) on Indices of Liver and Kidney Function in Male Albino Wistar Rats

CUR-CA-THIONE: A NOVEL CURCUMIN CONCOCTION WITH ENHANCED WATER SOLUBILITY AND BRAIN BIO-AVAILABILITY

<p><strong>Objective: </strong>Curcumin, is widely studied as a potential drug in treating various disorders but lacks applicability due to poor water solubility and tissue bioavailability. The main objective of the study was to develop a formulation of curcumin that has enhanced water solubility and brain bioavailability.</p><p><strong>Methods: </strong>A curcumin concoction was prepared using solvent evaporation technique taking casein and glutathione as vectors. Various process parameters were identified namely time, temperature, pH and vector while formulation parameters included drug entrapment, anti-oxidant activity, and water solubility. The concoctions were evaluated for <em>in vitro</em> release kinetics at three pH i.e. 1.2, 4.5 and 6.2 at six-time intervals i.e. 10, 20, 30, 40, 60, 120 min using dialysis bag membrane. The same kinetics was further validated using same time points with wistar rats and giving concoction at a single dose of 2 g/kg via the oral route.</p><p><strong>Results: </strong>A concoction i.e. CUR-CA-THIONE having significant entrapment efficiency (77.83%, 97.75%, 90.19%), water solubility (40, 350 and 45 times than normal curcumin) and DPPH activity (IC<sub>50</sub>: 28.91, 25.07 and 27.89) was evaluated in concoctions CUR-CA-THIONE-T.1, CUR-CA-THIONE-T.2 and CUR-CA-THIONE-T.3 respectively. These formulations were then carried out for <em>in vitro</em> release profile at different pH with average release obtained between 20-30 min. <em>In vivo</em> kinetics was studied by isolating tissues like brain, liver, lung, kidney and spleen in male wistar rats and maximum brain bioavailability was observed for CUR-CA-THIONE-T.3 at 30 min with 75 ng/g of brain tissue.</p><p><strong>Conclusion: </strong>The experiment helps in concluding that CUR-CA-THIONE has improved its water solubility and is able to by-pass systemic circulation to targeted activity.</p>

Oxidative stress in rat brain but not in liver following oral administration of a low dose of nanoparticulate silver

While it is known that silver nanoparticles (AgNPs) can enter the brain, our knowledge of AgNP-induced neurotoxicity remains incomplete. We investigated the ability of 10 nm citrate-stabilized AgNPs to generate oxidative stress in brain and liver of adult male Wistar rats after repeated oral exposure for 14 days, using a low dose of 0.2 mg/kg b.w. as compared with the same dose of ionic silver (silver citrate). In AgNP-exposed animals, the level of reactive oxygen species (ROS), lipid peroxidation (MDA) and glutathione peroxidase (GPx) activity were found to be significantly higher in brain relative to the control group receiving saline. Administration of ionic silver (silver citrate) increased ROS and MDA levels in both tissues. Activities of GPx in brain so as superoxide dismutase (SOD) and catalase (CAT) in liver of exposed animals were also elevated. Besides, AgNPs and silver ions were both found to cause statistically significant decrease in the reduced-to-oxidized glutathione ratio (GSH/GSSG) in brain. The results show that exposure to a very low dose of particulate silver generates mild oxidative stress in the brain but not in the liver of rats, indicating a role of oxidative stress in AgNP-induced neurotoxicity.

Cytotoxic potentials of thiocyanate administration on the liver of male wistar rats ( RattusNorvegicus )

The use of thiocyanate as an anti-sickling drug is currently on the increase among sickle cell disease (SCD) patients. The continuous use of this substance without sufficient toxicity data does not guaranty continuously functional and healthy internal organs among the SCD patients that are susceptible to multi-organ failure such as hepatic failure. Hence this study was performed to elucidate the consequence(s)of thiocyanate administration on the liver of adult male wistar rats. Twenty adult male wistar rats with an average weight of 234.5g were used. The rats were grouped into four (A, B, C & D) with five animals in each group. Group A represented the control and was given only 1ml of distilled water daily while B,C,&D received 1ml of thiocyanate solution at doses of 10mg/Kg/day, 20mg/Kg/day, & 30mg/Kg/day for twenty-eight (28) days. The administration was carefully done with the use of an oral cannula. Thereafter, the rats were sacrificed via cervical dislocation. The rats were dissected and blood samples were immediately collected from the apex of the heart for the analysis of serum total bilirubin. A fraction of the liver was cut to prepare homogenates for biochemical enzymes (alanine aminotransferase-ALT, aspartate aminotransferase- AST) analysis. Thereafter the animals were wholly perfused with normal saline and then fixed with 4% paraformaldehyde. The fixed liver tissues were then taken for histological assessments. The slide sections (H&E and PAS stains) in the treated groups showed varying degrees (mild to severe disruption of hepatocellular morphology plus prominence and widening of sinusoids) of thiocyanateinduced liver damage. But hepatocellular appearance was normal in the control group. Biochemical assays of serum total bilirubin and tissue AST increased fairly with increasing dose although this was not significant. The increase in tissue level of ALT in group B was also not significant with respect to the control. But increase in ALT level was found to be significant in groups C&D when compared with the control. Therefore, this study can be used to infer that SCN use in sickle cell disease management regimen can cause hepatocellular damage in wistar rats. Key Words : Thiocyanate,Biochemical enzymes,Hepatocellular morphology, Anti-sickling

Relationships between Mechanical Nociceptive Threshold and Activity of Antioxidant Enzymes in Male Rats with Experimental Type I Diabetes Mellitus.

We analyzed the dynamics of neuropathic pain development and changes in catalase and superoxide dismutase (SOD) activities in the brain, liver, and skeletal muscles of male Wistar rats with 1-month streptozotocin-induced diabetes mellitus. A decrease in mechanical nociceptive threshold was revealed that progressed during the disease progress. Insulin treatment restored nociceptive threshold in diabetic animals to the control values. Catalase activity in the liver and skeletal muscles of diabetic rats increased by 1.5 and 2 times, respectively, in comparison with the control, while insulin treatment reduced enzyme activity to the control level. In the brain, catalase activity was reduced by 1.5 times and insulin therapy did affect this parameter. SOD activity in the studied tissues remained unchanged during diabetes and was not affected by insulin therapy. A strong negative correlation between nociceptive threshold in rats and catalase activity in their liver and skeletal muscles was found.

Effect of Delta Sleep-Inducing Peptide on Functional State of Hepatocytes in Rats During Restraint Stress.

We studied the effect of delta sleep-inducing peptide (40, 120, and 360 μg/kg intraperitoneally, 1 h before the experiment) on free radical oxidation in the liver, aminotransferase activity, and total serum protein content in male Wistar rats during restraint stress. Treatment with the peptide in a dose of 40 μg/kg increased catalase and superoxide dismutase (SOD) activities and malonic dialdehyde (MDA) concentration in the liver homogenate of animals subjected to acute stress. No significant changes were found after administration of this peptide in other doses. Under conditions of chronic stress, the peptide in a dose of 40 μg/kg caused the most pronounced effect. Catalase and SOD activities and MDA concentration decreased, while aminotransferase activity and protein content remained unchanged under these conditions. Administration of the peptide in a dose of 120 μg/kg was accompanied by a decrease in SOD activity and MDA concentration, increase in total protein content, and reduction of AST activity. Increasing the peptide dose to 360 μg/kg abolished its effects.

Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats.

Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

Hepato- and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats.

Chronic and acute alcohol exposure has been extensively reported to cause oxidative stress in hepatic and extra-hepatic tissues. Watermelon (Citrullus lanatus) is known to possess various beneficial properties including; antioxidant, anti-inflammatory, analgesic, anti-diabetic, anti-ulcerogenic effects. However, there is a lack of pertinent information on its importance in acute alcohol-induced hepato- and neuro-toxicity. The present study evaluated the potential protective effects of watermelon juice on ethanol-induced oxidative stress in the liver and brain of male Wistar rats. Rats were pre-treated with the watermelon juice at a dose of 4 ml/kg body weight for a period of fifteen days prior to a single dose of ethanol (50%; 12 ml/kg body weight). Ethanol treatment reduced body weight gain and significantly altered antioxidant status in the liver and brain. This is evidenced by the significant elevation of malondialdehyde (MDA) concentration; depletion in reduced glutathione (GSH) levels and an increased catalase (CAT) activity in the brain and liver. There was no significant difference in the activity of glutathione peroxidase (GPX) in the liver and brain.Oral administration of watermelon juice for fifteen (15) days prior to ethanol intoxication, significantly reduced the concentration of MDA in the liver and brain of rats. In addition, water melon pre-treatment increased the concentration of GSH and normalized catalase activity in both tissues in comparison to the ethanol control group. Phytochemical analysis revealed the presence of phenol, alkaloids, saponins, tannins and steroids in watermelon juice. Our findings indicate that watermelon juice demonstrate anti-oxidative effects in ethanol-induced oxidation in the liver and brain of rats; which could be associated with the plethora of antioxidant phyto-constituents present there-in.

Histological and biochemical markers of the liver of male Wistar rats on oral administration of nevirapine suspension

Background: Mechanism of action of nevirapine in the prophylaxis treatment and treatment of HIV-1 may involve elevations in levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and other biomarkers of liver function. This study presents the hepatotoxic effect of nevirapine suspension using animal model.Methods: A total number of 15 male Wister rats were fed normal chow and antiretroviral drug (Nevirapine) for a period of six weeks. The liver organ of the rats were obtained and subjected to histological procedures and biochemical analysis using enzyme assay obtained from Randox Laboratories Limited, Antrim United Kingdom (BT294QY).Results: The wistar rats showed no significant mean body weight difference when compared with the control group. However there was significant difference in the mean values of AST (77.77±3.03) and ALT (89.37±3.19) of the treated rats. Nevirapine treated rats showed significant difference in AST, ALT, and ALP in the single (77.77± 3.03, 31.80±1.73, 43.81 ±1.54) and double (89.37±3.19, 33.38±2.01, 34.64 ±1.02) doses when compared with the controls (75.14 ±2.00, 29.16±0.17, 45.44 ±1.85) respectively. Mild vascular congestion, infiltration of sinusoids by inflammatory cells, and haemorrhage were induced by nevirapine as compared with the control group showing normal vessels without congestion, normal sinusoids appearing normal without infiltration.Conclusion: The liver histology of the rats fed with Nevirapine suspension showed diffused hepatocellular necrosis. Routine check of the drug effect is important as it provides effective life management of HIV infected individuals.Keywords: Nevirapine, Wister rat, Hepatotoxicity, Liver, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP)

Amelioration of Lead-induced Toxicity in Blood, Liver and Kidney Tissues of Male Wistar Rats by Fermented Ofada Rice

The protective effects of ‘ofada’ rice koji (ORK, fermented ofada rice) and ascorbic acid (AA) against lead (Pb)-induced toxicity in the blood, liver and kidney tissues of male Wistar rats was investigated. The animals were divided into four treatment groups (A – D, n = 5). Groups B, C and D were intoxified by intra-peritoneal injection of 75 mg lead acetate/kg body weight. Groups C and D only had their feed mixed with ORK and AA, respectively. The results showed no significant difference in % packed cell volume (PCV) and Pb concentrations. Feeding with ORK and AA significantly decreased alanine aminotransferase activities (36.50 ± 3.54 and 34.02 ± 0.05 UL-1 respectively) compared to Pb-only treated group (85.50 ± 3.25 UL-1). The ferric reducing antioxidant power (FRAP) for organs increased significantly following intake of feeds mixed with ORK and AA; increases in FRAP was higher for ORK-treated group possibly due to increased total flavonoids concentration following fermentation. Furthermore, Pb-induced high plasma creatinine levels decreased upon treatment with feeds mixed with ORK and ascorbic acid. These findings strongly indicated that feed supplementation with ORK by 45% may be more effective at ameliorating the effects of Pb-induced toxicity in tissues compared to supplementation with AA by 2%.

Optimization, Validation and Application of Spectrophotometric Assay for 3-Hydroxy-3-methylglutarylcoenzyme A Reductase Activity

Purpose : To improve the sensitivity and specificity of spectrophotometric 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase activity assay. Methods : Spectrophotometric HMG-CoA reductase detection in male Wistar rat liver microsomes was optimized by applying different conditions, such as reaction buffer pH, NADPH and protein concentration, and preincubation and reaction times. The optimal set of conditions was validated using HMG-CoA reductase inhibitors, namely, pravastatin, fluvastatin, and rosuvastatin. IC 50 was calculated and compared with that of a radiochemical assay. Ginkgo biloba extract’s (GBE50) inhibitory effect on HMG-CoA reductase activity was evaluated using the optimized spectrophotometric protocol. Results : The optimum assay conditions were as follows: reaction buffer pH 7.0, 100 μM NADPH, 50 μM HMG-CoA, and 200 μg/mL microsomal protein. The preincubation and reaction times were 20 and 60 min, respectively, at 37 oC. The IC50 of pravastatin, fluvastatin, and rosuvastatin under the optimum condition was 0.026, 0.015, and 0.007 μM while for radioisotope assay, it was 0.034, 0.049 and 0.0119 μM, respectively. GBE50 significantly inhibited HMG-CoA reductase activity in a concentrationdependent manner (p < 0.05). Conclusion : These results suggest that HMG-CoA reductase activity can be detected using the improved spectrophotometric assay. This assay can facilitate the discovery and development of new HMG-CoA reductase inhibitors in vitro. Keywords : Spectrophotometry, 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity, Cholesterol metabolism, Ginkgo biloba, Pravastatin, Fluvastatin, Rosuvastatin

Temporal relationship between diet-induced steatosis and onset of insulin/leptin resistance in male Wistar rats.

Rats fed with high-fat-high-sucrose (HFHS) diet are known to manifest metabolic syndrome including hyperinsulinemia, hyperleptinemia, hyperglycemia, diabetic dyslipidemia, and hepatic steatosis. The aim of the current study is to determine the temporal relationships between the development of hepatic steatosis and the onset of insulin and leptin resistance in hypothalamus and liver in male Wistar rats (six weeks of age) fed chow or HFHS diet for up to 8 weeks. Fasting plasma glucose, lipids/lipoproteins, insulin and leptin levels were quantified, histopathologic score of hepatic steatosis and inflammation were assessed, and the responses of common checkpoints of insulin and leptin signalling responsible for lipogenesis and gluconeogenesis were analyzed. In addition, acute insulin or leptin administration was performed at different stages of HFHS dieting to determine the responsiveness of the respective signalling pathways. Hyperinsulinemia, hyperglycemia, dyslipidemia, and increased homeostasis model assessment of basal insulin resistance occurred 1-week after HFHS dieting, coinciding with upregulation of suppressor of cytokine signalling 3 in both hypothalamus and liver. However, hepatosteatosis, accompanied with increased expression of sterol regulatory element binding protein 1c and phosphoenolpyruvate carboxykinase, did not manifest until 4- to 8-week after HFHS dieting. Lowered insulin sensitivity (shown by decreased insulin receptor substrate 1 and protein kinase B phosphorylation) occurred approximately 2 weeks prior to leptin resistance (shown by impaired signal transducer and activator of transcription 3 activation) in both the liver and hypothalamus. Acute insulin/leptin administration also demonstrated the impaired insulin or leptin signalling transduction. These data suggest that lowered insulin sensitivity and leptin resistance occurred at least 2–3 weeks earlier than the manifestation of hepatosteatosis in rats fed HFHS diet.

Biochemical and histological changes in liver and kidney in male Wistar albino rats following exposure to Solignum®: a permethrincontaining wood preservative

The present investigation was aimed to determine the effect of sub-chronic exposure to Solignum&lt;sup&gt;®&lt;/sup&gt;, a permethrin-containing wood preservative on biochemical and histological changes in liver and kidneys of male Wistar albino rats. Thirty-two male rats were randomly divided into four groups: control and three treatment concentrations containing 8 rats each. The treatment groups were exposed to Solignum&lt;sup&gt;®&lt;/sup&gt; at dose rates of 100, 200 and 400 mg/kg body weight (BW) respectively per day orally for four weeks. Data obtained from the study showed a progressive increase in the body weight of rats in control whereas, rats treated with different concentrations (100, 200 and 400 mg/kg BW) of Solignum&lt;sup&gt;®&lt;/sup&gt; decreased significantly (≤0.05) especially at the end of the second and fourth week when compared with control. On the other hand, there was a significant decrease in the relative liver weights of rats treated with 100 and 200 mg/kg BW Solignum&lt;sup&gt;®&lt;/sup&gt; while rats treated with 400 mg/kg BW showed a significant increase when compared with control. The relative weight of kidneys in experimental groups increased significantly when compared with control. Biochemical analysis results illustrated that there was a significant increase in marker enzymes namely alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity at the end of the fourth week. Similarly, total bilirubin, serum urea, creatinine and electrolytes (Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt; and Cl&lt;sup&gt;-&lt;/sup&gt;) levels increased in a dose dependent manner in treated rats when compared with untreated control group. Serum total protein decreased significantly in experimental rats when compared with control. However, cholesterol and triglycerides showed no significant difference when compared with control. Histopathological examination of hepatocytes in treated rats was characterized by mild periportal inflammatory cells and cytoplasmic degeneration. Furthermore, histopathological examination of rat kidneys revealed inflammatory cells, congested vessel and interstitial hemorrhage in rats treated with Solignum&lt;sup&gt;®&lt;/sup&gt;. Therefore, this present study is aimed to evaluate the hepatotoxic and nephrotoxic potentials associated with sub-chronic exposure to the commercial pesticide Solignum&lt;sup&gt;®&lt;/sup&gt;.

Protective Effect of Curcumin against the Liver Toxicity Caused by Propanil in Rats.

We investigated the protective effects of curcumin on propanil-induced alterations in biochemical indices in blood and liver of male Wistar rats. The study consisted of four treatment groups, with six animals each, designated as control, propanil (20mg/kg), curcumin(50 mg/kg), and curcumin (50 mg/kg) + propanil (20 mg/kg). Rats were administered their respective doses orally, every other day, for 28 days. Propanil administration elicited significant (P < 0.001) increases in plasma aspartate aminotransferase and alkaline phosphatase activities, by 24% and 56%, respectively, compared to the control. Treatment with propanil elevated bilirubin, creatinine, and total cholesterol levels in rats, but these were not significant relative to controls. Administration of propanil to rats significantly (P < 0.001) increased lipid peroxidation levels. However, catalase activity, vitamin C, and reduced glutathione levels were significantly reduced. Exposure to propanil did not produce any significant changes in packed cell volume, neutrophils, and leukocyte counts. The supplementation of curcumin attenuated the adverse effects of propanil intoxication by reducing lipid peroxidation levels and restored the levels of serum enzymes and reduced glutathione. The present study showed that propanil increased oxidative stress and altered some biochemical parameters in the rats but curcumin could afford some protection to attenuate propanil-induced toxicity in the liver.

OP2-6 - Oxysterols induce mitochondrial impairment and hepatocellular toxicity in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disorder affecting up to 25% of the general population. Several intracellular events leading to NAFLD and progression to non-alcoholic steatohepatitis (NASH) have been identified, including lipid accumulation, mitochondrial dysfunction and oxidative stress. Emerging evidence links both hepatic free fatty acids (FFAs) and cholesterol (FC) accumulation in NAFLD development; in particular oxysterols, the oxidative products of cholesterol, may contribute to liver injury. We performed a targeted lipidomic analysis of oxysterols in the liver of male Wistar rats fed a high-fat (HF), high-cholesterol (HC) or high-fat/high-cholesterol (HF/HC) diet. Both HF and HC diets caused liver steatosis, but the HF/HC diet resulted in steatohepatitis with associated mitochondrial dysfunction. Above all, the oxysterol cholestane-3beta,5alpha,6beta-triol (triol) was particularly increased in the liver of rats fed diets rich in cholesterol. To verify the molecular mechanism involved in mitochondrial dysfunction and hepatocellular toxicity, Huh7 and primary rat hepatocytes were exposed to palmitic acid (PA) and/or oleic acid (OA), with or without triol. This compound induced apoptosis in cells co-exposed to both PA and OA, and this was associated with impaired mitochondrial respiration as well as down-regulation of PGC1-alpha, mTFA and NRF1.In conclusion, our data show that hepatic free fatty acid or oxysterols accumulation per se induce low hepatocellular toxicity. On the contrary, hepatic accumulation of both fatty acids and toxic oxysterols such as triol are determinant in the impairment of mitochondrial function and biogenesis, contributing to liver pathology in NAFLD.

The anabolic androgenic steroid nandrolone decanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats.

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g−1 body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.

Profile of microRNAs associated with aging in rat liver.

Recent studies suggest that small non‑coding microRNAs (miRNAs or miRs) play an important role in the regulation of genes involved in various cellular and developmental processes. However, the expression of miRNAs during the aging process remains largely unknown. The aim of the present study was to analyze miRNA expression profiles in rat livers during the aging process. The livers of male Wistar rats at different stages of development (fetal, aged 3 days, and 1, 2, 4, 8 and 36 weeks of age) were used. Total RNA was extracted from the livers. We analyzed the expression levels of 679 rat miRNA probes. In addition, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) was performed. Several up- and downregulated miRNAs were identified in the rat livers at 7 different fetal developmental stages and at 36 weeks of age. We observed the upregulation of miR‑29a, miR‑29c, miR‑195 and miR‑497, whereas miR‑301a, miR‑148b-3p, miR‑7a, miR‑93, miR‑106b, miR‑185, miR‑450a, miR‑539 and miR‑301b were downregulated in the aging rat livers. The number of PCNA-positive hepatocytes was decreased with age. In conclusion, our findings suggest that these up- and downregulated miRNAs play an important role in aging by regulating cell cycles that are involved in liver senescence. Further investigation is required to reveal additional target genes of the miRNAs expressed in the liver and the roles of miRNAs in the developmental process of aging in the liver.

Effects of hypercholesterolemic diet enriched with onion as functional ingredient on fatty acid metabolism in Wistar rats

The complex biochemical composition of onions has been studied as a source of biological components with health-related properties. The evolution of hypercholesterolemia is associated with a large range of alterations considered as strong risk factors for many cardiovascular events. The objective of this study was to investigate the effects of onion as functional ingredient on plasma, erythrocyte, liver and adipose tissue fatty acid composition in hypercholesterolemic male Wistar rats. Rats (n=24) were randomly divided into three groups: control (C), high-cholesterol (HC), and high-cholesterol enriched with onion (HCO) groups. At the end of 7weeks, animals were anesthetized and euthanized by extracting blood by cardiac puncture. Plasma, erythrocytes, liver and adipose tissue were collected and immediately stored at −80°C. Fatty acid methyl esters were identified and quantified by GC/MS. Total fatty acid concentration decreased in liver and adipose tissue both in HC and HCO groups. SFA content was significantly higher in plasma, erythrocytes and liver in the C group compared to HC and HCO groups. In contrast, SFAs increased in adipose tissue both in HC and HCO groups compared to the C group. A significant increase in MUFA content in plasma was found in HC and HCO groups compared to the C group; in erythrocytes and liver the increase was lower. In plasma, PUFA content was significantly lower in HC and HCO groups compared to the C group. Interestingly, in liver and adipose tissue, PUFAs increased in HC and HCO groups compared to the C group. Results showed noticeable effects on individual fatty acid composition when assaying high-cholesterol diets in rats, in some cases enhanced by onion enrichment. Further research is needed to deeper understand the involved mechanisms and pathways.

Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats.

Chios mastic gum (CMG), a resin derived from Pistacia lentiscus var. chia, is known since ancient times for its pharmacological activities. CYP1A1 and CYP1A2 enzymes are among the most involved in the biotransformation of chemicals and the metabolic activation of pro-carcinogens. Previous studies referring to the modulation of these enzymes by CMG have revealed findings of unclear biological and toxicological significance. For this purpose, the modulation of CYP1A1 and CYP1A2 enzymes in the liver of male Wistar rats following oral administration of CMG extract (CMGE), at the levels of mRNA and CYP1A1 enzyme activity, was compared to respective enzyme modulation following oral administration of a well-known bioactive natural product, caffeine, as control compound known to involve hepatic enzymes in its metabolism. mRNA levels of Cyp1a1 and Cyp1a2 were measured by reverse transcription real-time polymerase chain reaction and their relative quantification was calculated. CYP1A1 enzyme induction was measured through the activity of ethoxyresorufin-O-deethylase (EROD). The results indicated that administration of CMGE at the recommended pharmaceutical dose does not induce significant transcriptional modulation of Cyp1a1/2 and subsequent enzyme activity induction of CYP1A1 while effects of the same order of magnitude were observed in the same test system following the administration of caffeine at the mean daily consumed levels. The outcome of this study further confirms the lack of any toxicological or biological significance of the specific findings on liver following the administration of CMGE.