Liver Of Aged Rats Research Articles

Deacetylation of HnRNP U mediated by sirtuin1 ameliorates aged rat with liver fibrosis via inhibiting p53-related senescence and NLRP3-related inflammation

Senescence represents a major risk factor promoting liver fibrosis progression. Sirtuin 1 (SIRT1), an essential regulator of cellular senescence, may be involved in developing liver fibrosis. However, the role and mechanism of SIRT1 in liver fibrosis development were largely unknown. We constructed the liver fibrosis in aged rats induced by carbon tetrachloride (CCl4) and then transfected with GFP-SIRT1 adenoviral vectors. After that, we performed acetylomic analysis of liver tissue in aged rats to identify potential substrates of SIRT1. Furthermore, replicative senescent rat hepatocytes were pretreated with siRNA HnRNP U, SIRT1 adenoviral vectors, resveratrol, and siRNA SIRT1, following stimulation with H2O2. We found that the protein levels of SIRT1 and HnRNP U were down-regulation in aged rat liver fibrotic tissues, with an accumulation of NLRP3 inflammasome and activation of the p53/p21 pathway in liver tissue, as well as an increased level of plasma IL-1β secretion. In comparison, these effects were reversed by overexpressing SIRT1 with adenoviral vectors. Acetylation of HnRNP U and its sites at K28 and K787 might be potential targets for SIRT1-mediated liver fibrosis in aged rats. Silencing HnRNP U reduced H2O2-induced up-regulation expression of p53, p21, and NLRP3 inflammasome at protein levels. Additionally, H2O2 induced high acetylation of HnRNP U in senescent hepatocytes, whereas overexpressing SIRT1 with adenoviral vectors and resveratrol deacetylate HnRNP U to inhibit NLRP3 inflammasome and the p53/p21 pathway. Besides, the silence of SIRT1 aggravated H2O2-induced p53-related senescence and NLRP3-related inflammation in senescent hepatocytes. Our findings suggested that deacetylation of HnRNPU mediated by SIRT1 attenuated liver fibrosis in the elderly by inhibiting p53/p21 pathway and NLRP3-related inflammation.

Protective Effect of Carvacrol against Oxidative Damage in Aged Rats.

Aging affects cellular functions and impairs tissue homeostasis. Carvacrol, a polyphenolic compound, has been shown to exert a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer characteristics. This investigation aimed to evaluate the effect of carvacrol in elderly male rats. Carvacrol at a dose of 15 or 30 mg/kg was administrated daily per os for 60 days to aged rats. The liver, heart, and kidney samples were taken for the analysis of oxidative stress markers. Serum samples were used to evaluate liver enzymes (alanine transaminase (ALT) and aspartate aminotransferase (AST)). The levels of malondialdehyde (MDA) in the liver, heart, and kidney tissues of aged rats were higher. Conversely, the level of thiol was lower in the mentioned tissues than in the young control group. The levels of MDA in the liver, heart, and kidney tissues of aged rats were significantly reduced by carvacrol, which was accompanied by increased levels of total thiol. ALT and AST levels were higher in the serum of aged rats than in the young control ones. Carvacrol decreased ALT and AST levels in the serum of aged rats versus aged control rats. Carvacrol can be effective in protecting susceptible aged tissues and organs by increasing antioxidant defenses and decreasing liver enzymes.

FoxO6-mediated ApoC3 upregulation promotes hepatic steatosis and hyperlipidemia in aged rats fed a high-fat diet.

FoxO6, an identified factor, induces hyperlipidemia and hepatic steatosis during aging by activating hepatic lipoprotein secretion and lipogenesis leading to increased ApoC3 concentrations in the bloodstream. However, the intricate mechanisms underlying hepatic steatosis induced by elevated FoxO6 under hyperglycemic conditions remain intricate and require further elucidation. In order to delineate the regulatory pathway involving ApoC3 controlled by FoxO6 and its resultant functional impacts, we employed a spectrum of models including liver cell cultures, aged rats subjected to HFD, transgenic mice overexpressing FoxO6 (FoxO6-Tg), and FoxO6 knockout mice (FoxO6-KO). Our findings indicate that FoxO6 triggered ApoC3-driven lipid accumulation in the livers of aged rats on an HFD and in FoxO6-Tg, consequently leading to hepatic steatosis and hyperglycemia. Conversely, the absence of FoxO6 attenuated the expression of genes involved in lipogenesis, resulting in diminished hepatic lipid accumulation and mitigated hyperlipidemia in murine models. Additionally, the upregulation of FoxO6 due to elevated glucose levels led to increased ApoC3 expression, consequently instigating cellular triglyceride mediated lipid accumulation. The transcriptional activation of FoxO6 induced by both the HFD and high glucose levels resulted in hepatic steatosis by upregulating ApoC3 and genes associated with gluconeogenesis in aged rats and liver cell cultures. Our conclusions indicate that the upregulation of ApoC3 by FoxO6 promotes the development of hyperlipidemia, hyperglycemia, and hepatic steatosis in vivo, and in vitro. Taken together, our findings underscore the significance of FoxO6 in driving hyperlipidemia and hepatic steatosis specifically under hyperglycemic states by enhancing the expression of ApoC3 in aged rats.

The relationship between spontaneous cystic degeneration and pseudocapillarization in sinusoids in the liver of aged Sprague-Dawley rats

The relationship between spontaneous cystic degeneration and pseudocapillarization in sinusoids in the liver of aged Sprague-Dawley rats

Integrative analysis of the transcriptome and metabolome reveals the importance of hepatokine FGF21 in liver aging

Aging is a contributor to liver disease. Hence, the concept of liver aging has become prominent and has attracted considerable interest, but its underlying mechanism remains poorly understood. In our study, the internal mechanism of liver aging was explored via multi-omics analysis and molecular experiments to support future targeted therapy. An aged rat liver model was established with d-galactose, and two other senescent hepatocyte models were established by treating HepG2 cells with d-galactose and H2O2. We then performed transcriptomic and metabolomic assays of the aged liver model and transcriptome analyses of the senescent hepatocyte models. In livers, genes related to peroxisomes, fatty acid elongation, and fatty acid degradation exhibited down-regulated expression with aging, and the hepatokine Fgf21 expression was positively correlated with the down-regulation of these genes. In senescent hepatocytes, similar to the results found in aged livers, FGF21 expression was also decreased. Moreover, the expressions of cell cycle-related genes were significantly down-regulated, and the down-regulated gene E2F8 was the key cell cycle-regulating transcription factor. We then validated that FGF21 overexpression can protect against liver aging and that FGF21 can attenuate the declines in the antioxidant and regenerative capacities in the aging liver. We successfully validated the results from cellular and animal experiments using human liver and blood samples. Our study indicated that FGF21 is an important target for inhibiting liver aging and suggested that pharmacological prevention of the reduction in FGF21 expression due to aging may be used to treat liver aging-related diseases.

Effect of Blueberry Extract on Liver in Aged Rats.

Aging and age-related disorders are prominent issues. Aging is associated with a gradual impairment of physiology at the genetic, cellular, tissue, and whole organism level that directly influences the development of chronic diseases and organ failure. Blueberries, on the other hand, are well known for their high content of bioactive compounds and have demonstrated positive impacts on metabolic factors that influence health and general well-being. This study is aimed at evaluating the ameliorating the effects of blueberry on the liver of aged rats by monitoring changes in metabolic disturbances, oxidative stress, and inflammatory disruption. The aged group of rats was orally administered with blueberry extract (200 mg/kg) for a period of 4 weeks. The results revealed that aging was associated with an increase in body weight, liver weight, and metabolic parameters like serum insulin, triglycerides, total cholesterol, and liver function markers accompanied with a decrease in vitamin D levels. Furthermore, the results showed a significant diminish in the activities of antioxidant enzymes, glutathione content with an elevation in lipid peroxidation, inflammatory mediators (tumor necrosis factor alpha, interleukin 6, and nuclear factor kappa-light-chain-enhancer of activated B cells) as well as fibrotic markers (TGF-β1) in the liver of aged rats. Compared to the young rats (control group), blueberry effectively reversed age-mediated disruption of the aforementioned parameters. Hence, blueberries can be used as a potential therapeutic strategy for the management of age-related liver dysfunction and disease.

The Effect of Trehalose in Inhibiting Liver Damage via The Il-6 Pathway in Old Mice

Trehalose is a non-reducing disaccharide consisting of two glucose molecules linked by a 1–1 glycosidic bond. Trehalose can play a role in organ detoxification, antioxidant enzyme activity, reducing lipid peroxidation and reducing the secretion of inflammatory factors TNF-, IL-1β, Il-6, thereby inhibiting liver damage. Because of its role, this study aims to determine the effect of trehalose administration on liver damage through the IL-6 expression pathway with experimental post-test design with control group design. This research was conducted using samples of old rats, namely Wistar rats (Rattus novergicus). The old rats used were 21 male species which were then divided into 3 groups, namely the old control group, the old rat group that was given sucrose, and the old rat group that was given trehalose. Then observed for 8 weeks, namely in March - May 2021 at the Faculty of Medicine, Hasanuddin University Makassar. The results obtained from the 3 groups showed a significant value that the administration of trehalose sugar in elderly mice had an effect on reducing the inflammatory factor IL-6 because it activated autophagy in macrophages thereby reducing cytokine production and vascular inflammation so as to be able to restore all aging mice to a level like observed in young mice. It is also known that aged rat liver, which is characterized by ER UPR activation and inflammatory signaling, decreases nicotinamide and UDP-N-acetyl-hexosamines, and reduces proteasome activity. Therefore, trehalose can be an effective therapeutic strategy against age-related disorders of proteostasis in the liver.

Effect of moxibustion on acupoints at "opening" time on telomere length and expression of liver cell cycle regulators in aging rats

To observe the effects of "lingguibafa" moxibustion performing at the appropriate acupoints at their "opening" time on telomere length，expressions of p53 of tumor supressor genes and retinoblastoma gene(Rb)in the liver of aging rats，so as to explore its mechanisms underlying delaying senescence. Forty male SD rats were randomly divi-ded into normal, model, prevention and treatment groups, with 10 rats in each group. The rat model was established by intrape-ritoneally injection of D-galactose (200 mg/kg) once a day for 42 days. The rats in the prevention group were given "lingguibafa" moxibustion during modeling, while those in the treatment group were given "lingguibafa" moxibustion after modeling. Quantitative real-time PCR was used to detect the telomere length and the mRNA expressions of p53 and Rb，ELISA was used to detect the protein contents of p53 and Rb in the liver tissues. Compared with the normal group, the relative telomere length of the model group was significantly shortened (P<0.01), the mRNA expressions and protein contents of p53 and Rb were significantly increased (P<0.01). After intervention and in comparison with the model group, the relative telomere length of the prevention group and the treatments group were significantly increased (P<0.01), and the expressions of p53 and Rb mRNA and protein contents were significantly reduced (P<0.01, P<0.05). There were no significant difference between the prevention and the treatment groups in the abovementioned indexes (P>0.05). Moxibustion on acupoints at "opening" time can inhibit the shortening of telomere length and the down-regulation of the expressions of p53 and Rb in aging rats, which may contribute to its function in delaying the process of cell senescence.

Does Dietary Restriction of Amino Acids Other Than Methionine Have Any Effects on Peroxide and Superoxide Production Rates, Oxidative Protein and DNA Damage in the Liver and Heart Mitochondria of Aging Rats?

Does Dietary Restriction of Amino Acids Other Than Methionine Have Any Effects on Peroxide and Superoxide Production Rates, Oxidative Protein and DNA Damage in the Liver and Heart Mitochondria of Aging Rats?

EGCG exerts its protective effect by mitigating the release of lysosomal enzymes in aged rat liver on exposure to high cholesterol diet.

The aim is to test the hypothesis whether the cholesterol loaded lysosomes are capable of mediating lysosomal membrane permeabilization (LMP) during aging and to study the efficacy of epigallocatechin-3-gallate (EGCG) in preserving the lysosomal membrane stability. Aged rats were fed with high cholesterol diet (HCD) and treated with EGCG orally. Serum and tissue lipid status, cholesterol levels in lysosomal fraction, activities of lysosomal enzymes in lysosomal, and cytosolic fractions were measured. Transmission electron microscopic studies (TEM), oil red "O" (ORO) staining, and immunohistochemical analysis of oxidized low density lipoprotein (OxLDL) were carried out. Significant increase in serum, tissue lipid profile, and lysosomal cholesterol levels were observed in aged HCD-fed rats with a concomitant decrease in high density lipoprotein (HDL) levels. We also observed a significant increase in lipid accumulation in hepatocytes of aged HCD-fed rats by TEM, ORO, and immunohistochemical staining. Upon treatment with EGCG to aged HCD-fed animals, we found augmented levels of HDL with a concomitant decrease in lysosomal cholesterol levels and other lipoproteins. TEM studies and immunohistochemistry of OxLDL also showed a marked reduction in lipid deposition of hepatocytes. Thus, EGCG has preserved the lysosomal membrane stability in HCD stressed aged rats. SIGNIFICANCE OF THE STUDY: The research article is focused mainly on the effect of EGCG and its capability on mitigating the release of lysosomal enzymes in aged animals fed with HCD. The study signifies the cellular function of the organelle lysosome following administration of aged rats with HCD, which would make the readers to understand the action of EGCG and the interrelationship of both cholesterol and activity of lysosomes when cholesterol is loaded.

Role of 7-chloro-4-(phenylselanyl) quinoline as an anti-aging drug fighting oxidative damage in different tissues of aged rats.

This study investigated whether subacute treatment with 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) presented antioxidant action in oxidative stress associated with aging in different rat tissues. We also investigated whether plasma selenium levels were altered by aging, as well as the contribution of 4-PSQ administration to these levels. Aged Wistar male rats (23month old) were intragastrically treated with 4-PSQ (5mg/kg) for seven days. On the 14th day of the experimental protocol, plasma was collected to determine selenium levels and biochemical markers of renal and hepatic damage. Furthermore, liver, kidney, spleen and cerebral cortex were removed to determine thiobarbituric acid reactive species (TBARS), non-protein thiols (NPSH), glutathione S-transferase (GST), catalase (CAT) and δ-aminolevulinate dehydratase (ALA-D). Our results showed that one or more parameters changed markedly in the liver, kidney, spleen and cerebral cortex of aged rats. Moreover, biochemical markers of renal and hepatic damage and selenium levels are changed in the plasma of aged rats. Treatment with 4-PSQ repaired redox homeostasis in tissues of aged rats, as well as plasma biochemical markers of renal and hepatic damage and selenium levels. In conclusion, 4-PSQ presented an antioxidant effect in tissues of aged rats, restoring selenium levels, and contributing to the restoration of the damage caused by aging. Thus, 4-PSQ could be a potential candidate for the management of age-related oxidative damage, acting as an anti-aging drug.

Altered FoxO1 and PPARγ interaction in age-related ER stress-induced hepatic steatosis.

Chronic kidney disease (CKD) is one of the most powerful predictors of premature cardiovascular disease (CVD), with heightened susceptibility to vascular intimal and medial calcification associated with a high cardiovascular mortality. Abnormal mineral metabolism of calcium (Ca) and phosphate (P) and underlying (dys)regulated hormonal control in CKD-mineral and bone disorder (MBD) is often accompanied by bone loss and increased vascular calcification (VC). While VC is known to be a multifactorial process and a major risk factor for CVD, the view of primary triggers and molecular mechanisms complexity has been shifting with novel scientific knowledge over the last years. In this review we highlight the importance of calcium-phosphate (CaP) mineral crystals in VC with an integrated view over the complexity of CKD, while discuss past and recent literature aiming to highlight novel horizons on this major health burden. Exacerbated VC in CKD patients might result from several interconnected mechanisms involving abnormal mineral metabolism, dysregulation of endogenous calcification inhibitors and inflammatory pathways, which function in a feedback loop driving disease progression and cardiovascular outcomes. We propose that novel approaches targeting simultaneously VC and inflammation might represent valuable new prognostic tools and targets for therapeutics and management of cardiovascular risk in the CKD population.

MHY2013 Modulates Age-related Inflammation and Insulin Resistance by Suppressing the Akt/FOXO1/IL-1β Axis and MAPK-mediated NF-κB Signaling in Aged Rat Liver.

Chronic inflammation is a major risk factor underlying aging and age-associated diseases. It impairs normal lipid accumulation, adipose tissue function, and mitochondrial function, which eventually lead to insulin resistance. Peroxisome proliferator-activated receptors (PPARs) critically regulate gluconeogenesis, lipid metabolism, and the lipid absorption and breakdown process, and PPAR activity decreases in the liver during aging. In the present study, we investigated the ability of 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013), synthesized PPARα/PPARβ/PPARγ pan agonist, to suppress the inflammatory response and attenuate insulin resistance in aged rat liver. Six- and 20-month-old rats were divided into 4 groups: young and old rats fed ad libitum; and old rats fed ad libitum supplemented with MHY2013 (1 mg and 5 mg/kg/d for 4 wk). We found that MHY2013 supplementation efficiently downregulated the activity of nuclear factor-κB through JNK/ERK/p38 mitogen-activated protein kinase signaling in the liver of aged rats. In addition, MHY2013 treatment increased hepatic insulin signaling, and the downstream signaling activity of FOXO1, which is negatively regulated by Akt. Downregulation of Akt increases expression of FOXO1, which acts as a transcription factor and increases transcription of interleukin-1β, leading to hepatic inflammation. The major finding of this study is that MHY2013 acts as a therapeutic agent against age-related inflammation associated with insulin resistance by activating PPARα, PPARβ, and PPARγ. Thus, the study provides evidence for the anti-inflammatory properties of MHY2013, and the role it plays in the regulation of age-related alterations in signal transduction pathways.

Differential Expression of Epidermal Growth Factor Receptor, Hepatocyte Growth Factor Receptor and Hypoxia‐Inducible Factor‐1‐Alpha in Aged Rat Livers

Epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (cMET) and the transcription factor, hypoxia‐inducible factor 1‐ alpha (HIF1‐α) are highly important in angiogenesis, mitogenesis and cell proliferation which are all vital processes required for mammalian liver regeneration. In as much as aging is characterised with general decline in maintenance and function of certain body organs, this is not exactly the same with the liver in regeneration. Aging could result to reduction in the response of the liver to certain extrinsic stimuli such as initiation of stress proteins as a result of injury. To study the effects of age on the expression of these molecules, EGFR, cMET and HIF1‐α gene expression in aged rat liver samples (18months old) vs. young animals (3 months old) was studied through semi and relative quantitative quantification of gene specific mRNA coding for these genes. β‐Actin was used as a reference/housekeeping gene for normalisation of the EGFR, cMET and HIF1‐α genes, the Livak method was used to quantify the relative expression of these genes in relation to the ages of the animals. The results show high mRNA expression of EGFR and cMET in 3 months old samples (young). Analysis of EGFR showed an mRNA fold decrease of 0.56 gene expression and 2.3 for cMET gene express in the 18 months liver. HIF1‐α analysis showed a 5.16 increase in the mRNA gene expression in the 18 month old when compared with the 3 months old. Data from this study show that decrease in expression of epidermal growth factor receptor in the liver with age accelerates decrease in regeneration rate. The fact that EGFR and cMET were expressed at significantly lower levels in older samples reflects the differential decrease in regeneration ability and physiologic activities such proliferation, mitogenesis and angiogenesis in the liver with age. This result in reduction in the ability of the liver to regenerate, thus making the aged liver more susceptible to infections.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

PO-082 16-Week high intensity interval training does not alter LKB1 and AMPKα protein in Rats Liver

Objective Liver, as one of the most important organs involved in lipids and glucose metabolism, yet no study has examined the response of liver kinase B1 (LKB1) and AMP-activated protein kinase α(AMPKα) signaling after high intensity interval training. This study aims to evaluate the effect of 16-week high intensity interval training intervention on the expression of LKB1、AMPKα in liver of aging rats.&#x0D; Methods 8 -month-old male Wistar rats（n=40）were randomly divided into control group (C) and HIIT group (H). Group H with 70%-90%-50%VO2max intensity training for 50min/ day, 5 days / week, lasted for 16 weeks. Rats were killed on 0, 8 and 16 weeks. We examined the protein expression of LKB1 and AMPKα in liver. Proteins were analyzed by western blot analysis. Data are mean±SD; for ANOVA, p&lt;0.05 was significant.&#x0D; Results The AMPKα levels in group C and group H increased with time and there was no significant difference between the groups. The content of LKB1 in group C and group H both increased first and then decreased, but there was no significant difference between the groups.&#x0D; Conclusions 16-week high intensity interval training intervention had no effect on LKB1, AMPKα protein expression in aging rats.

Protective Effect of remote ischemic preconditioning on liver warm ischemia-reperfusion injury in aged rats

Objective To investigate the effect of remote ischemic preconditioning on nuclear factor erythroid-2 related factor 2 (Nrf2) signaling in the liver of aged rats after warm ischemia reperfusion injury. Methods A 70% hepatic warm ischemia-reperfusion model was established in aged rats (15-16 months old) (1 hour after ischemia and 2 hours after reperfusion). 12 male Sprague-Dawley rats were divided into two groups: pretreatment group and control group. The level of serum alanine aminotransferase (ALT) was detected after operation and the liver tissues were harvested for the determination of malondialdehyde (MDA) content and the activity of antioxidant enzyme-superoxide dismutase (SOD). The pathological changes of liver were observed. The change of Nrf2 protein expression in liver tissue was examined by Western blot . Results Serum ALT and MDA in the pretreatment group were significantly lower than those in the control group. The liver pathological damage of pretreatment group rats were lighter than the control group (P<0.05). Compared with the control group, the Nrf2 protein expression and the activity of SOD increased in the liver of pretreatment group (P<0.05). Conclusions Remote ischemic preconditioning can reduce 70% hepatic ischemia-reperfusion injury in aged rats, and its mechanism may be related to its activation of Nrf2 signaling pathway. Key words: Ischemic preconditioning/MT; Warm ischemia/AE; Reperfusion injury/ET/PC; Liver; Rats

Antioxidant SMe1EC2 modulates pentose phosphate pathway and glutathione-dependent enzyme activities in tissues of aged diabetic rats.

The pentose phosphate pathway and glutathione-associated metabolism are the main antioxidant cellular defense systems. This study investigated the effects of the powerful antioxidant SMe1EC2 (2-ethoxycarbonyl-8-methoxy-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b] indolinium dichloride) on pentose phosphate pathway (PPP) and glutathione-dependent enzyme activities in aged diabetic and aged matched control rats. Diabetes was induced by streptozotocin injection in rats aged 13–15 months. Diabetic and control rats were divided into two subgroups, one untreated and one treated with SMe1EC2 (10 mg/kg/day, orally) for 4 months. SMe1EC2 ameliorated body weight loss, but not hyperglycemia of aged diabetic rats. Diabetes resulted in decreased glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD) and glutathione-S-transferase (GST), yet in unchanged glutathione reductase (GR) in the liver of aged diabetic rats. In the liver of the aged control rats, SMe1EC2 did not affect G6PDH, 6PGDH and GR, but it inhibited GST. SMe1EC2 also failed to affect diabetes-induced decline in 6PGDH, it ameliorated G6PDH but produced further decline in GST in the liver of aged diabetic rats. In the kidney of aged rats, G6PDH and GST were found to be comparable among the groups, but diabetes up-regulated 6PGDH and GR; these alterations were prevented by SMe1EC2. In the heart of aged diabetic rats, while GST remained unchanged, the recorded increase in G6PD, 6PGD, GR was prevented by SMe1EC2. Furthermore, an unchanged GR and remarkable increases in G6PD, 6PGD and GST were found in the lung of the aged diabetic group. These alterations were completely prevented by SMe1EC2. The results suggest that in aged rats SMe1EC2 can ameliorate the response of the kidney, heart and lung but not that of the liver against diabetes-induced glucotoxicity by interfering with the activity of redox network enzymes.

Antiglycation and anti-oxidant efficiency of carnosine in the plasma and liver of aged rats.

Increases in oxidative stress and advanced glycation end-products (AGE) formation play an important role in the pathogenesis of aging. Carnosine (CAR; β-alanyl-L-histidine) has anti-oxidant and antiglycating properties. We investigated the effect of CAR supplementation on AGE levels, and protein and lipid oxidation products in the serum and liver tissue in aged rats. Young (3months-of-age) and aged (20months-of-age) rats were injected with CAR (250mg/kg/daily; i.p.; 5days per week) for 2months. At the end of this period, AGE, protein carbonyl, advanced oxidized protein products, and malondialdehyde levels were determined in the serum and liver tissue. Furthermore, reactive oxygen species formation and ferric reducing anti-oxidant power values were measured. AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation were higher in the serum and liver tissue of aged rats compared with young rats. CAR treatment was observed to significantly decrease AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation in the serum and liver of aged rats. These results clearly show that CAR might be useful for decreasing glycoxidant stress in aged rats. Geriatr Gerontol Int 2017; 17: 2610-2614.

Aging promotes neoplastic disease through effects on the tissue microenvironment

A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes.

Preventive Effect of Carvacrol Against Oxidative Damage in Aged Rat Liver

The present study was designed to investigate the changes in activities of antioxidant enzymes and lipid peroxidation level in the liver of 2, 10 and 20 months old rats, and to see whether these changes are restored to those of the two month old rats after carvacrol treatment. Male rats of 2, 10, and 20 months (n = 10 for each group) were used for all the experiments. The aged rats (10 and 20 months old) were given carvacrol (15 mg/day per body weight) for 30 days. Control animals received an equal volume of vehicle. After the treatment, livers were removed for estimation of superoxide dismutase-SOD, glutathione-S-transferase-GST, catalase-CAT activities and lipid peroxidation level. The present findings determined that normal aging was associated with a significant decrease in the activities of antioxidant enzymes (SOD; 11.87 ± 0.6 (2 months old) vs 7.56 ± 0.1 (20 months old); P < 0.001) in liver, as well as an increase in lipid peroxidation level (MDA; 0.15 ± 0.01 (2 months old) vs 0.41 ± 0.01 (20 months old); P < 0.001) in aged rats. Also, the results of this study indicated that carvacrol treatment increased the activities of the antioxidant enzymes in 20 months old animals versus the aged matched control group (SOD; 9.87 ± 0.4; P < 0.01). Furthermore, carvacrol decreased lipid peroxidation content in 10 and 20 months old animals compared with the aged matched control (MDA; 9.87 ± 0.4; P < 0.001). Our data shows that carvacrol could be a candidate to inhibit the development of age-induced liver damage through inhibition of oxidative stress and also increasing antioxidant defenses.