• The Korean Journal of Physiology and Pharmacology
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• v.25 no.2
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• pp.131-137
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• 2021

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.

• Journal of Korean Biological Nursing Science
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• v.24 no.2
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• pp.77-85
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• 2022

Purpose: Aging process comes with cognitive impairment due to decreased neuronal cell number, activity, and neuronal circuit. Alteration of inhibitory neurons contributes to cognitive impairment in normal aging and is responsible for disrupting the excitation/inhibition balance by reducing the synthesis of gamma-aminobutyric acid (GABA). Morus nigra (Mulberry) is a natural physiologically active substance that has been proven to have anti-oxidant, anti-diabetic, and anti-inflammatory effects through many studies. This study aimed to evaluate the effects of the mulberry extract (ME) on cognitive function through anti-oxidant enzyme and GABAergic neuronal activity in aged rat brain. Methods: Sprague Dawley rats were randomly assigned as the young group (8 weeks, n= 8), aging group (67 weeks, n= 8), and aging+ mulberry extract group (67 weeks, n= 8). The aging+ mulberry extract group was orally administered 500 mg/kg/d mulberry extract for 6 weeks. Results: The aging+ mulberry extract group improved spatial and short-term memory. The antioxidant potential of ME increased the expression of superoxide dismutase-1 (SOD-1) and decreased inducible nitric oxide synthase (iNOS). Also, the aging+ mulberry extract group significantly increased the expression of GABAergic interneuron in hippocampus cornu ammonis1 (CA1) compared to the aging group. Conclusion: The number of GABAergic inhibitory interneurons was deceased and memory functions in the aging process, but those symptoms were improved and restored by mulberry extract administration.

• Biomedical Science Letters
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• v.5 no.2
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• pp.201-208
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• 1999

To evaluate an effect of growth periods on the bromobenzene-induced liver damage, bromobenzene was administrated to 5-week-old rats and 10-week-old rats pretreated with bromobenzene 5 times every other day for 10 days and then the animals were sacrificed. The results were obtained as follows; The increasing rate of serum levels of alanine aminotransferase, xanthine oxidase activity, hepatic lipid peroxide contents, liver weight per body weight (％) and decreasing rate of hepatic contents of protein to each control group were higher in 10-week-old rats than 5-week-old rats by the pretreatment of bromobenzene. According to the above results, 10-week-old rats indicated more severe liver injury than 5-week-old those in case of bromobenzene pretreatment. On the other hand, hepatic aniline hydroxylase activity was more increased in 10-week-old rats than 5-week-old rats both in control and bromobnezene pretreated rats where as the reverse in hepatic glutathione S-transferase. In case of hepatic GSH determination at the intervals of 2, 4, 8, 24 hours throughout 24 hr after administration of single dose of bromobenzene to 5-week-old and 10-week-old rats both in control and bromobnezene pretreated, the rate of GSH utilization was lower in 10-week-old rats than 5-week-old rats. In conclusion, from the above experimental, it is deduce that the 10-week-old rats showed more severe liver injury than 5-week-old rats by the bromobenzene treatment because the disposal ability of bromobenzene in liver was lower in 10-week-old rats than 5-week-old rats.

• Journal of Nutrition and Health
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• v.31 no.4
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• pp.716-728
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• 1998

To investigate the effect of dietary Ca levels on metabolic changes of Ca and skeleton in postmenopausal women, 10-month-old ovariectomized female rats were compared with 2 month old rats. The rats were fed either 0.2% or 1.2% Ca diets for 16 weeks. Food intake and weight gain as higher in rats fed high Ca diets and in ovariectomized rats. Apparent Ca absorption as higher, and Ca balance was lower in the low Ca groups. Vertebrae density was higher in old rats or those fed a high Ca diets. The old rats and ovariectomized rats showed decreased bone formation, increased bone resorption and kidney function deterioration resulting in increased urinary Ca excretion. Contradictory to the above observation, old rats and ovariectomized rats still showed higher bone mass and bone ash content. Therefore aging was not fully onging in 10-month-old rats. Bone weights, mineral contents, and mineral/wt ratio were lower in ovariectomized rats. Dietary Ca level did not affect urinary Ca excretion, urinary protein excretion, GFR, serum alkaline phosphatase, or urinary hydroxyporline excretion. This means that dietary Ca level did not influence kidney function or bone turnover. However Ca content and the ash content of femur, 4th vertebra, and scapula were increased in high Ca groups. Therefore, it is considered that decreased bone formation and accelerated bone resorption may account for the increased osteoporotic risk in women in menopause after middle age. However, Ca metabolism can be improved and bone components can be maintained if Ca is supplemented.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.1-6
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• 2006

To evaluate whether metformin restores leptin sensitivity in aged rats with leptin resistance, we measured leptin sensitivity in aged (2 year old) and adult (5 month old) rats after 4 weeks of treatment with metformin (300 mg/kg/D, mixing in drinking water), by measuring food intake, body weight and visceral fat losing effects. Leptin ($15{\mu}g/D$) was administered by intracerobroventricular (i.c.v.) infusion through osmotic minipump for 1 week. Metformin treatment decreased body weight and daily food intake in both adult and aged rats compared with their control rats, however, these effects were more prominent in aged rats than in adult rats. Anorexic and fat losing responses following i.c.v. leptin were attenuated in aged rats compared to adult rats. However, these responses of aged rats to leptin were restored by metformin treatment. Moreover, serum concentration of leptin in aged rats was significantly decreased by combined treatment with metformin and leptin. These results suggest that metformin enhances leptin sensitivity in aged rat model, and that combination therapy with metformin and leptin would be helpful for treatment of aging-associated obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.3
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• pp.89-94
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• 2008

In order to reproduce chronic cerebral hypoperfusion as it occurs in human aging and Alzheimer's disease, we introduced permanent, bilateral occlusion of the common carotid arteries (BCCAO) in rats (Farkas et al, 2007). Here, we induced BCCAO in two different rat strains in order to determine whether there was a strain difference in the pathogenic response to BCCAO. Male Wistar and Sprague-Dawley (SD) rats (250-270 g) were subjected to BCCAO for three weeks. Kluver-Barrera and cresyl violet staining were used to evaluate white matter and gray matter damage, respectively. Wistar rats had a considerably higher mortality rate (four of 14 rats) as compared to SD rats (one of 15 rats) following BCCAO. Complete loss of pupillary light reflex occurred in all Wistar rats that survived, but loss of pupillary light reflex did not occur at all in SD rats. Moreover, BCCAO induced marked vacuolation in the optic tract of Wistar rats as compared to SD rats. In contrast, SD rats showed fewer CA1 hippocampal neurons than Wistar rats following BCCAO. These results suggest that the neuropathological process induced by BCCAO takes place in a region-specific pattern that varies according to the strain of rat involved.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.5
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• pp.283-287
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• 2006

Although estrogen is known to playa role in fatty acid metabolism, it remains unclear whether fatty acid oxidation in mature female rats differs from fatty acid oxidation in peri-pubertal young rats. In this study, we measured fatty acid metabolism in the skeletal muscles and livers of 5 and 50 weeks old male and female rats. The rate of palmitate oxidation in the liver and gastrocnemius red in the 50-week-old female rats were elevated as compared to the 5-week-old females, whereas there were no differences in the male rats. The rate of palmitate oxidation in the gastrocnemius red was correlated inversely with intra-abdominal fat mass in the 5-week-old male and female rats, whereas the palmitate oxidation rate was positively correlated with fat mass in the liver and gastrocnemius red in the 50-week-old rats. HOMA-IR and plasma insulin levels were positively correlated with intra-abdominal fat mass in the pooled 50-week-old male and female rats, but this correlation was not apparent in 5-week-old rats. In summary, the rate of fatty acid oxidation measured in the middle-aged adult female rats was significantly higher than those measured in the peri-pubertal young female rats. This difference may be attributed to the influence of ovarian hormones.

• Journal of Sasang Constitutional Medicine
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• v.19 no.3
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• pp.242-256
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• 2007

1. Objectives Purpose of this study is to prove anti-aging and anti-oxidative effects of Gongjinhugwon-dan decoction. 2. Methods The SD rats used in this experiment were 6, 18, and 36 weeks old. Each age group was again divided into three groups. These nine groups consisted of 8 rats each. One group was given no treatment, another group was dosed $200{\mu}l$ of normal saline daily, and the last group was dosed $200{\mu}l$ of 1 % Gongjinhugwon-dan and saline mixture. At the conclusion of the experiment, the age groups were relabelled accordingly (10 weeks, 22 weeks, and 40 weeks). After 4 weeks, change of weight and liver markers were measured. Serum LDL cholesterol, total bilirubin, albumin, glucose, GOT and GPT levels were observed in order to check the hematological modification. Also, each organ tissue was biopsied in order to measure the SOD activity and the glutathione content change. 3. Results & Conclusions Aging did not cause any significant change in GOT and LDH, but GPT and albumin levels showed increase after GHD intake. Serum GPT was lower in the experimental group. Serum total bilirubin of the 40 w GHD group was significantly increased. The populations of dendritic cells in the spleens of the GHD groups were significantly increased. The levels of GSH in the liver of the 40 w GHD group and in the kidney of 22w-GSD were significantly increased in comparison with those of the normal groups. The degenerative change of brain tissue was decreased in the 40 w GHD group compared with those of the 40w normal group and the 40 w saline group. These results suggest that anti-oxidative GSH concentration of liver and kidney in rats treated with GHD showed significant increase in the 40 w GHD group. GHD was effective on increasing anti-oxidative substance in liver and dendritic cells in spleen, thus helping immune system and preventing cell mutation and degenerative change of brain tissues. Further studies and clinical investigation with GHD is needed.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.541-549
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• 2003

The present study investigated the effects of aging on Leydig cells of Sprague Dawley rats. Rats of 3, 6, 12 and 18 months of age were used. Testes of rat were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in epon-araldite. Using $1{\mu}m$ sections stained with methylene blue, qualitative and quantitative morphological studies were performed. Testis incubations were used to determine luteinizing hormone (LH; 100 ng/ml) stimulated testosterone secretory capacity per testis in vitro. Testosterone levels in the incubation medium, and testosterone and luteinizing hormone levels in serum of these four groups of rats were determined by radioimmunoassay. Morphological studies revealed that Leydig cells were more abundant in the testis interstitium at 6, 12 and 18 months when compared with 3 months. The volumes of Leydig cells per testis was significantly higher, at 6, 12 and 18 months of age than those at 3 months. The number of Leydig cells per testis was doubled at 6, 12 and 18 months of age compared with 3 months. The average volume of a Leydig cell was not significantly different between 3 and 6 months of age, however, at 12 and 18 months a significantly lower value was observed. LH-stimulated testosterone production per testis in vitro was reduced by 45% at 6 months of age compared with 3 months; a further significant reduction was observed at 12 and 18 months. Serum testosterone and LH levels were not significantly different between 3 and 6 months of age but at 12 and 18 months a significantly lower value was observed in both groups for these hormones. These results showed that signs of aging are apparent in Leydig cells of Sprague Dawley rats at 12 months of age.

• Applied Microscopy
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• v.25 no.4
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• pp.26-51
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• 1995

The present study was designed to examine effect of long term weight-training on aging atrophy in the rat skeletal muscle. Male rats of 8, 15, and 24 month old were used. Each age groups included control and weight-training for 5 months by using body press apparatus. The histo- and cytochemical, ultrastructural and stereological changes in aging skeletal muscles of the rat were observed in the present study. During the training period the body weight and muscular weight in all groups except the rectus femoris and the gastrocnemius in young age groups remained constant, but muscular weights were increased in the rectus femoris and the gastrocnemius muscles in young age groups. In trained rat, the volume density of muscle fiber type IIA and IIB were increased, but those of type IIC was decreased. Type I remained constant in 8 and 15 month old age groups, but reduced in the tibialis anterior and the gastrocnemius muscles in the 24 month old groups. Some histotological and ultrastructural changes associated with age were found: numerical increase of cytiplasmic vacuoles, lysosomes, lipofuscins, and irregularity of myofibrils. At 24 month old groups some unusual formation of contraction band and muscle splitting were observed. After weight-training, ultrastructural degenerative changes occured in the type I muscle fiber, such as splitting of muscle fiber, disorganization of myofilaments, swelling of mitochondria, accumulation of many lipid droplets, appearance of many lysosomes and residual bodies and necrotic fibers, in the old age groups. But, in the type II muscle fibers hypertrophy of muscle fiber appeared without any noticible damage as the type I. The activities of $Mg^{++}$ -ATPase decreased with age and this enzyme activities in the trained rat were significantly decreased with age. Activities of the acid phosphatase were increased with age and significantly in the trained rat. In stereological analysis, volume density of the myofibrils and the tubular system were increased, on the other hand there mitochondrial capacity was decreased. These experimental results suggested that old rats are not susceptible to be affected by weight-training as young rats, and that physical capacity of the rats must be considered when old rats are exercised for training.