scholarly journals Allopurinol Suppresses Azoxymethane-Induced Colorectal Tumorigenesis in C57BL/KsJ-db/db Mice

2020 ◽  
Vol 2 (4) ◽  
pp. 385-396
Author(s):  
Junichi Kato ◽  
Yohei Shirakami ◽  
Kimihiro Yamaguchi ◽  
Taku Mizutani ◽  
Takayasu Ideta ◽  
...  

Obesity and related metabolic disorders, including chronic inflammation and enhanced oxidative stress, are closely associated with the development and progression of colorectal cancer. Previous epidemiological studies have demonstrated that increased serum uric acid is associated with the risk for various types of cancer, including colon cancer. This study examined the effects of a xanthine oxidase inhibitor allopurinol, widely used as a uric acid lowering medicine, on colorectal tumorigenesis in obese mice. Male C57BL/KsJ-db/db mice were injected with azoxymethane (15 mg/kg body weight) and then received drinking water containing allopurinol (30 mg/kg body weight) for fourteen weeks. At the time of sacrifice, allopurinol treatment significantly inhibited the development of colonic premalignant lesions. In the allopurinol-treated group, cellular proliferation in colonic mucosa was significantly suppressed, which was evaluated by the expression of proliferating cell nuclear antigen. Allopurinol also inhibited macrophage infiltration in the adipose tissue and decreased the serum level of TNF-α. The values of oxidative stress markers were markedly decreased in the allopurinol-treated group compared to those in the control group. These findings suggest that allopurinol attenuated chronic inflammation and decreased oxidative stress, preventing the development of colonic pre-neoplastic lesions in obesity-associated colon tumorigenesis model.

2020 ◽  
Vol 31 (2) ◽  
pp. 106-109
Author(s):  
Oyedele Elliot Seyifunmi ◽  
Ayorinde Ajayi

AbstractIn this study, we attempt to verify the claim that the leaf-extract of Telfairia occidentalis can remedy oxidative damage condition as well as assess its phytochemical content. Fifteen male albino rats weighing 180 g to 240 g were randomly divided into three groups of five rats each. Group A was designated the control group while group B and C were both induced with 40 mg/kg body weight 2,4-dinitrophenyl hydrazine. Group C was subsequently treated with 200 mg/kg body weight of ethanol extract of T. occidentalis leaf for 21 days. At the end of the treatment, the animals were sacrificed, and serum of the samples were subjected to relevant tests. Result shows that the plant leaf contained saponin, tannins, alkaloids, flavonoids and phenols whereas, terpenes, steroids and anthraquinones were not detected. The serum enzymes alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly elevated from 17.43 u/L and 28.40 u/L to 21.60 u/L and 34.27 u/L respectively. These were significantly lowered in the group C to 18.37 u/L and 29.23 u/L respectively for ALT and ALP. Also, a significant lowering of superoxide dismutase (SOD) activity was observed in the treated group (54.33 u/mg) from 79.40 u/mg recorded in the intoxicated group. Similarly, a significant decrease in malondialdehyde was observed in the treated group (25.80 u/mg) relative to the intoxicated group (35.87 u/mg). Moreover, catalase activity in the treated group (7.43 u/mg) was significantly lower compared with the intoxicated group. Our observation confirmed that ethanolic leaf extract of T. occidentalis reversed the oxidative damage condition in albino rats. The result confirms the ethnomedicinal use of the plant in the management of oxidative stress related diseases.


Author(s):  
FATEN IBRAHIM EL-SAYED

Objective: The following study aimed to investigate the efficacy of curcumin at preventing amikacin neurotoxicity Methods: Twenty-four male Wister albino rats were randomly divided into four groups including-G (1): control group includes six rats, they were administered 0.5 ml of saline orally for 14 consecutive days. G (2): includes six rats; they were administered 200 mg/kg curcumin orally for 14 consecutive days. G (3): includes six rats, they were administered 300 mg/kg body weight/day of amikacin intraperitoneally for 14 consecutive days G (4): includes six rats, they were administered 200 mg/kg curcumin orally concurrently with 300 mg/kg body weight/day of amikacin. All animals were kept in the same conditions from feed, heat and humidity. Results: According to the result obtained after sacrification of all animals after the end of 14 d, Results revealed that amikacin at the dose rate of 300 mg/kg b. wt for 14 d induces significant changes in oxidative stress markers compared to the control group, a significant reduction in CAT. SOD. GSH (1.51±0.16, 77.00±0.73 and 84.06±4.42) respectively compared to control (3.63±0.11, 98.48±0.18 and 117.05±0.52) along with a significant increase in MDA activity (219.02±3.34) compared to control group (180.42±0.19), That indicate oxidative stress effect of it. On the beneficial side rats received amikacin 300 mg/kg B. wt I/p concurrently with 200 mg/kg b. wt curcumin for successive 14day result in a significant increase in CAT. SOD. GSH (2.23±0.09,92.00±0.26, 102.25±1.71) and decrease in MDA concentration (139.23±3.89) compared to amikacin treated group levels along with histopathological changes appear in brain tissue in the group treated with amikacin include nuclear pyknosis and degeneration in some neurons in the hippocampus, multiple focal eosinophilic plaque formation in the striatum also this results enhanced by activated caspase-3 expression in the brain tissue following amikacin administration. Conclusion: The present study proved that Oral administration of curcumin at the dose of 200 mg/kg for 14 d concurrently with amikacin significantly mitigates its neurotoxic and oxidative stress effects.


2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.


2021 ◽  
pp. 096032712110134
Author(s):  
O Zouaoui ◽  
K Adouni ◽  
A Jelled ◽  
A Thouri ◽  
A Ben Chrifa ◽  
...  

Phytochemical composition and antioxidant activity of flowers decoction at post-flowering stage (F3D) of Opuntia dejecta were determined. The obtained findings demonstrate that F3D has a marked antioxidant activity in all tested assays. Furthermore, the present study was designed to test the protective activity of F3D against induced Diabetes type 2 (DT2) in male rats. Those metabolic syndromes were induced by a high-fructose diet (HFD) (10% fructose solution) for a period of 20 weeks. F3D was administered orally (100 and 300 mg/kg body weight) daily for the last 4 weeks. Metformin (150 mg/kg body weight) was used as a standard drug and administrated orally for the last 4 weeks. The results showed a significant increase in blood glucose, triglycerides and hepatic markers (ALAT, ASAT and ALK-P) in HFD group. A significant increase in hepatic TBARS and a significant decrease in SOD, CAT and GPX were observed in fructose fed rats compared to control group. Administration of F3D showed a protective effect in biochemical and oxidative stress parameters measured in this study. Also, oral administration of F3D restored the histological architecture of rat liver in comparison with rats fed HFD. In conclusion, F3D attenuated hepatic oxidative stress in fructose-fed rats.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.


2016 ◽  
Vol 11 (1) ◽  
pp. 212 ◽  
Author(s):  
Saudy Saret Pablo-Pérez ◽  
María Mirian Estévez-Carmona ◽  
María Estela Meléndez-Camargo

<p class="Abstract">The aim of this study was to evaluate the diuretic activity of <em>Eysenhardtia polystachya</em> bark aqueous extract at different doses in a rat model. Different doses of <em>E. polystachya</em> (125, 250, 500 and 750 mg/kg body weight), furosemide (4 mg/kg) and vehicle were administered per os to female rats (n=6 animals per group). After 6 hours in metabolic cages, the effect on urinary flow, glomerular filtration rate and electrolyte balance of sodium and potassium were assessed in all animals. <em>E. polystachya</em> at the doses of 500 and 750 mg/kg induced diuretic activity, since markedly increased (p&lt;0.05) the urinary flow rate, similar to that of furosemide treated group. Only the dose of 750 mg/kg produced an increment in urinary excretion of sodium but not of potassium compared with control group. These findings indicate that<em> E. polystachya</em> bark-induced diuretic activity, providing evidence for its folkloric use.</p><p> </p>


2020 ◽  
Vol 20 (07) ◽  
pp. 16984-16996
Author(s):  
MMC Anyakudo ◽  
◽  
DO Adeniji ◽  

The metabolic response to nutrient ingestion and the rate of digestion and absorption of nutrient molecules in bowel physiology plays an important role in the metabolic control of some human chronic non-infectious diseases. This experimentally-controlled designed nutritional study which lasted eight weeks aimed to determine the effects of proportional high-protein/low-carbohydrate (HP/LC) formulated diet on glycemic tolerance, glycemic control, body weight, organ weight and organ morphometry in healthy and diabetic adult male Wistar rats. Twenty-four male Wistar rats purchased from a disease-free stock were randomly categorized into four groups (n = 6, each) after two weeks acclimatization period in raised stainless steel cages with 6 mm2mesh floor and replaceable numbered blotters papers placed under each cage in a well-ventilated animal house. Animal groups include: Healthy control group (HC), Healthy treated group (HT), Diabetic control group (DC) and Diabetic treated group (DT. The animals were fed according to the experimental design with water ad libitumfor eight weeks. Diabetes was inducted with freshly prepared alloxan monohydrate solution (150 mg/kg bw, intraperitoneally). Body weights and fasting blood sugar concentrations were measured twice weekly, while oral glucose tolerance test was conducted on the last day of the eighth-week study and subsequently followed by organs extraction after anesthesia for weight and gross assessment. Proportional high-protein/low-carbohydrate formulated diet caused significant reduction in mean body weight of treated diabetic (DT: 22.6%; P= .001) and healthy (HT: 5.8%; P= .007) rats while the control animals on control diet recorded significant (P< .05) increase in body weight gain (DC: 12.4%; HC: 11.2%). Glycemic tolerance and control improved significantly in diabetic treated rats over that of the healthy treated rats. Gross morphometry of the extracted organs (kidneys, liver, heart, lungs, spleen and testes) revealed sustained normal morphological features without any visible lesion. In conclusion, consumption of proportional high-protein/low-carbohydrate formulated diet enhanced body weight reduction and sustained normal organ morphological features with good glycemic tolerance and control in experimental rats, suggesting its dietary potentiality, safety and suitability to ameliorate obesity-related diabetes.


2021 ◽  
Vol 31 (3) ◽  
pp. 156
Author(s):  
Joko Wahyu Wibowo ◽  
Minidian Fasitasari ◽  
Siti Thomas Zulaikhah

<p>Oxidative stress is related to pregnancy complications that could increase maternal and infant mortality. This study aimed to determine the effect of propolis extract supplementation during pregnancy on oxidative stress level and pregnancy outcomes utilizing Malonedealdehyde (MDA) and 8-Oxo-2′-Deoxogunosine (8-OHdG) levels, maternal body weight, and the average number of fetuses as the parameters. The study was conducted by using a posttest only control group design on 24 pregnant Wistar rats, which were divided into four groups. Group I was control, Group II-IV were the treatment groups given propolis extract of 1.8mg, 3.6mg, and 7.2mg/200gBW/day, respectively. The standard feed given was AIN93G dose of 20g/day and distilled water ad libitum. Propolis extract was given using a gastric feeding tube every morning for 20 days. At the end of the treatment, body weight was meisured and blood collected for assessed MDA and 8-OHdG levels  by ELISA method  and then we performed abdominal surgery to count number of fetuses. The result are there were decreasing level of MDA and 8-OHDG by administration of propolis significantly (p&lt;0.05) group: I: 2,04±0,091, II: 1,55±0,067, III: 1,05±0,176, IV: 0,73±0,075 (mmol/mL) (p=0.001); 8 OHdG level (ng/mL) group I: 10,02±0,403, II: 8,60±0,078, III: 7,89±0,051, IV: 7,53±0,063 (p=0,001). Average of maternal body weight (g) were increased: group I: 228,33±3,93, II: 237,17±4,36, III: 244,83±4,02, IV: 248,00±5,76 (p=0,001) and Average number of fetuses tend to increased as well, group I : 8,5±0,05, II: 7,8±0,41, III: 9,5±1,05, IV: 9,6±0,52 (p=0,02). The conclusion of this research are supplementation of propolis extract in pregnant rats can reduce oxidative stress and improve pregnancy outcomes.</p>


Biomedicine ◽  
2020 ◽  
Vol 39 (2) ◽  
pp. 333-338
Author(s):  
Kalaivani Manokaran ◽  
Vasanthalaxmi Krishnananda Rao ◽  
Nilima . ◽  
Manjula Shimoga Durgoji Rao ◽  
Sucheta Prasanna Kumar

Introduction and Aim: Oxidative stress plays a very important role in endosulfan-induced toxic effects on reproductive organs. Vitamin C is a potent antioxidant which plays an important role in decreasing oxidative stress. The present study was aimed to investigate the protective role of vitamin C against endosulfan-induced testicular toxicity in Wistar rats. To investigate a protective effect of vitamin C against endosulfan induced toxicity on biochemical changes. Materials and Methods: Seventy male neonatal Wistar rats were divided into  seven groups. The group  I was taken as the control group, the endosulfan-treated were grouped into II (3 mg/kg body weight (BW) and group III (6 mg/kg BW), Group IV (9 mg/kg BW) and Group V (12 mg/kg BW). Group VI (9 mg/kg BW) and group VII (12 mg/kg BW) were pretreated with vitamin C (20 mg/kg BW) for 60 days. After  the experimental procedures, the testicular weight, lactate dehydrogenase (LDH) enzyme and testosterone in plasma, LDH, steroidogenic enzymes 3?-HSD and 17?-HSD in testis were evaluated. One-way ANOVA was used to determine the statistical significance. Results: Significant improvement in the testicular weight (P<0.05) , LDH (P<0.05) levels both in plasma and testis, increase in testosterone(P<0.001) and steroidogenic enzyme levels(P<0.001) was observed in the group pretreated with vitamin C treated group when compared to the endosulfan treated group. Conclusion: Vitamin C decreases the toxic effect of endosulfan on testis. The present action might be  due to its antioxidative properties.


2013 ◽  
Vol 3 (2) ◽  
pp. 65-70
Author(s):  
Sabah Ansar ◽  
Mohammad Iqbal ◽  
Noura Al Jameil

In this study the effect of butylated hydroxyanisole (BHA), a phenolic antioxidantused in food on Ferric‐Nitrilotriacetate (Fe–NTA) induced nephrotoxicity is reported. Fe‐NTA (9 mg Fe/kg body weight, intraperitoneally) treatment enhanced the renal microsomal lipid peroxidation and hydrogen peroxide generation to ~2‐2.5 folds compared to saline‐treated control and glutathione levels and the activities of antioxidant enzymes decreased to a range of 2–2.5 fold in kidney. These changes were reversed significantly in animals receiving a pretreatment of BHA. Pretreatment with BHA prior to Fe‐ NTA treatment reduced microsomal lipid peroxidation and hydrogen peroxide generation to 1.3‐1.5 fold compared to control group and glutathione and the activities of antioxidant enzymes increased to a range of 1.5‐2 folds in kidney. Fe‐NTA administration enhanced value of blood urea nitrogen and creatinine to 3.7 and 2.5 fold respectively as compared to their corresponding control group. Administration of Fe‐NTA to rats receiving a pretreatment of BHA led to a significant diminution in both of these values. The results indicate that BHA is a potent chemopreventive agent and suppresses Fe‐NTA induced nephrotoxicity in rats.


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