scholarly journals Liquiritigenin Protects Rats from Carbon Tetrachloride Induced Hepatic Injury through PGC-1αPathway

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yiping Zhang ◽  
Yuanqiao He ◽  
Hongbo Yu ◽  
Fuying Ma ◽  
Jianguo Wu ◽  
...  

The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas imposes serious challenges to the healthcare system. Here, we investigated the efficacy and mechanism of liquiritigenin involved in preventing or retarding the progression of liver diseases in a rat model with chronic carbon tetrachloride (CCl4) exposure. Sprague Dawley rats were given CCl4 and lliquiritigenin alone or simultaneously for 8 weeks before liver was harvested to check histological changes by Hematoxylin and Eosin (H&E) staining, apoptosis by TUNEL assay, ROS by dihydroethidium staining, antioxidant enzyme activities and malondialdehyde using specific kits, and gene expression by quantitative real-time PCR and western blot. Chronic CCl4 exposure caused profound changes in liver histology with extensive hepatocyte death (necrosis and apoptosis), fat accumulation, and infiltration of inflammatory cells, accompanied by depressed activities of antioxidant enzymes, increased oxidative stress, elevated expression of inflammation and fibrotic genes, and downregulation of PGC-1α, ND1, and Bcl-x in rat liver. All these changes were abolished or alleviated by lliquiritigenin. The results demonstrated that liquiritigenin is effective in protecting liver from injury or treating chronic liver diseases. The modulation of PGC-1αand its downstream genes might play a critical role in relieving CCl4-induced hepatic pathogenesis by liquiritigenin.

Author(s):  
S.D. Barnard ◽  
S.D. Warner

1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.


Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.


2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.


2015 ◽  
Vol 6 (3) ◽  
pp. ar.2015.6.0131 ◽  
Author(s):  
Nadieska Caballero ◽  
Kevin C. Welch ◽  
Patrick S. Carpenter ◽  
Swati Mehrotra ◽  
Tom F. O'Connell ◽  
...  

Background Several population studies demonstrated an increased risk of allergic rhinitis in patients exposed to acetaminophen. However, no histologic studies have been conducted to assess the relationship between acetaminophen exposure and allergic rhinitis. Objective In this study, we investigated the association between chronic acetaminophen exposure and the development of allergic rhinitis in a rat model. Methods Ten female Sprague-Dawley rats were randomly assigned to either a control (n = 5) or an acetaminophen group (n = 5). The acetaminophen group received 200 mg/kg/day of acetaminophen suspended in yogurt via oral gavage for 120 days. The control group received only the yogurt vehicle. Allergic behavioral responses, including nose rub, eye rub, ear scratching, and neck and/or face scratching, were quantified. The rats were killed, and the noses were harvested. The portion of the nose, including the nasal septum and the inferior turbinates, was embedded in paraffin, sectioned, and stained with hematoxylin and eosin to quantify the inflammatory infiltrate. Results The average number of allergic responses per animal was 13.2 in the acetaminophen group versus 6.2 in the control group (p = 0.032). All the rats in the acetaminophen group (100%) had mast cells infiltrating the lamina propria of the inferior turbinate, whereas mast cells were detected in only 40% of the animals in the control group. The average number of mast cells per animal in the acetaminophen group was 134 versus 21 in the control group (p = 0.048). Conclusions Our study was the first to demonstrate a histologic association between chronic exposure to acetaminophen and rhinitis. Further research to elucidate the mechanism that underlies these findings is necessary.


2006 ◽  
Vol 22 (3) ◽  
pp. 125-130 ◽  
Author(s):  
Mukaddes Gulec ◽  
Mustafa Iraz ◽  
H Ramazan Yilmaz ◽  
Huseyin Ozyurt ◽  
Ismail Temel

This study was carried out to determine if Ginkgo Biloba Extract (GBE or Egb 761) exerts a beneficial effect against cisplatin-induced renal failure in rats. Sprague Dawley rats were divided into four groups. The first group (control) received orally 1 mL/kg/day of 0.9% saline by an oral carrier vehicle on days 1 to 10. The second group was injected with 7 mg/kg cisplatin intraperitoneally (i.p.) on the fourth day, once only. The third group (vit E=cisplatin) was administered 10 mg/kg/day i.p. vit E on 1 to 10 days with one dose of i.p. cisplatin (7 mg/kg) injection on the fourth day. The fourth group (GBE=cisplatin) was given GBE orally at 100 mg/mL/kg started on the first day up to the tenth day with one dose of cisplatin (7 mg/kg) injection on the fourth day. Cisplatin was found to lead a statistically significant increase in plasma BUN and creatinine levels, as well as urine micro total protein (MTP) levels, leading to acute renal failure (ARF) in rats. Renal xanthine oxidase (XO) activities increased in all groups (statistically significant in cisplatin=GBE-treated rats; P≤0.001). Adenosine deaminase (AD) activities were increased in cisplatin-treated rats, and decreased in cisplatin=GBE-treated (PB≤0.041) and cisplatin=vit E-treated (PB≤0.005) rats, compared to controls. Malondialdehyde (MDA), nitric oxide (NO) levels and myeloperoxidase (MPO) activities were increased in the kidney tissue of cisplatin-treated rats. Vit E improved plasma creatinine and urine MTP levels, together with tissue MDA, NO levels, and MPO activities. But GBE had no statistically significant effect on those parameters. These results indicate that increased XO, AD and MPO activities, as well as MDA and NO levels play a critical role in cisplatin nephrotoxicity. GBE has been shown to protect against cisplatin-induced nephrotoxicity. Toxicology and Industrial Health 2006; 22: 125-130.


Urology ◽  
2003 ◽  
Vol 62 (2) ◽  
pp. 353-356 ◽  
Author(s):  
Feral Ozturk ◽  
Muharrem Ucar ◽  
I.Cetin Ozturk ◽  
Nigar Vardi ◽  
Kadir Batcioglu

2011 ◽  
Vol 125 (4) ◽  
pp. 370-375 ◽  
Author(s):  
V Kahya ◽  
A Meric ◽  
M Yazici ◽  
M Yuksel ◽  
A Midi ◽  
...  

AbstractObjective:To assess the effect of pomegranate extract on acute inflammation due to myringotomy.Design:Prospective, randomised study.Subjects:Thirty Sprague–Dawley rats were divided into three groups. Group one constituted controls. Group two underwent myringotomy. Group three underwent myringotomy and also received 100 µl/day pomegranate extract, via gavage, one day before and two days after surgery. Following sacrifice 48 hours after myringotomy, the animals' right ears were used to determine the concentration of reactive oxygen species, using the chemiluminescence method; left ears were used for histological study.Results:Reactive oxygen species levels were significantly decreased in group three compared with group two (p < 0.01). The density of inflammatory cells in group three was significantly less than that in group two (p < 0.01). Lamina propria thickness and vessel density were also significantly decreased in group three compared with group two (p < 0.01).Conclusion:Our results indicate that oral pomegranate extract decreases reactive oxygen species concentration and acute inflammation in the tympanic membrane after myringotomy.


2018 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Ari Estuningtyas ◽  
Santi Widiasari ◽  
Kusmardi Kusmardi

Objective: The plant mahkota dewa (Phaleria macrocarpa) is known to have anti-inflammatory effects. This study aimed to determine whetherchitosan nanoparticles containing mahkota dewa leaf extract would yield superior anti-inflammatory effects in the colon of a mouse model of dextransodium sulfate (DSS)-induced ulcerative colitis, compared with ethanol extract alone after testing the acute toxicities (lethal dose) of both preparations.Methods: For acute toxicity testing, 10 Sprague-Dawley rats were administered 6000 mg/kg body weight (BW) of leaf extract alone or with nanoparticles.Subsequently, mice were divided into the following six groups to determine the anti-inflammatory effects: Untreated, negative control (DSS 2% w/v), leafextract at 12.5 or 25 mg/kg BW, and leaf extract in chitosan nanoparticles at 6.25 or 12.5 mg/kg BW. To induce colitis, DSS (2% w/v) was administeredthrough drinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colonwith hematoxylin-eosin (HE) staining.Results: For acute toxicity testing, 10 Sprague-Dawley rats were administered 6000 mg/kg BW of leaf extract alone or with nanoparticles. Subsequently,mice were divided into the following six groups to determine the anti-inflammatory effects: Untreated, negative control (DSS 2% w/v), leaf extract at12.5 or 25 mg/kg BW, and leaf extract in chitosan nanoparticles at 6.25 or 12.5 mg/kg BW. To induce colitis, DSS (1% w/v) was administered throughdrinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colon withHE staining.Conclusion: Chitosan nanoparticles containing mahkota dewa leaf extract can be included in the practically non-toxic class of materials. However, anethanol extract of mahkota dewa leaf effectively inhibited DSS-induced inflammation in the mouse colon, regardless of delivery vehicle.


2018 ◽  
Vol 10 (1) ◽  
pp. 155
Author(s):  
Puspita Puspasari ◽  
Fadlina Chany Saputri

Objective: This study aimed to analyze the effect on wound healing following treatment with a water extract of Mirabilis jalapa L. by investigatingwound contraction and the associated histopathological changes in rat skin.Methods: Male Sprague-Dawley rats were divided into five groups, namely negative control, positive control (povidone-iodine), dose 1, dose 2, anddose 3. A 20-×10-mm rectangular wound area was created for the test. In dose 1, 2, and 3 groups, the corresponding dose variation of a 0.5-mLM. jalapa L. water extract (dose 1: 5% v/v, ≈243.1 mg/kg body weight BW; dose 2: 10% v/v, ≈486.2 mg/kg BW; and dose 3: 20% v/v, ≈972.4 mg/kg BW)was topically applied for 14 days on open wounds of rats. Widespread wound contractions were measured on days 1, 3, 5, 7, 9, 11, and 13, andhistopathological changes in the skin were observed on day 15 using hematoxylin and eosin staining.Results: The M. jalapa L. water extract accelerated wound healing. The optimal dose was found to be 20% v/v (≈972.4 mg/kg BW).Conclusion: M. jalapa L. extracts are potential healing agents for open wounds.


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