Discussion on rationality of administration of Angong Niuhuang Pills from pharmacological and toxicological perspectives

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Normal Control ◽  
Ischemia Reperfusion ◽  
Hematological Parameters ◽  
Scientific Basis ◽  
Neurological Function ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Toxicology Study ◽  
Body Weights

Abstract Background: Investigate the different treatment course of ANP from pharmacology and toxicology to provide scientific basis for clinic use. Method: In pharmacology study, cerebral ischemia-reperfusion model was made; rats were divided into six groups, Sham, model, aspirin 25 mg/kg, ANP 270 mg/kg (1 day, 4 days and 7 days) groups. Rats were fed for 30 days. Neurological function, cerebral infraction volume, brain histopathology, cytokines were detected; in toxicology study, rats were divided into four groups, normal control, ANP (550, 1640, 4910 mg/kg) group. ANP was daily administered by gavage for 30 days. Detection indicators included appearance, behavior, excrement character, food-intake, body weight, hematological parameters, etc. In addition, biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP were also detected. Result: In pharmacology study, compared with model group, the neurological function scores of ANP 270mg/kg (1 day, 4 days and 7 days) were decreased (P<0.11 or P<0.05); the volume of ANP 270mg/kg (1 day and 7 days) were decreased (P<0.05); the R value of ANP 270mg/kg (1 day, 4 days and 7 days) groups were decreased (P<0.11 or P<0.05); the serum content of IL-1β, TNFα and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P< 0.05); the brain content of IL-1β and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P<0.05). In toxicology study, no mortality, ophthalmic abnormalities were identified. Compared with normal control group, body weights were significantly lower in ANP 4910 mg/kg group; TBA was significantly increased in ANP 4910mg/kg group; liver organ coefficient of female rats of ANP 4910 mg/kg group was increased (P < 0.05); kidney organ coefficient of male rats of ANP 1640mg/kg, 4910 mg/kg groups were increased (P < 0.05), these all recovered after drug withdraw for 8 weeks. Conclusion: The effect of ANP 270 mg/kg (7 days) was much better than ANP (1 day and 4 days). ANP 550mg/kg is non toxicity dose. So, ANP is taken one pill peer day for 7 days is safety and effective, it can be used as the scientific basis for clinic use.

scholarly journals Effect of Chronic Administration of Aqueous Leaves Extract of Moringa Stenopetala on Blood Parameters and Histology of Liver and Kidney in Rats

2020 ◽  
Vol 30 (2) ◽  
Author(s):  
Fikre Bayu ◽  
Mekbeb Afework ◽  
Bekesho Geleta ◽  
Wondwossen Ergete ◽  
Eyasu Makonnen
Keyword(s):  
Hematological Parameters ◽  
Chronic Administration ◽  
Blood Parameters ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Histopathological Analysis ◽  
Moringa Stenopetala ◽  
Liver And Kidney ◽  
Hematological And Biochemical Parameters

BACKGROUND: Moringa stenopetala is used as nourishments, and treatment of various diseases. However, there is no much information on its safety. Hence, this study aimed to investigate the chronic administration of aqueous leaves extract of the plant.MATERIALS AND METHODS: Twenty-four rats were divided into: a control group administered with distilled water and three experimental groups, respectively, administered with the extract at doses of 500, 1000, and 2000 mg/kg orally for six months were investigated. Various hematological and biochemical parameters followed by histopathological analysis were evaluated.RESULTS: Treatment with the extract did not significantly affect most of the hematological parameters. However, there were a significant decrease of MCH at doses of 1000 mg/kg and 2000 mg/kg in male rats and increase of MCV at all doses in female rats. Levels of ALP at 2000 mg/kg and those of AST and ALT at 1000 and 2000 mg/kg were significantly increased in male rats. Furthermore, significant decrease in urea and increase in creatinine levels at the dose of 2000 mg/kg occurred in female rats. Mild histopathological changes were also observed in the liver of male rats and kidney of female rats treated with the extract, respectively at doses of 1000 and 2000 mg/kg, and 2000 mg/kg.CONCLUSION: Findings from the present study suggest that prolonged administration of extract of Moringa stenopetala at therapeutic doses is safe, but shows sign of mild toxicity as dose increases, with differential effect on male verses female rats.

scholarly journals The Preventive Effects of Diminazene Aceturate in Renal Ischemia/Reperfusion Injury in Male and Female Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maryam Malek ◽  
Mehdi Nematbakhsh
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Female Rats ◽  
Male Rats ◽  
Converting Enzyme ◽  
Diminazene Aceturate ◽  
Male And Female ◽  
Male And Female Rats

Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats.Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n=6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group.Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P<0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P<0.05).Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level.

Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murtala Akanji Abdullahi ◽  
Elijah Oladapo Oyinloye ◽  
Akinyinka Alabi ◽  
Aderonke Adeyinka Aderinola ◽  
Luqman Opeyemi Ogunjimi ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Density Lipoprotein ◽  
Serum Testosterone ◽  
Female Rats ◽  
Male Rats ◽  
Laboratory Animals ◽  
Serum Testosterone Level ◽  
Control Group ◽  
Toxicological Evaluation ◽  
Liver And Kidney

Abstract Objectives Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. Methods Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. Results The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. Conclusions The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.

scholarly journals Subchronic toxicity of aqueous extract of Alstonia boonei de wild. (apocynaceae) stem bark in normal rats

2015 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Barnabé Lucien Nkono Ya Nkono ◽  
Selestin Dongmo Sokeng ◽  
Paul Désiré Dzeufiet Djomeni ◽  
Frida Longo ◽  
Pierre Kamtchouing
Keyword(s):  
Aqueous Extract ◽  
Biochemical Study ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Control Male ◽  
Control Female ◽  
Hematological Analysis ◽  
Wbc Count ◽  
Dose Dependent

<p><strong>Methodology:</strong> Wistar rats were randomly assigned into eight groups of five animals each: four male groups and four female groups. Each sex group had a control group receiving distilled water and three test groups receiving 200, 500 and 1000mg/kg respectively. Animal’s body weights were recorded on the first day and once a week for the four experiment weeks. The hematological analysis included total WBC count, total RBC count, Hb, %HCT, MCV, MCH and MCHC. Biochemical/serum profile studies include TG, TC, ALT, AST, urea and TP. Tissue specimens of the liver, kidney and lung were subjected to histological examination using standard hematoxylin-eosin staining.</p><p><strong>Results:</strong> In male rats, aqueous extract showed significant decreases in relative weight of liver with extreme significance P&lt;0.001 at a dose of 200mg/kg (vs. control group), P&lt;0.001 of lung at all the doses, P&lt;0.05 (200 and 500mg/kg) and P&lt;0.01 (1000mg/kg) in heart weight. In relative kidney weight, only the dose of 1000mg/kg showed a significant increase vs. normal control male rats. Unlike male rats, only relative kidney weight in female rats was significantly different from the control group in a dose-dependent manner. The aqueous extract treated male groups showed significant increases P&lt;0.001 (1000mg/kg) of total WBC count and MCHC, significant decreases of %HTC (dose response manner), P&lt;0.05 total RBC count (at doses of 500 and 1000mg/kg) and Hb P&lt;0.01 (500mg/kg) vs. normal male rats. In female rats, the haematological study showed significant increase P&lt;0.01 of total WBC count (at the doses of 500 and 1000mg/kg), significant decreases P&lt;0.05 and P&lt;0.01 of total RBC respectively at the doses of 200 and 1000mg/kg, significant decrease of Hb with extreme significance P&lt;0.001 at the dose 1000mg/kg, %HTC also decrease dose response manner vs. control female rats. Biochemical study showed in male rats significant decreases in level of TG P&lt;0.001 (at the doses of 200 and 500mg/kg) and urea, although it showed any dose-dependent effect vs. control male rats. AST also decreases (P&lt;0.05) in male rats at the dose of 200mg/kg but significantly increase P&lt;0.001 at the dose of 500mg/kg. In the female rats, biochemical study revealed significant increases in level of TG P&lt;0.001 and urea P&lt;0.01 at the dose of 200mg/kg and significant decreases in level of TG P&lt;0.01, AST P&lt;0.05 and urea P&lt;0.05 at the dose of 500mg/kg (vs. control female rats). Microscopically, there were mild hepatic and renal tissue injuries supporting the hematological analysis.</p><p><strong>Conclusion:</strong> The results indicated that aqueous extract of <em>Alstonia boonei</em> De Wild is toxic in high doses.</p>

scholarly journals Catalase activity as signal of antioxydant system affection under influence of limb ischemia-reperfusion

2021 ◽  
pp. 24-30
Author(s):  
Nataliya Volotovska
Keyword(s):  
Risk Factors ◽  
Blood Loss ◽  
Catalase Activity ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Mechanical Injury ◽  
Male Rats ◽  
Mechanical Trauma ◽  
Control Group ◽  
Ischemic Reperfusion

The use of hemostatic tourniquet is a proved means of primary care. However, systemic disorders, as well as ultrastructural, in the area of compression can significantly worsen the condition of the injured organism. The aim. Estimation of catalase level in rats’ liver on the background of modifications of ischemic-reperfusion syndrome to know the severest pathogenic combination for organism. Materials and methods. 260 white adult male rats were divided into 5 groups: control (KG), EG1 – simulation of isolated ischemia-reperfusion syndrome (IRS) of the limb, EG2 – simulation of isolated volumetric blood loss, EG3 – combination of IRS of the limb with blood loss, EG4 – simulation of isolated mechanical injury of the thigh, EG5 – combination of IRS of the limb and mechanical injury. The variability of catalase level in liver was analyzed. Results. It was found that each of the experimental interventions has led to changes of catalase activity in the liver. The most expressed pathological expressions were observed on the 3rd after interventions, when the studied index in EG3 was lower than in EG1 and EG2 in 6,2 times and by 33,1 %. On the 7th day catalase activity in EG3 was in 9,4 times and by 44,5 % times lower than in EG1 and in EG2 data concordantly. The combination of limb ischemia-reperfusion with blood loss in EG3 led to exhausting of liver antioxydant enzyme catalase in the most critical posttraumatic period (day 3). The same, but less significant effect was registered in the group of combination of mechanical trauma with ischemia-reperfusion in EG5. This proved the role of the tourniquet as a factor that complicated the course of traumatic disease due to ischemic reperfusion. Conclusions. In this experiment, founded risk factors of combination of ischemia-reperfusion with heavy blood loss emphasized the importance and particular attention on such widespread method of bleeding tratment, as the imposition of a tourniquet, as in our experiment it triggered risk factors of ischemia-reperfusion. It was shown katalase activity depression respectively to the periods of increasing of lipid peroxydation. There was peculiarity, that on the base of isolated IRS catalase activity was increased in 2,5 times comparely to control group, whereas the hardest depression of it was found on the background of IRS, combined with blood loss – catalase activity was lower, comparely to KG – in 2,5 times. The importance of understanding the suppression of hepatocytes’ antyoxydants is great, as it might help in prevention the development of liver failure or hepatorenal syndrome on the background of limb ischemia-reperfusion.

Acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii (Miq.) Miq. stem bark in rats

2021 ◽  
Vol 10 (2) ◽  
pp. 89-97
Author(s):  
EL Lappa ◽  
◽  
C Bogning Zangueu ◽  
EL Nguemfo ◽  
JJ Kojom Wanche ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Chronic Toxicity ◽  
Hematological Parameters ◽  
Lethal Dose ◽  
Relative Weight ◽  
Stem Bark ◽  
The Body ◽  
Female Rats ◽  
Male Rats

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.

Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Body Weight ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Toxic Effect ◽  
Treatment Period ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
The Body ◽  
Therapeutic Effects ◽  
Toxicology Study

Abstract Background : Angong Niuhuang Pill (ANP) is one of the most famous drugs to treat stroke in China, but there is no definite treatment period in drug instruction. In this study, we used middle cerebral artery occlusion (MCAO) model to evaluate its therapeutic effects of different treatment periods and studied its toxic effect in rats. Methods : Protective effect of ANP was observed in the cerebral ischemia-reperfusion model in rats; ANP (270 mg/kg) three different treatment period included 1 day, 4 days and 7 days. The observation period was 30 days. Therapeutic effect was evaluated by detecting neurological function, cerebral infraction volume, brain histology and cytokines. Three dose including 550, 1640, 4910 mg/kg were studied in toxicology study. The administration period was 30 days. Toxic effect was evaluated by detecting appearance, behavior, excrement character, food-intake, body weight, hematological parameters and biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP. Results : Seven days treatment period of ANP had better effect than 1 day and 4 days treatment periods in rat MCAO model from neurological function scores, the volume of cerebral infarction, brain histology and the serum content of IL-1β, TNF-α and NO; the brain content of IL-1β and NO. The results of 30 days multiple dose toxicology study showed no animal death in all groups; in ANP 4910 mg/kg group, the kidney and liver coefficient increased about 10%, the body weight grew more slowly, the TBA increased slightly. There was no abnormal change in histology. These all recovered after drug withdraw for 8 weeks. Conclusion: Seven days treatment period of ANP had more protective effect than 1 day and 4 days treatment periods in ischemic stroke rat. No observed adverse effect level (NOAEL) of ANP was 1640 mg/kg; the safety margin of ANP was 270-1640 mg/kg. These data provided reference to modify drug instruction.

Influence of in utero di-n-hexyl phthalate and di-cyclohexyl phthalate exposure on the endocrine glands and T3, T4, and TSH hormone levels of male and female rats: Postnatal outcomes

2020 ◽  
Vol 36 (6) ◽  
pp. 399-416
Author(s):  
Nurhayat Barlas ◽  
Emre Göktekin ◽  
Gözde Karabulut
Keyword(s):  
Pituitary Gland ◽  
Dose Group ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Hormone Levels ◽  
Male And Female Rats ◽  
Endocrine Organs ◽  
Body Weights ◽  
Juvenile Stages

The present study was designed to evaluate the effects of di- n-hexyl phthalate (DHP) and di-cyclohexyl phthalate (DCHP) on endocrine organs in rats. Oil control, 20-, 100-, and 500 mg/kg dose groups were selected and administered to pregnant rats on gestational days 6–19 by oral gavage. The neonatal stages of rats continued until postnatal day 20 and the- juvenile stages of rats continued until postnatal day of 32. The rats were allowed to mature until the neonatal and juvenile stages and there after, they were divided into four groups corresponding to the treatment levels. Body and organ weights were recorded, serum was collected, and thyroid, pancreas, pituitary gland, and adrenal gland were removed. There was a decrease in body weights in the 20- and 500mg/kg DHP and in the 20-mg/kg DCHP dose groups in neonatal male rats. In contrast, for female rats, there was an increase in body weights in the 100-mg/kg DCHP dose group and there was a decrease in body weights in the 500-mg/kg DHP dose group. Body weights were increased at 20 and 500 mg/kg in the DHP-exposed juvenile male rats. Serum thyroid-stimulating hormone (TSH) levels were increased in neonatal male rats, while they were increased in the 100-mg/kg DHP group of neonatal and juvenile female rats. Serum triiodothyronine (T3) levels were increased at the high dose of DHP for neonatal male rats and at the low and high dose levels of DCHP for female rats. Serum thyroxine (T4) levels were increased in neonatal rats for DHP. Also, some histopathological changes were observed in the thyroid, pancreas, adrenal, and pituitary gland. In conclusion, it was shown that DHP and DCHP caused negative effects on T3, T4, and TSH hormone levels.

A Teratological Evaluation and Postnatal Behavioral Screen of KF-868 In Rats

1985 ◽  
Vol 4 (1) ◽  
pp. 91-110 ◽  
Author(s):  
A. M. Hoberman ◽  
W. M. Weatherholtz ◽  
R. S. Durloo
Keyword(s):  
Body Weight ◽  
Vehicle Control ◽  
Female Rats ◽  
Reproductive Capacity ◽  
Control Group ◽  
Dosage Group ◽  
Vehicle Control Group ◽  
High Dosage Group ◽  
Significant Difference ◽  
Body Weights

The effects of a new experimental drug, KF-868, were investigated after administration to pregnant Sprague-Dawley rats at 0(vehicle), 0.1, 2.0, and 40.0 mg/kg per day during Days 7 through 17 of gestation by examination of term fetuses and naturally delivered offspring. Pregnant rats administered 0.1, 2.0, and 40.0 mg/kg per day gained significantly more weight during the dosage period than did the vehicle control group. Treatment-related physical signs, bloody crust on nose and stains on fur, were observed in the high dosage group. Fetal viability was significantly increased, and resorptions were significantly decreased for the mid and high dosage groups, when compared with the control group. Average fetal body weights for cesarean-delivered fetuses were less for the 40.0 mg/kg per day dosage groups than for the vehicle control group. Visceral and skeletal evaluations of fetuses revealed no difference between the control and test groups. Percent survival of pups was significantly less for the high dosage group than for the control group. Average rat body weights prior to mating for the high dosage group were generally less than for the control group. All physical and functional developmental values were comparable among the control and test groups. Evaluation of postweaning parameters of pups revealed no significant difference in sex maturation, behavior (open-field and water maze), and reproductive capacity. Average body weight gains during the 9-week growth period before mating were significantly less for the 40.0 mg/kg per day dosage group F1 generation female rats. Toxicity in fetuses and offspring was observed only at the highest dosage level. Dosage-dependent, significant increases in maternal body weight gain, as compared with control values, occurred for doses in the 3 KF-868-administered groups. These results indicate that 0.1 and 2.0 mg/kg per day dosages of KF-868 were not lethal and did not produce any adverse effects on the morphological or functional development of offspring. Toxicity was evident in offspring and fetuses of dams administered 40.0 mg/kg per day KF-868, 40,000 times as high as the daily therapeutic dose.

scholarly journals Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongzhong Liu ◽  
Xingjian Zhang ◽  
Qi Xiao ◽  
Shaojun Ye ◽  
Chin-Hui Lai ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Control Group ◽  
Isolated Perfused Rat Liver ◽  
Enzyme Release ◽  
Circulatory Death ◽  
Dependent Mechanism

Objective. Severe hepatic ischemia reperfusion injury (IRI) can result in poor short- and long-term graft outcome after transplantation. The way to improve the viability of livers from donors after circulatory death (DCD) is currently limited. The aim of the present study was to explore the protective effect of simvastatin on DCD livers and investigate the underlying mechanism. Methods. 24 male rats randomly received simvastatin or its vehicle. 30 min later, rat livers were exposed to warm ischemia in situ for 30 min. Livers were removed and cold-stored in UW solution for 24 h, subsequently reperfused for 60 min with an isolated perfused rat liver system. Liver injury was evaluated during and after warm reperfusion. Results. Pretreatment of DCD donors with simvastatin significantly decreased IRI liver enzyme release, increased bile output and ATP, and ameliorated hepatic pathological changes. Simvastatin maintained the expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced oxidative stress, inhibited innate immune responses and inflammation, and increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared to DCD control group. Conclusion. Pretreatment of DCD donors with simvastatin improves DCD livers’ functional recovery probably through a KLF2-dependent mechanism. These data suggest that simvastatin may provide a potential benefit for clinical DCD liver transplantation.

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