Effect of You-Gui Yin on the Activities of Seven Cytochrome P450 Isozymes in Rats

You-Gui Yin (YGY) is a traditional Chinese medicine (TCM) decoction composed of eight Chinese herbs. The interaction between TCM and Western medicine has attracted much attention nowadays. It is therefore necessary to study the clinical application of YGY in combination with Western medicine from the perspective of metabolic enzymes. This study aims to investigate the effect of YGY on the activities of seven CYP450 isozymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) in rats. Twenty-four Sprague-Dawley (SD) rats were randomly divided into four groups: high, middle, and low-dose YGY-treated groups and the control group. They were given 13.78, 20.67, and 31 g/kg/d YGY decoction by oral administration and normal saline (10 mL/kg), respectively, for 14 days. Half an hour after the last administration, a mixed probe substrate (1 mg/kg) was administered by tail vein injection. Then, blood was taken from the venous plexus at different time points. The protein expression level of the CYP450 enzymes in the control and treatment groups was determined by western blot. The effect of YGY on the activity of CYP isoenzymes was studied by comparing the plasma pharmacokinetics between the control and treatment groups. Compared with the control group, YGY at a high (31 g/kg) dosage could decrease AUC(0–t), AUC(0–∞) and Cmax of diclofenac, omeprazole, and midazolam by at least 35.4%, while increase CL by at least 88.9%; this revealed that YGY could induce CYP2C9, CYP2C19, and CYP3A4. The results show that when we use You-Gui Yin decoction in combination with other drugs, especially drugs metabolized by CYP2C9, CYP2C19, and CYP3A4 enzymes, the interaction between drugs needs special attention.

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Does Human Amnion Membrane Prevent Postoperative Abdominal Adhesions?

The American Surgeon ◽

10.1177/0003134820939939 ◽

2020 ◽

Vol 86 (8) ◽

pp. 1038-1042

Author(s):

Hannah M. Nemec ◽

Hany Atalah ◽

Melissa Kling ◽

Larry Nichols ◽

Bowen Powers ◽

...

Keyword(s):

Abdominal Surgery ◽

Statistical Significance ◽

Adhesion Formation ◽

Scar Tissue ◽

Control Group ◽

Sprague Dawley ◽

Ongoing Research ◽

Human Amnion ◽

Treatment Groups ◽

Tissue Matrix

Background Adhesions are bands of tissue that form postoperatively after intra-abdominal surgery. Adhesions cause significant morbidity and despite ongoing research no agent or method has been shown to completely prevent adhesions. Human amnion-derived matrix is a complex tissue matrix derived from human placenta and has been used in other areas of surgery to promote healing and decrease scar tissue formation. Our hypothesis was that aerosolized human amnion-derived matrix particulate solution (HAMPS) applied during abdominal surgery would decrease adhesion formation in rats. Methods Twenty-four Sprague-Dawley rats were divided into 4 different groups. Group 1 was the control group (CG) which had cecal abrasion 20× with a surgical rasp to generate the adhesion model. Groups 2-4 were the treatment groups (TGs) and had cecal abrasion plus application of the HAMPS at concentrations of 6.25, 12.5, and 25 mg/cc, respectively. After 30 days, rats were euthanized and adhesion assessment performed. Results In all groups there were minimal adhesions noted at necropsy. Moderate inflammation was 33% in CG versus 11% in combined TGs. Average adhesion was 1.00 in CG versus 0.44 in combined TGs. This indicated an observational improvement in adhesions/inflammation in the TGs, although this did not reach statistical significance. There was a trend toward significance in the 12.5 mg/cc group alone ( P = .054). Conclusion Overall, HAMPS showed an observational decrease in adhesions in TGs although not statistically significant. There was a trend toward significance in the 12.5 mg group. Additional studies will have to be performed to further evaluate this subgroup.

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Sustained Tau Phosphorylation and Microglial Activation Following Repetitive Traumatic Brain Injury

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.5471 ◽

2020 ◽

Vol 8 (A) ◽

pp. 837-840

Author(s):

Andre Marolop Pangihutan Siahaan ◽

Rr Suzy Indharty ◽

Jessy Chrestella ◽

Wismaji Sadewo ◽

Steven Tandean ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Treatment Group ◽

Microglial Activation ◽

Control Group ◽

Sprague Dawley ◽

Sham Control ◽

Treatment Groups ◽

Sham Control Group ◽

Cd 68

BACKGROUND: Repetitive traumatic brain injury (TBI), even without acute sequela, can induce a delayed neurodegenerative with overexpression of phosphorylated tau (p-tau) as hallmark, caused by chronic inflammation mediated in part by microglial activation. AIM: The aim of this study was to examine the dynamics of p-tau accumulation and microglial activation following repetitive TBI. MATERIALS AND METHODS: Thirty Sprague–Dawley rats were randomized into a sham control group and two treatment groups receiving three successive closed-skull impacts (TBI model) from a 40-g mass dropped from a 1-m height on alternating days (days 0, 1, 3, and 7). The first treatment group was sacrificed on the last day of trauma and the second treatment group after 7 days of no trauma. The expression level of p-tau was evaluated by AT-8 antibody immunostaining and microglial activation by anti-CD-68 immunostaining. RESULTS: Immunoexpression of AT-8 was significantly elevated 7 days after TBI compared to the last day of trauma and compared to the sham control group, while CD-68 expression was significantly higher than sham controls on the last day of trauma and remained elevated for 7 days without trauma. CONCLUSION: The study showed that brain trauma can induce p-tau overexpression and microglial activation that is sustained during the non-trauma period.

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The Effect of a Synthetic Heparan Sulfate on the Healing of Colonic Anastomoses

Gastroenterology Research and Practice ◽

10.1155/2017/1078062 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6

Author(s):

Malene Nerstrøm ◽

Peter-Martin Krarup ◽

Lars Nannestad Jorgensen ◽

Magnus S. Ågren

Keyword(s):

Tissue Repair ◽

Single Layer ◽

Control Group ◽

Sprague Dawley ◽

Colonic Anastomoses ◽

Treatment Groups ◽

Sprague Dawley Rats ◽

Heparan Sulfates ◽

Biomechanical Strength ◽

Mimetic Compound

Background. The mimetic compound OTR4120 may replace endogenous-degraded heparan sulfates that normally maintain the bioactivity of growth factors that are important for tissue repair. Herein, we investigated the effect of OTR4120 on the healing of normal colonic anastomoses. Methods. We evaluated the following two treatment groups of male Sprague Dawley rats (220–256 g): control-treated colonic anastomoses (n=25) and OTR4120-treated colonic anastomoses (n=25). We resected 10 mm of the left colon and then applied either saline alone (control) or OTR4120 (100 μg/mL) in saline to the colonic ends before an end-to-end single-layer anastomosis was constructed and again on the anastomosis before the abdomen and skin were closed. Results. On postoperative day 3, the anastomotic breaking strengths were 1.47 ± 0.32 N (mean ± SD) in the control group and 1.52 ± 0.27 N in the OTR4120-treated animals (P=0.622). We also found that the hydroxyproline concentration (indicator of collagen) in the anastomotic wounds did not differ (P=0.571) between the two groups. Conclusions. Our data demonstrate that a single local application of OTR4120 intraoperatively did not increase the biomechanical strength of colonic anastomoses at the critical postoperative day 3 when the anastomoses are the weakest.

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THE HIGH DOSE TOXICITY OF BETEL NUT (Areca catechu L.) ON REPRODUCTION ORGAN OF RATS

JAMBI MEDICAL JOURNAL Jurnal Kedokteran dan Kesehatan ◽

10.22437/jmj.v7i1.7059 ◽

2019 ◽

Vol 7 (1) ◽

pp. 41-49

Author(s):

Ave Olivia Rahman ◽

Herlambang Herlambang ◽

Charles A Simanjuntak ◽

Hasna Dewi ◽

Ahmad Syauqy ◽

...

Keyword(s):

Rattus Norvegicus ◽

Histopathological Examination ◽

Herbal Medicines ◽

Reproductive Organs ◽

Control Group ◽

High Dose ◽

Betel Nut ◽

Sprague Dawley ◽

Treatment Groups ◽

Areca Catechu

ABSTRACT Background : The use of long-term herbal medicines and high doses can damage organs, including the reproductive organs. Betel nut (Areca catechu L.) is one of the herbal ingredients that is consumed as a stamina enhancing beverage. The purpose of this study was to determine the effect of longterm treatment of raw betel nut at a dose of 10,000 mg/kg on testicular and ovary tissue of rats. Rats were Rattus norvegicus, Sprague Dawley strain, 2-3 months. Methods : Tweenty rats divided into 2 groups, each groups were 5 male and 5 female. Control group was given aquades and the treatment group was given raw betel nut with a dose of 10,000 mg/kgBW for 45 days with a gastrictube. Histopathological examination with Haematoxylin-Eosin staining was used to assses testicular and ovary tissues. Results: The ovaries of treatment groups had significantly lower de graff follicle compared to the control group (p < 0,05). The testis of treatment groups had significantly smaller diameter of tubulus seminifery, significantly higher necrosis of spermatogonia and spermatosit (p<0,05). Conclusion: Treatment of raw betel nut dose 10,000 mg /kgBW along 45 days causes damage of testicular and ovary tissues of rats.Keywords: Betel Nut, Areca Catechu L., Histopathology, Testicular, Ovary, Herbal Toxicity ABSTRAK Latar Belakang: Pemakaian obat herbal jangka panjang dan dosis tinggi dapat menyebabkan kerusakan organ tubuh, termasuk organ reproduksi. Biji pinang (Areca catechu L.) merupakan salah satu bahan herbal yang dikonsumsi sebagai minuman penambah stamina.Tujuan penelitian ini adalah untuk mengetahui pengaruh pemberian biji pinang muda dosis 10.000 mg/ kgBB selama 45 hari terhadap gambaran histopatologis testis dan ovarium tikus. Metode : Tikus yang digunakan adalah Rattus norvegicus galur Spague Dawley, usia 2-3 bulan, sebanyak 10 ekor jantan dan 10 ekor betina yang dibagi menjadi 2 kelompok, yaitu kelompok kontrol diberikan aquades dan kelompok perlakuan diberikan biji pinang dosis 10.000 mg/ kgBB dengan sonde. Pemeriksaan histopatologi dengan pewarnaan Haematoxylin-Eosin untuk organ testis dan organ ovarium. Hasil: Jumlah folikel de draf pada kelompok perlakuan lebih sedikit dibandingkan kelompok kontrol (p<0,05). Persentase nekrosis spermatogonia dan spermatosit pada kelompok perlakuan lebih tinggi dibandingkan kelompok kontrol (p<0,05), diameter tubulus seminifeus pada kelompok perlakuan juga lebih kecil dibandingkan kelompok kontrol (p<0,05). Kesimpulan: Pemberian biji pinang 10.000 mg/kgBB selama 45 hari menyebabkan kerusakan pada jaringan testis dan ovarium pada tikus. Kata Kunci : Biji Pinang, Areca Catechu L, Histopatologi, Ovarium, Testis, Toksisitas herbal

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Evaluation of the contraceptive effects of carprofen, flunixin meglumine and meloxicam in rats

Veterinární Medicína ◽

10.17221/67/2016-vetmed ◽

2017 ◽

Vol 62 (No. 5) ◽

pp. 274-278

Author(s):

Z. Paksoy ◽

A. Kirbas

Keyword(s):

Single Dose ◽

Implantation Rate ◽

Control Group ◽

Double Dose ◽

Sprague Dawley ◽

Dose Administration ◽

Treatment Groups ◽

Flunixin Meglumine ◽

Sprague Dawley Rats ◽

Implantation Sites

The objective of this study was to determine the suitability of carprofen, flunixin meglumine and meloxicam for use in emergency contraception. Forty-eight pregnant Sprague-Dawley rats were used as material. Five groups were subjected to treatments while one group served as a control. The numbers of animals in each group were equal (n = 8). Treatment groups were administered carprofen (10 mg/kg, single or double dose, s.c.), flunixin meglumine (5 mg/kg, single or double dose, i.m.) and meloxicam (2 mg/kg, a single dose, s.c.) on the third day after mating. The control group received saline. The rats were sacrificed on Day 7 of gestation. Luteal spots and implantation sites were recorded. Pre-implantation loss was calculated by subtracting the number of luteal spots from the number of implantation sites. Compared with the control, the administration of flunixin meglumine (double dose), carprofen (double dose) and meloxicam highly significantly decreased the implantation rate (P < 0.001). Single dose administration of flunixin meglumine and carprofen led to significant decreases (P < 0.01). In conclusion, this study indicates that carprofen, flunixin meglumine and meloxicam treatment cause a decline in implantation rate in rats.

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Feeding Sprague Dawley Rats With Jordanian Wild Edible Plants and a High Fat Diet Reduced the Malondialdehyde Levels

Journal of Agricultural Science ◽

10.5539/jas.v11n10p71 ◽

2019 ◽

Vol 11 (10) ◽

pp. 71

Author(s):

Anwar A. Al-Assaff ◽

Hamed R. Takruri

Keyword(s):

High Fat Diet ◽

Fasting Blood Glucose ◽

Serum Levels ◽

The Other ◽

Control Group ◽

Sprague Dawley ◽

High Fat ◽

Treatment Groups ◽

Sprague Dawley Rats ◽

Plant Powders

The objective of this study was to determine the effect of selected Jordanian wild edible plant on lipid peroxidation and lipid profile in adult male Sprague Dawley rats fed high-fat diet. Fiftysix male, adult Sprague-Dawley rats at eight weeks of age, weighing about 200g were distributed into 7 experimental groups, 7 rats each . The groups included a negative control group that was fed a normal fat diet (NFD) and a possitve control group that was fed a high fat diet (HFD) (45% calories from fat). The six treatment groups were fed a HFD for the first 4 weeks of the experiment and a HFD with 9% of one of the selected dried plants for another 4 weeks. The treatment groups are sumac, thyme, clary, gundelia, garden rocket and wild mint. Blood samples were collected from the right heart ventricle. Serum malondialdehyde, lipid profile and fasting blood glucose were measured for rats. Results showed that the addition of different dried plant powders to the HFD did not significantly affect serum levels of TG, TC, HDL, LDL and fasting blood glucose. On the other hand, malondialdehyde (MDA) levels were significantly (p < 0.05) higher in the HFD group (4.09±0.45 mmol/ml) than those of other groups. MDA serum levels for the other groups were as follows: NFD (2.47±0.05), sumac (2.45±0.13), thyme (2.88±0.07), clary (2.97±0.16), garden rocket (2.96±0.11), gundelia (2.92±0.16) and wild mint (2.68±0.09). These levels were not sinificantly different from each other. It is concluded that incorporating dried plant powders in rat diets had a significantly positive effect only on lipid peroxidation assay as indicated by serum MDA levels.

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Turmeric Extract Supplementation Reduces Tau Protein Level in Repetitive Traumatic Brain Injury Model

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.440 ◽

2018 ◽

Vol 6 (11) ◽

pp. 1953-1958

Author(s):

Andre Marolop Pangihutan Siahaan ◽

Iskandar Japardi ◽

Aldy Rambe ◽

Rr Suzy Indharty ◽

Muhammad Ichwan

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Treatment Group ◽

Tau Protein ◽

Protein Level ◽

Control Group ◽

Sprague Dawley ◽

Treatment Groups ◽

Turmeric Extract ◽

Sham Control Group

BACKGROUND: Repetitive traumatic brain injury (RTBI) has gained much attention in this decade, especially in contact sports athletes and military personals. This injury is correlated with early neurodegenerative changes that are marked with the increased of tau protein. Turmeric extract (TE) is a well-known anti-inflammation and antioxidant that decreases tau protein expression in neurodegenerative disease. AIM: This study aimed to prove the effect of TE on tau protein level after RTBI. METHODS: Forty Sprague Dawley mice were divided into four groups, i.e. negative sham control group, the control group, and two treatment groups. A weight drop model was used by applying a 40-gram mass that was dropped from a 1-meter height onto the vertex of the head, with a total frequency of 12 times, divided into 4 days (day 0, 1, 3, and 7; 3 traumas on each day). TE was given to all treatment groups with 500 mg/kg BW doses once daily. The first treatment group had TE for seven days along the trauma. The second treatment group had pretreatment TE extract, given from seven days before first trauma and continued along the trauma protocol days. Tau protein level was measured on brain and serum using ELISA method. RESULTS: There was a significant reduction of tau protein level in both treatment groups compared to trauma group, either in serum or brain, but we also found significant differences regarding brain tau level between the treatment and pretreatment group. CONCLUSION: This study might provide evidence of with the role of pretreatment TE in RTBI.

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Androgenic Effects of Cinnamomum camphora in Male Sprague-dawley Rats

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2019/v31i730310 ◽

2019 ◽

pp. 1-13

Author(s):

O. H. Ayoade ◽

G. G. Akunna ◽

F. I. Duru

Keyword(s):

Dose Group ◽

Low Dose ◽

Activity Level ◽

Control Group ◽

High Dose ◽

Activity Levels ◽

Sprague Dawley ◽

Treatment Groups ◽

Sprague Dawley Rats ◽

Medium Dose

This study evaluated camphora-induced androgenic and histopathological changes in male Sprague-Dawley rats. Thirty-five animals weighing 200 g±20 g were used for this study and randomly divided equally into five groups, with seven rats in each group. Group A animals (normal control group) were served water and rat chow only; Groups B-D (treatment groups) were orally administered camphora in doses of 1 g/kg (Low-dose), 2 g/kg (Medium-dose) and 4 g/kg (High-dose) respectively while Group E (vehicle group) were orally administered 6 mL/kg olive oil (a solvent for camphora) per day for 56 days. There was a significant decrease (P< .05) in activity levels of Follicle-Stimulating Hormone (FSH); Superoxide Dismutase (SOD) when the treatment was compared with the control group. Also, a significant decrease (P< .05) in activity level of FSH was observed when the Medium-dose group was compared with Low-dose group. Insignificant irregular pattern in activity level of Testosterone was observed across the treatment groups when compared with the control. However, a significant increase (P< .05) in activity level of Testosterone was observed when the High-dose group was compared with the Medium-dose group. There was a significant increase (P< .05) in activity levels of Luteinizing Hormone (LH) and Malondialdehyde (MDA) when the treatment was compared with the control group. Semen analysis showed reduction in sperm concentration, motility and morphology with increasing concentration of camphora. Significant decrease was recorded in testicular weight when High-dose group was compared to Control and Low-dose groups. Histopathological changes were seen in the testes of the camphor administered groups, ranging from mild disintegrated interstitial tissues in Low-dose to severe degeneration and disintegration of both seminiferous and interstitial tissues in the testes in the Medium-dose and High-dose groups. In conclusion, camphora had androgenic and toxic effects on testis and may cause testicular tissue damage.

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Cytoglobin expression in oxidative stressed liver during systemic chronic normobaric hypoxia and relation with HIF-1α

Medical Journal of Indonesia ◽

10.13181/mji.v23i3.1025 ◽

2014 ◽

Vol 23 (3) ◽

pp. 133-8 ◽

Cited By ~ 1

Author(s):

Sri W.A. Jusman ◽

Febriana C. Iswanti ◽

Franciscus D. Suyatna ◽

Frans Ferdinal ◽

Septelia I. Wanandi ◽

...

Keyword(s):

Oxidative Stress ◽

Normobaric Hypoxia ◽

Control Group ◽

Strongly Correlated ◽

Sprague Dawley ◽

Oxidative Stress Parameter ◽

Treatment Groups ◽

Stress Parameter ◽

Sprague Dawley Rats ◽

Mrna And Protein Expression

Background: Liver is sensitive against hypoxia and hypoxia will stabilize HIF-1α. At the same time, hypoxia will produce reactive oxygen species (ROS) which can be scavenged by Cygb. The purpose of our study is to know, if normobaric hypoxia can induce Cygb expression and its association with HIF-1α stabilization.Methods: This is an experimental study using 28 male Sprague-Dawley rats, 150-200 g weight. Rats are divided into 7 groups: control group and treatment groups that are kept in hypoxic chamber (10% O2: 90% N2) for 6 hours, 1, 2, 3, 7 and 14 days. All rats are euthanized after treatment and liver tissue are isolated, homogenized and analyzed for oxidative stress parameter, expression of Cygb and HIF-1α.Results: Expression of Cygb mRNA and protein was increased on the day-1 after treatment and reach the maximum expression on the day-2 of hypoxia treatment. But, the expression was decreased after the day-3 and slightly increased at the day-14 of hypoxia. The correlation between expression of Cygb and oxidative stress parameter was strongly correlated. Cygb mRNA, as well as protein, showed the same kinetic as the HIF-1, all increased about day-1 and day-2.Conclusion: Systemic chronic hypoxia and/or oxidative stress up-regulated HIF-1α mRNA which is correlated with the Cygb mRNA and protein expression. Cygb mRNA as well as Cygb protein showed the same kinetic as the HIF-1, all increased about day-1 and day-2 suggesting that Cygb could be under the regulation of HIF-1, but could be controlled also by other factor than HIF-1.

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Black Cumin Seed Oil Antidiabetogenic by Increasing Pancreatic P53 Expression

International Journal of Public Health Science (IJPHS) ◽

10.11591/ijphs.v7i3.13694 ◽

2018 ◽

Vol 7 (3) ◽

pp. 207

Author(s):

Akrom Akrom ◽

Rizma Nurfadjrin ◽

Endang Darmawan ◽

Titiek Hidayati

Keyword(s):

Seed Oil ◽

Positive Control ◽

Control Group ◽

Sprague Dawley ◽

P53 Expression ◽

Black Cumin ◽

Treatment Groups ◽

Glucose Levels ◽

Black Cumin Seed ◽

Cumin Seed

Black cumin seed oil (BCSO) contains many thymoquinone and unsaturated fatty acids that act as antioxidants. Thymoquinone was thought to inhibit pancreatic damage and prevent hyperglycemia by involving p53. The study aimed to determine the BCSO effect on Malondialdehyde (MDA) levels and p53 expression of pancreatic tissues in alloxan-induced Sprague Dawley (SD) rats. This study used Pre and Post Test with Control Group Design with 49 male Sprague Dawley rats aged 30 days weighing 150 - 300 gram. Rats were divided into 7 groups: Group I, the normal control group receiving standard feeding and drinking; Group II, the negative control group receiving alloxan; Group III & IV, the treatment groups, receiving BCSO with a dose of 6.9 mg/KgBW (BCSO6.8) and 68 mg/KgBW (BCSO68 group); Group V, the positive control 1 group receiving simvastatin 10 mg/KgBW; Group VI, the positive control 2 group receiving vitamin C 18 mg/200mgBW; Group VII, the solvent control receiving DMSO. The treatment groups received two different doses per day for 9 days orally. Blood MDA and glucose levels were determined by spectrophotometry and p53 expression of pancreas tissues were read by a pathologist. The results show that the BCSO68 group had a decreased activity of MDA and glucose but a higher expression of p53 in pancreatic tissues compared to the BCSO6.8 group. Decreased Malondialdehyde levels in the BCSO68 group were similar to those in the vitamin C group but lower than those in the simvastatin group (p<0.05). It can be concluded that the BCSO administration of 68 mg/KgBW per day can decrease blood Malondialdehyde and glucose levels and increase p53 expression.

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