scholarly journals Effects of Repeated Treatment with Monoamine-Transporter-Inhibitor Antidepressants on Pain-Related Depression of Intracranial Self-Stimulation in Rats

2019 ◽  
Author(s):  
LP Legakis ◽  
L Karim-Nejad ◽  
SS Negus
Keyword(s):  
Weight Loss ◽  
Positive Control ◽  
Negative Control ◽  
Selective Inhibitor ◽  
Kappa Opioid Receptor ◽  
Repeated Treatment ◽  
Sprague Dawley ◽  
Monoamine Transporter ◽  
Analgesic Effects ◽  
Self Stimulation

ABSTRACTSynaptic neurotransmission with dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is terminated primarily by reuptake into the presynaptic terminal via the DA, NE, and 5-HT transporters (DAT/NET/SERT, respectively). Monoamine transporter inhibitors constitute one class of drugs used to treat pain, and emergence of analgesic effects by these compounds often requires repeated treatment for days or weeks. The present study compared antinociceptive effects produced by repeated treatment with monoamine transporter inhibitors in a preclinical assay of pain-related depression of positively reinforced operant responding. Adult male Sprague-Dawley rats equipped with microelectrodes targeting a brain-reward area responded for pulses of electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. Intraperitoneal injection of dilute lactic acid served as a noxious stimulus that repeatedly depressed ICSS and also produced weight loss during 7 days of repeated acid administration. Both acid-induced ICSS depression and weight loss were blocked by repeated pretreatment with the nonsteroidal anti-inflammatory drug ketorolac (a positive control) but not by the kappa opioid receptor agonist U69,593 (a negative control). Like ketorolac, the DAT/NET inhibitor bupropion fully blocked acid-induced ICSS depression and weight loss throughout all 7 days of treatment. Conversely, the NET-selective inhibitor nortriptyline and SERT-selective inhibitor citalopram produced antinociception only after several days of repeated treatment, and weight loss was attenuated by citalopram but not by nortriptyline. These results support effectiveness of bupropion to alleviate signs of pain-related behavioral depression in rats and further suggest that nortriptyline and citalopram produce a more gradual onset of antinociception during repeated treatment.

scholarly journals The Analgesic Effect of Aconitum Sinomontanum Nakai Pharmacopuncture in Sprague-Dawley Rats

2021 ◽  
Vol 38 (2) ◽  
pp. 140-145
Author(s):  
Jung Hee Lee ◽  
Yun Kyu Lee ◽  
Hyun-Jong Lee ◽  
Jae Soo Kim
Keyword(s):  
Analgesic Effect ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Lidocaine Group ◽  
Analgesic Effects ◽  
Sd Rats

Background: Aconitum sinomontanum Nakai (ASN) has been reported to have analgesic effects. In this study an animal model of pharmacopuncture using ASN (100-500 mg/kg) was examined.Methods: Sprague-Dawley (SD) rats (n = 40) were randomly assigned to ASN-Low (1 mg/mL, 1.8 mL, ASN-L), ASN-Intermediate (5 mg/mL, 1.8 mL, ASN-M), ASN-High (10 mg/mL, 1.8 mL, ASN-H), negative control (0.2 mL normal saline), and positive control (0.2 mL 0.5% lidocaine) groups. All experiments were administered to the rats’ left hind leg. The analgesic response was assessed by monitoring the physical (hot plate, and von Frey test) and chemical (formalin) responses to pain.Results: All ASN pharmacopuncture groups demonstrated significant differences in pain response to the hot plate test, von Frey test, and formalin test, compared to the control group (p < 0.05). The response of the ASN-M group and ASN-H groups to the hot plate, the formalin, and the von Frey tests were significantly different, compared to the lidocaine group (p < 0.05).Conclusion: ASN pharmacopuncture had a significant analgesic effect on SD rats in response to physical and chemical models of pain.

Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats

2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek
Keyword(s):  
Alcohol Dehydrogenase ◽  
High Performance ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Methanol Poisoning ◽  
Sprague Dawley Rats

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.

UJI EFEK ANALGESIK EKSTRAK ETANOL DAUN KERSEN (Muntingia calabura L.) PADA MENCIT PUTIH JANTAN (Mus musculus) DENGAN INDUKSI NYERI ASAM ASETAT

2017 ◽  
Vol 2 (2) ◽  
pp. 147
Author(s):  
Triswanto Sentat ◽  
Susiyanto Pangestu
Keyword(s):  
Analgesic Effect ◽  
Ethanol Extract ◽  
Positive Control ◽  
Negative Control ◽  
Control Treatment ◽  
Treatment Groups ◽  
Analgesic Effects ◽  
Significant Difference ◽  
Analgesic Dose ◽  
Muntingia Calabura

Kersen leaf (Muntingia calabura L.) contains tannins, flavonoids and polyphenol compounds allegedly have analgesic effect. The objective was to determine the analgesic effect of ethanol extract of kersen leaves and to determine the most effective analgesic dose. This study was an experimental research. Leaves were extracted with ethanol 70% and the analgesic effect test was divided into 5 groups: negative control treatment (distilled water), positive control (mefenamic acid 2.6mg/kg), kersen leaf ethanol extract first dose (100mg/kg), second dose (200mg/kg) and tthird dose (400mg/kg). Giving treatments by oral, after 30 minutes, the mices were given a pain inductor with 0.5% acetic acid by intra peritonial administration. Analgesic power was calculated by counting the number of writhing in mice for 1 hour. The results showed that the ethanol extract of cherry leaf has analgesic effect. From the calculation of the first dose analgesic power (42.9%), second dose (59.4%) and the third dose 69.9%. Statistical test results kruskal wallis value of p=0.011 (p<0.05) showed a significant difference between all analgesic treatment groups. The conclusion of this study is all of the ethanol extract had analgesic effects on male white mice, whereas a dose of 400mg/kg is the most effective analgesic dose.

scholarly journals Multi Floral Honey Has a Protective Effect against Mammary Cancer Induced by 7,12-Dimethylbenz(a)anthracene in Sprague Dawley Rats

2017 ◽  
Vol 9 (2) ◽  
pp. 196 ◽  
Author(s):  
Hamed R. Takruri ◽  
Maha S. Shomaf ◽  
Saida F. Shnaigat
Keyword(s):  
Protective Effect ◽  
Mammary Cancer ◽  
Histopathological Examination ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Light Cycle ◽  
Sprague Dawley ◽  
Dark Light

This research was conducted to study the protective effect of bee honey on the 7,12-dimethylbenz(a)anthracene (DMBA)- induced breast cancer in rat model. The study consisted of three groups: honey group, positive control group (PC), and negative control group (NC) to which the carcinogen was not administered. All rats were fed the diet recommended by the American Institute of Nutrition for growing rats (AIN-93G), with addition of honey (50 g/kg diet) to the honey group. All Rats were fed their diets ad libitum on 12 hours dark/light cycle. At the age of 50 days all rats in the honey and PC groups were gavaged once by the carcinogen DMBA with a dose of 80 mg/kg body Wt. After three weeks of carcinogen administration, rats were palpated weekly to detect any tumor growth. After 18 weeks, all rats were sacrificed. The palpable structures and the mammary glands along with associated lymph nodes were removed and fixed in saline formalin and prepared for histopathological examination. The results revealed that the honey group diet significantly (p < 0.05) reduced the incidence rate of mammary cancer, palpable tumor multiplicity, tumor size and weight compared to the PC group. In conclusion, multi floral honey has a protective effect against DMBA- induced mammary cancer in the initiation, promotion, and progression stages of DMBA-induced mammary carcinogenesis. However, further research is needed to reveal the mechanisms that might have contributed to the preventive effect of honey against mammary cancer.

scholarly journals Application of Scaevola taccada (Gaertn.) Roxb. Reduce Pro-inflammatory Cytokines Interleukin-1β in Sprague Dawley Mice Suffering from Mastitis

2020 ◽  
Vol 8 (A) ◽  
pp. 423-427
Author(s):  
Prihantono Prihantono ◽  
Salman Ardi Syamsu ◽  
Nilam Smaradhania ◽  
Mardiana Ahmad ◽  
Nurul Aini Siagian ◽  
...  
Keyword(s):  
Body Weight ◽  
Positive Control ◽  
Mean Value ◽  
Negative Control ◽  
Interleukin 1Β ◽  
Sprague Dawley ◽  
Leaf Extracts ◽  
Group Iii ◽  
Group I ◽  
The Mean

BACKGROUND: Mastitis is an inflammation of the breast tissue, usually caused by bacteria. Mastitis stimulates pro-inflammatory cytokines. The cytokine interleukin-1β (IL-1β) is a crucial mediator of the inflammatory response. This cytokine has adverse effects of hosting immunity that mediates resistance to pathogens and also exacerbates damage during chronic disease and acute tissue injury. Scaevola taccada (Gaertn.) Roxb. has been used as an ethnomedicine for healing sores in several provinces in Indonesia. AIM: This study aimed to assess the profile of pro-inflammatory cytokine IL-1β through the treatment effect of leaf extracts of S. taccada (Gaertn.) Roxb. as adjuvant for healing mastitis. METHODS: This study was a true control group experiment using the pre-test-post-test control design aimed to measure the effect of hydroalcoholic compounds in leaf extracts of S. taccada on the systemic pro-inflammatory activity of interleukin-1β (IL-1β). The treated animals were 18 mice of Sprague Dawley strain induced by Staphylococcus aureus. These treated mice were divided into three groups in which each group consisted of six mice. The mice in the Group I (negative control) were given 1 ml aquabides/250 g body weight, those in the Group II (positive control) were delivered with 9.6 mg/ml amoxicillin/250 g body weight, and those in the Group III (experimental) were given 9.6 mg amoxicillin/250 g body weight + 400 mg/ml leaf extracts of S. taccada/g body weight for 5 days, respectively. Pathological examinations were carried out from the inflamed tissues to prove the healing process of the treated mice. IL-1Β levels were determined using the enzyme-linked immunosorbent assay method. Data were analyzed using ANOVA and post hoc tests. RESULTS: There were statistically significant differences of IL-1β levels after the administration of leaf extracts of S. taccada among all the treated mice groups at p < 0.05. The Group III had the lowest IL-1β level with the mean value ± 1.45 pg/ml compared to the IL-1β level in the Group II (positive control) with the mean value ± 3.82 pg/ml and the IL-1β level in the Group I (negative control) with the with mean value ± 5.22 pg/ml. The pathological analysis of breast tissues of the treated mice proved that leaf extracts of S. taccada (Gaertn Roxb.) could reduce damaged tissues, cellular infiltration, and subcutaneous edema induced by this pathogenic microorganism. CONCLUSION: Leaf extracts of S. taccada had a significant function as adjuvant for healing mastitis by reducing pro-inflammatory cytokine IL-1β.

scholarly journals PENGARUH SINBIOTIK KEFIR PISANG BATU TERHADAP KADAR KOLESTEROL-LDL DAN KOLESTEROL-HDL TIKUS MODEL SINDROM METABOLIK

2020 ◽  
Vol 7 (2) ◽  
pp. 280-288
Author(s):  
Dina Khoiriyah ◽  
Taufik Maryusman ◽  
Santi Herlina
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Positive Control ◽  
Negative Control ◽  
Sprague Dawley ◽  
Musa Balbisiana ◽  
Cholesterol Levels ◽  
Sprague Dawley Rats

Effect of Banana Kefir Synbiotic on LDL-Cholesterol and HDL-Cholesterol of Metabolic Syndrome Rats Metabolic syndrome (SM) is characterized by several risk factors including dyslipidemia. This study aims to analyze the effect of kefir synbiotic produced from banana stone flour (Musa balbisiana) on LDL-cholesterol and HDL-cholesterol of metabolic syndrome rat model. The 24 Sprague Dawley rats were divided into four groups, namely negative control (healthy rats fed standard feed), positive control (metabolic syndrome rats fed standard feed), treatment I and treatment II (metabolic syndrome rats each given synbiotic kefir banana stone flour 1.8 mL/200 g mouse BW/day and 3.6 mL/200 g mouse BW/day, respectively). The intervention was carried out for three weeks. After the intervention, the levels of LDL-cholesterol in treatment I and II experienced a decrease of 44.66% and 56.94%, respectively, while the-HDL-cholesterol levels in treatment I and II experienced an increase of 104.5% and 172.71%, respectively. The biggest change occurred in treatment II. Synbiotic kefir banana stone flour improved lipid profile in metabolic syndrome rats. Sindrom metabolik (SM) ditandai dengan beberapa faktor risiko termasuk dislipidemia. Penelitian ini bertujuan untuk menganalisis pengaruh sinbiotik kefir tepung pisang batu (Musa balbisiana) terhadap kadar kolesterol-LDL dan kolesterol-HDL tikus model SM. Subjek menggunakan 24 ekor tikus Sprague Dawley yang dibagi menjadi empat kelompok, yaitu kontrol negatif (tikus sehat yang diberi pakan standar), kontrol positif (tikus model SM yang diberi pakan standar), perlakuan I dan perlakuan II (tikus model SM yang masing-masing diberi sinbiotik kefir tepung pisang batu 1,8 mL/200 g BB tikus/hari dan 3,6 mL/200 g BB tikus/hari). Proses intervensi dilakukan selama tiga minggu. Setelah intervensi, kadar kolesterol-LDL perlakuan I dan II mengalami penurunan sebesar 44,66% dan 56,94%, sedangkan kadar kolesterol-HDL perlakuan I dan II mengalami peningkatan sebesar 104,5% dan 172,71%. Perubahan terbesar terjadi pada perlakuan II. Sinbiotik kefir tepung pisang batu memperbaiki profil lipid tikus sindrom metabolik.

Buprenorphine alleviation of pain does not compromise the rat monoarthritic pain model

2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson
Keyword(s):  
Rat Model ◽  
Joint Stiffness ◽  
Positive Control ◽  
Negative Control ◽  
Pain Tolerance ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
A Minor

Abstract Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.

scholarly journals Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Elnaz Saki ◽  
Latifah Saiful Yazan ◽  
Razana Mohd Ali ◽  
Zalinah Ahmad
Keyword(s):  
Crude Extract ◽  
Positive Control ◽  
Negative Control ◽  
Vital Role ◽  
Aberrant Crypt Foci ◽  
Chemical Compositions ◽  
Not Given ◽  
Sprague Dawley ◽  
Therapeutic Modalities ◽  
Rough Rice

Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR) crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age) were randomly divided into 5 groups which were (G1) induced with azoxymethane (AOM) and not given GRR (positive control), (G2) induced with AOM and given 2000 mg/kg GRR, (G3) induced with AOM and given 1000 mg/kg GRR, (G4) induced with AOM and given 500 mg/kg GRR, and (G5) not induced with AOM and not given GRR crude extract (negative control). To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg) for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF) were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.

scholarly journals The Effect of Tempeh Gembus Variations to Serum Levels of High Sensitivity C-Reactive Protein (hsCRP) and Serum Levels of Fibrinogen of Sprague Dawley Rats with Aterogenic Diet

2018 ◽  
Vol 25 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Partika Kharunia Dewi ◽  
Diana Nur Afifah ◽  
Ninik Rustanti ◽  
Mohammad Sulchan ◽  
Gemala Anjani
Keyword(s):  
Serum Levels ◽  
Negative Control Group ◽  
Positive Control ◽  
Atherogenic Diet ◽  
Negative Control ◽  
Positive Control Group ◽  
Control Group ◽  
Standard Diet ◽  
Sprague Dawley ◽  
Significant Difference

Abstract Background and aims: Cardiovascular diseases are widespread and causes many deaths in the world. The concentration of acute phase protein: C-reactive protein (CRP) and fibrinogen will rise dramatically when inflammation happens, which that can be used as an early marker of cardiovascular disease risk. Tempeh gembus contains fiber, unsaturated fatty acids and isoflavones are believed to reduce the inflammatory reaction. The aim of the study was to determinate the effect of tempeh gembus variations to levels of hcCRP and levels of fibrinogen of Sprague Dawley rats with atherogenic diet. Material and methods: This study was quasi-experimental with posttest only randomized control group design using 35 Sprague Dawley mice. The rats were randomized into 5 groups: negative control group given the standard diet, the positive control group given standard diet and atherogenic diet, and three treatment groups were given the standard diet, atherogenic diet and variation of tempeh gembus (tempeh gembus, heated tempeh gembus and tempeh gembus with bromelain enzyme) for 28 days. Serum levels of hsCRP and fibrinogen examined using ELISA (Enzyme-linked Immunosorbent Assay). Results and conclusions: The administration of tempeh gembus with bromelain enzyme is the most effective treatment for hsCRP serum level indicated a significant difference (p=0.028) between the negative control group, positive control group and first group with the third group. Fibrinogen serum levels showed significant differences in all treatment groups (p =0.042), administration of tempeh gembus with bromelain enzyme is the most effective treatment is shown by a significant difference between the negative control group and the positive control group with third group. The administration of tempeh gembus with bromelain enzyme for 28 days can reduce the serum levels of hsCRP and fibrinogen on rats significantly.

scholarly journals Hepatoprotective Activity of Ethanol Extract of Figs Leaves (Ficus carica L.) with SGOT & SGPT Parameters in Sprague Dawley Female Rats Induced by Paracetamol

2021 ◽  
Vol 7 (2) ◽  
pp. 110-119
Author(s):  
Muhammad Fariez Kurniawan ◽  
Herdita Nugraheny Kusuma Wardany
Keyword(s):  
Ethanol Extract ◽  
Test Dose ◽  
Hepatoprotective Activity ◽  
Positive Control ◽  
Negative Control ◽  
Ficus Carica ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Serum Glutamic Oxaloacetic Transaminase

Background: Long-term usage of paracetamol damages liver cells characterized by the increasing levels of Serum Glutamic Pyruvic Transaminase (SGPT) and Serum Glutamic Oxaloacetic Transaminase (SGOT). Figs (Ficus carica L.) leaves contain high flavonoid compounds that able to act as hepatoprotector agents which inhibited the process of liver damage. Objectives: This study aims to determine the dose characteristics and hepatoprotective activity of figs (Ficus carica L.) leaves extract. Material and Methods: The hepatoprotective activity of figs extract (Ficus carica L.) was determined by measuring SGPT & SGOT levels in rat blood. 42 rats were prepared, divided into 7 groups: normal control group, negative control given paracetamol with a dose 40 mg/200 g BW, positive control given hepamax®, base control given Na CMC, and 3 test dose groups given figs leaves extract with a dose of 40 mg/200 g BW, 80 mg BW/200 g BW and 160 mg/200 g BW. The treatment was carried out for 14 consecutive days. Paracetamol was given for 14 days, while positive control, 3 test dose groups and base control were given on day 7 to day 14.  Rats blood samples were taken through the orbital sinuses on day 1, day 5, day 10 and day 14 after treatment began. SGPT & SGOT levels were determined using spectrophotometry with analytical methods using specific SGPT & SGOT reagent kits.  Results: The results showed that the leaves extract of figs (Ficus carica L.) proved to be able to reduce the levels of SGPT & SGOT with the most potent dosage was 40 mg/200 g BW. However, the reduction of SGPT & SGOT levels were not significantly different from other treatments. Conclusions: Figs (Ficus carica L.) leaves extract showed activity as a hepatoprotective agent, based on the reduction of SGPT & SGOT levels in rat after 14 days of treatment.

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