Changes of Tissue Blood Flow in Mice Loaded with SART (Repeated Cold) Stress or Restraint and Water Immersion Stress and the Effect of Administered Neurotropin

Hata, Taeko; Kita, Tomitaro; Kawabata, Atsufumi; Itoh, Eiji; Nishimura, Yoshitaka

doi:10.1254/jjp.41.69

Cited by 38 publications

(27 citation statements)

References 17 publications

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“…Neurotropin has been reported to be ef fective for moderating most of the abnormal SART stress-induced symptoms (11,12,14,17,20). Similarly, the present study showed that neurotropin blocked the increased loco motor and rearing activities and defecation caused by SART stress without influencing the behavior of non-stressed rats.…”

Section: Discussionsupporting

confidence: 79%

The Abnormal Open-Field Behavior of SART-Stressed Rats and Effects of Some Drugs on It

Hata

Nishimura

Kita

et al. 1988

Japanese Journal of Pharmacology

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Abstract-Aspart of an investigation on the behavioral characteristics of SART stressed animals, an animal model of autonomic imbalance, the open-field behavior of SARI-stressed (repeated cold-stressed) rats was studied and compared with that of rats exposed to other types of stress.In addition, the effects of several drugs on it were also studied.As compared with normal rats, SART-stressed rats exhibited increased locomotor activity, rearing and center-field penetration, together with decreased grooming and increased defecation, whereas they showed no sig nificant changes in spontaneous movements in the daytime as measured by an Animex activity meter. These behavioral abnormalities were remarkably different from those due to 1-hr cold, 48-hr cold and repeated restraint stresses. These abnormal forms of open-field behavior due to SART stress were considerably inhibited by chlorpromazine, imipramine and neurotropin at doses having no corresponding influence on normal rats; and they were partially inhibited by al prazolam, diazepam and carpipramine at doses exerting considerable influence on normal rats. The above results show that SARI-stressed rats exhibit open-field behavioral abnormalities that are different from those of rats exposed to other types of stress.Such abnormalities include excessive activity, which is considered to be caused by excessive emotionality.

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Section: Discussionsupporting

confidence: 79%

The Abnormal Open-Field Behavior of SART-Stressed Rats and Effects of Some Drugs on It

Hata

Nishimura

Kita

et al. 1988

Japanese Journal of Pharmacology

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“…Moreover, the microsampling system minimized catheter occlusion due to blood clots, blood loss and immobilization stress caused by manual blood sampling such as heart puncture, which led to minimal blood loss and stress when collecting multiple blood samples collection from a single animal. 28) In intravenous studies, there was no difference in the normalized AUCs and other pharmacokinetic parameters between 7.5 and 20 mg/kg, indicating that pharmacokinetics of sauchinone from 7.5 to 20 mg/kg were in the linear ranges in mice. In contrast to low doses (7.5 and 20 mg/kg), the normalized AUC was significantly greater and the CL (and CL NR ) was significantly slower, respectively, at 50 mg/kg.…”

Section: )mentioning

confidence: 88%

Pharmacokinetics, Tissue Distribution, and Tentative Metabolite Identification of Sauchinone in Mice by Microsampling and HPLC-MS/MS Methods

Kim

Han

Seo

et al. 2015

Biological & Pharmaceutical Bulletin

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Sauchinone, a biologically active lignan found in Saururus chinensis (Saururaceae), exerts various biological activities against jaundice, inflammatory disease, hepatic steatosis, and oxidative injury. Despite its diverse applications, there exists some information about sauchinone's pharmacokinetics but its tissue distribution, metabolism, and tentative metabolites have not been reported yet. Thus we investigated the pharmacokinetics of sauchinone in mice using microsampling and HPLC-MS/MS methods. Sauchinone presented linear pharmacokinetics at intravenous doses 7.5-20 mg/kg and oral doses 20-500 mg/kg. However, the metabolism of sauchinone was saturated and this agent presented nonlinear pharmacokinetics at 50 mg/ kg in the intravenous study. At sauchinone 20 mg/kg the F of sauchinone was 7.76% of the oral dose despite that 77.9% of sauchinone was absorbed. This might be due to extensive metabolism of sauchinone in S9 fractions of liver and small intestine. Tentative metabolites of sauchinone by oxidation, dioxidation, methylation, demethylation, dehydrogenation, or bis-glucuronide conjugation were detected in plasma and S9 fractions of liver, intestine, and kidney. The distribution of sauchinone was considerably high (tissue-to-plasma (T/P) ratios, >1) in liver, small intestine, kidney, lung, muscle, fat, or mesentery after intravenous and oral administration and in stomach and large intestine only after oral administration. The protein binding value of sauchinone was 53.0%. These pharmacokinetic data of sauchinone provide an important basis for preclinical applications and experimental methods can be adjusted to evaluate the pharmacokinetics of natural products in mice.Key words sauchinone; pharmacokinetics; metabolite identification; Saururus chinensis; mouse Pharmacokinetic studies to investigate the absorption, distribution, metabolism, and excretion (ADME) of pharmacologically active compounds of interest are essential in the preclinical and clinical process 1,2) because ADME of compounds are fundamental to therapeutic outcome in relation with the efficacy and safety.3) Along with the usages of a large number of herbal products as adjuvant or alternative medicines, the investigation of pharmacokinetic properties in herbal products has been demanding. [4][5][6][7] In addition, the tissue distribution and metabolism studies are meaningful to elucidate the pharmacological effects relying on the specific delivery and affinity of compounds to various tissues, extensive metabolizing organs, tentative metabolites identification.7-10) At these points, the inevitable and integral reasons for pharmacokinetic investigations using mice, not like rats, are as followings: it is arduous to secure a sufficient amount of herbal product using rats and the use of various knockout or xenografted mouse models to demonstrate the pharmacological activities of herbal compounds is increasing in preclinical investigations 11,12) in terms of the different physiological and pathological conditions between mice and rats. 13,14) Abo...

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“…Thus, the antinociceptive effect of neurotropin was large in diseased mice compared with its effect in normal healthy mice. This fact may be related to findings that SARI-stressed animals were in the state of reduced sympathetic tone (8,11), that some of the above-described pain on which neurotropin shows analgesic effects, are thought to have some relation to the sympathetic nervous system (17)(18)(19), and that neurotropin had regulative actions on abnormal tone in autonomic nerves (20,21).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the Analgesic Effect of Neurotropin

Hata

Kita

Itoh

et al. 1988

Japanese Journal of Pharmacology

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Abstract-Neurotropin, an extract from the inflamed skin of vaccinia virus inoculated rabbits, has been observed clinically to be effective for treating pain in patients with lumbago, SMON and other neuropathies. In the present study, we examined the mechanism of the antinociceptive effect of neurotropin in mice in relation to administration routes, opioids, and noradrenergic or GABAergic drugs , by the tail pressure method. The antinociceptive effects of neurotropin were large when administered by the i.p. and intracisternal (i.cist.) routes, but comparatively small in the case of the intrathecal (i.th.) route. Neurotropin may thus act at the supraspinal level rather than on the spinal cord. The antinociceptive effect of neurotropin was not blocked by naloxone, and no cross-tolerance developed between neurotropin and morphine. The effect of neurotropin was blocked by phentolamine and reserpine, but not by atropine. Its effect was enhanced by GABA, muscimol, aminooxyacetic acid and diaminobutyric acid, but not by baclofen , and blocked by bicuculline methiodide. From these results, the antinociceptive action of neurotropin appears to be non-opioid in nature, and may possible be mediated by the noradrenergic and GABAergic systems, but unrelated to the cholinergic system. Neurotropin, an extract from the inflamed skin of vaccinia virus-inoculated rabbits, has been clinically reported to show analgesic effects in patients with severe pain (1-5) such as that occurring in cases of lumbago, cervicodynia, SMON and various neuropa thies. Thus, neurotropin can be effectively used to treat patients with chronic pain, but not those with acute pain. In animal experi ments, neurotropin has been reported to exert strong antinociceptive effects (6) on hyperalgesia (7, 8) in SART (specific alter nation of rhythm in temperature)-stressed (repeated cold-stressed) mice (9, 10), which show symptoms of vagotonic-type dysau tonomia (11), and in other types of hyper algesic mice (12).However, the mechanism of its analgesic effect has so far not been clarified. In the present study, therefore, the antinociceptive effects of neurotropin on mice were in vestigated in relation to administration route , opioids, and noradrenergic or GABAergic agents.Neurotropin was administered to mice centrally or peripherally. Materials and MethodsMale ddY mice were used. They were housed at 22-24'C under a regime with a constant day-night rhythm and given food and water ad libitum. Normal healthy mice were used in most of the experiments, while in some experiments, SART-stressed mice were employed.For SART stress loading, the mice were kept alternately at 24 °C and 4'C at 1-hr intervals from 9 a.m. to 4 p.m. and then at 4'C from 4 p.m. to 9 a.m. the following morning. This procedure was repeated for 5 consecutive days (9, 10) and then stopped on the morning of the 6th day of stress. The stressed animals were subjected to experi ments 1 hr or more after the cessation of stress.Drugs were administered intracisternally, intrathecally or intraperitoneally.In...

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Changes of Tissue Blood Flow in Mice Loaded with SART (Repeated Cold) Stress or Restraint and Water Immersion Stress and the Effect of Administered Neurotropin

Cited by 38 publications

References 17 publications

The Abnormal Open-Field Behavior of SART-Stressed Rats and Effects of Some Drugs on It

The Abnormal Open-Field Behavior of SART-Stressed Rats and Effects of Some Drugs on It

Pharmacokinetics, Tissue Distribution, and Tentative Metabolite Identification of Sauchinone in Mice by Microsampling and HPLC-MS/MS Methods

Mechanism of the Analgesic Effect of Neurotropin

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