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1.
Brain undergoes neurodegeneration when excess free radicals overwhelm antioxidative defense systems during senescence, head trauma and/or neurotoxic insults. A site-specific accumulation of ferrous citrate-iron complexes in the substantia nigra dopaminergic neurons could lead to exaggerated dopamine turnover, dopamine auto-oxidation, free radical generation, and oxidant stress. Eventually, this iron-catalyzed dopamine auto-oxidation results in the accumulation of neuromelanin, a progressive loss of nigral neurons, and the development of Parkinson's disease when brain dopamine depletion is greater than 80%. Emerging evidence indicates that free radicals such as hydroxyl radicals ((.-)OH) and nitric oxide ((.-)NO) may play opposite role in cell and animal models of parkinsonism. (.-)OH is a cytotoxic oxidant whereas oNO is an atypical neuroprotective antioxidant. (.-)NO and S-nitrosoglutathione (GSNO) protect nigral neurons against oxidative stress caused by 1-methyl-4-phenylpyridinium (MPP(+)), dopamine, ferrous citrate, hemoglobin, sodium nitroprusside and peroxynitrite. MPP(+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), increases the nigral uptake of iron complexes and dopamine overflow leading to the generation of (.-)OH, protein oxidation, lipid peroxidation, and associated retrograde degeneration. In addition to GSNO, MPP(+)-induced oxidative neurotoxicity can be prevented by antioxidants including selegiline, 7-nitroindazole, 17beta-estradiol, melatonin, alpha-phenyl-tert-butylnitrone and U78517F. Similar to selegiline, 7-nitroindazole is a MAO-B inhibitor, which blocks the bio-activation of MPTP and oxidative stress. Freshly prepared but not light exposed, (.-)NO-exhausted GSNO is about 100 times more potent than the classic antioxidant glutathione. Via S-nitrosylation, GSNO also inhibits proteolysis and cytotoxicity caused by caspases and HIV-1 protease. Furthermore, in addition to protection against serum deprivation stress, the induction of neuronal NOS1 in human cells increases tolerance to MPP(+)-induced neuro-toxicity since newly synthesized (.-)NO prevents apoptosis possibly through up-regulation of bcl-2 and down regulation of p66(shc). In conclusion, reactive oxygen species are unavoidable by-products of iron-catalyzed dopamine auto-oxidation, which can initiate lipid peroxidation, protein oxidation, DNA damage, and nigral loss, all of which can be prevented by endogenous and exogenous (.-)NO. Natural and man-made antioxidants can be employed as part of preventative or neuroprotective treatments in Parkinson's disease and perhaps dementia complexes as well. For achieving neuroprotection and neuro-rescue in early clinical parkinsonian stages, a cocktail therapy of multiple neuroprotective agents may be more effective than the current treatment with extremely high doses of a single antioxidative agent. 相似文献
2.
Toume Kazufumi Hou Zhiyan Yu Huanhuan Kato Mitsuru Maesaka Miki Bai Yanjing Hanazawa Shiho Ge Yuewei Andoh Tsugunobu Komatsu Katsuko 《Journal of natural medicines》2020,74(3):615-615
Journal of Natural Medicines - The article Search of anti-allodynic compounds from Plantaginis Semen, a crude drug ingredient of Kampo formula “Goshajinkigan”. 相似文献
3.
Background
Atopic dermatitis is a chronic and severe pruritic skin disease. Interlukin-31 (IL-31) has been recently demonstrated to be one of the key pruritogens in atopic dermatitis. However, the mechanisms underlying IL-31-induced itching remains unclear. In our previous study, we have shown that thromboxane (TX) A2 is involved in itch-associated responses in mice with atopy-like skin diseases.Methods
IL-31 was given intradermally into the rostral back of ICR mice and the hind-paw scratching to the injection site were counted. Expression of TX synthase and IL-31 receptors were analyzed using immunohistochemical staining or RT-PCR in mouse skin or primary cultures of mouse keratinocytes. The concentration of TXB2, a metabolite of TXA2, in the skin and the culture medium of primary cultures of mouse keratinocytes was measured using enzyme immunoassay. The concentration of intracellular Ca2+ ions in mouse keratinocytes was measured using the calcium imaging method.Results
An intradermal injection of IL-31 elicited scratching, an itch-related response, in mice. The scratching was inhibited by TP TXA2 receptor antagonist DCHCH. The distribution of TX synthase and IL-31RA receptor was mainly epidermal keratinocytes in the skin. The primary cultures of keratinocytes expressed the mRNAs of TX synthase and IL-31 receptors. IL-31 increased the concentration of TXB2, which was inhibited by TX synthase inhibitor sodium ozagrel and EGTA, in the skin and the culture medium of primary cultures of keratinocytes. IL-31 increased the concentration of intracellular Ca2+ ions in mouse keratinocytes.Conclusion
It is suggested that IL-31 elicits itch-associated responses through TXA2 produced from keratinocytes. 相似文献4.
Yoshihiro Inami Tsugunobu Andoh Yasushi Kuraishi 《Journal of pharmacological sciences》2013,121(3):242-245
Effects of chlorogenic acid on surfactant-induced itching were studied in mice. Topical application of sodium laurate increased hind-paw scratching, an itch-related response, 2 h after application, which was inhibited by topical post-treatment with chlorogenic acid. Sodium laurate increased the histamine content and 53-kDa l-histidine decarboxylase in the epidermis, which were also inhibited by post-treatment with chlorogenic acid. These results suggest that topical chlorogenic acid is effective in the prevention of itching induced by anionic surfactants. The inhibitory activity of chlorogenic acid may be due to the inhibition of an increase in histamine in the epidermis. 相似文献
5.
Zhang HW Iida Y Andoh T Nojima H Murata J Saiki I Kuraishi Y 《Journal of pharmacological sciences》2003,91(2):167-170
Melanoma inoculation induced marked mechanical allodynia and hyperalgesia in the periphery of the melanoma mass in mice from about day 10 post-inoculation. In the middle of the tumor, there were slight hyperalgesia and response disappearance in the early and late phases, respectively. PGP9.5-like immunoreactivities increased in the epidermis of the periphery of the tumor and disappeared from the dermis of the middle on day 18 post-inoculation, without apparent alterations on day 10. When using this pain model, one should consider the tumor site-dependent responses. 相似文献
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Punam Gauchan Tsugunobu Andoh Atsushi Kato Atsushi Sasaki Yasushi Kuraishi 《Journal of pharmacological sciences》2009,109(3):469-472
This study examined in mice whether limaprost, a prostaglandin E1 analog, would relieve allodynia induced by chemotherapeutic agents. Single intraperitoneal injections of paclitaxel, oxaliplatin, and vincristine sulfate induced and gradually increased mechanical allodynia. Repeated administration of limaprost alfadex inhibited the late, but not early, phase of mechanical allodynia induced by paclitaxel and oxaliplatin, but not vincristine. Paclitaxel and oxaliplatin, but not vincristine, gradually decreased peripheral blood flow, which was prevented by limaprost. These results suggest that limaprost is effective against mechanical allodynia induced by paclitaxel and oxaliplatin, which may be due to inhibition of the decrease in peripheral blood flow. 相似文献
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9.
Anti-pruritic effects of the antihistamine bepotastine besilate were studied in mice. Bepotastine besilate (10 mg/kg) inhibited scratching induced by an intradermal injection of histamine (100 nmol/site), but not serotonin (100 nmol/site). Bepotastine besilate (1-10 mg/kg, oral) dose-dependently suppressed scratching induced by substance P (100 nmol/site) and leukotriene B(4) (0.03 nmol/site). An intradermal injection of substance P (100 nmol/site) increased the cutaneous concentration of leukotriene B(4), which was not affected by bepotastine besilate (10 mg/kg, oral). Leukotriene B(4) increased Ca(2+) concentration in cultured neutrophils, which was suppressed by bepotastine besilate (1-100 microM). Leukotriene B(4) increased Ca(2+) concentration in cultured dorsal root ganglion neurons, which was also suppressed by bepotastine besilate (100 microM). The results suggest that the inhibition of the actions of leukotriene B(4) as well as histamine is involved in the anti-pruritic effect of bepotastine besilate. 相似文献
10.
Takasaki I Taniguchi K Komatsu F Sasaki A Andoh T Nojima H Shiraki K Hsu DK Liu FT Kato I Hiraga K Kuraishi Y 《Pain》2012,153(3):585-592
To identify endogenous factors involved in herpetic pain, we performed genome-wide microarray analysis of the spinal cord of mice that suffered from herpetic allodynia induced by inoculation with herpes simplex virus type 1, which revealed marked induction of galectin-3, a β-galactoside-binding lectin. Therefore, we investigated the role of galectin-3 in herpetic allodynia. The expression levels of galectin-3 mRNA and protein were increased with a temporal pattern similar to that of herpetic allodynia. Galectin-3-expressing cells were mainly localized in the superficial dorsal horn, round in shape, and positive for the macrophage/microglia markers Iba-1 and F4/80. In the deep dorsal horn, there were Iba-1-positive cells with ramified and stout processes, which were negative for galectin-3. In the superficial dorsal horn, there were many CD3-positive T cells, but most of the galectin-3-expressing cells were negative for CD3. Galectin-3-expressing cells were negative for the neuronal marker NeuN and the astrocyte marker glial fibrillary acidic protein antibody. Deficiency in galectin-3 markedly reduced herpetic allodynia, without showing an effect on herpes zoster-like skin lesions. Intrathecal injection of galectin-3 produced mechanical allodynia in naive mice, and intrathecal injections of anti-galectin-3 antibodies significantly reduced herpetic allodynia. The present results suggest that galectin-3 in infiltrating macrophages and/or resident microglia in the spinal dorsal horn contributes to herpetic allodynia. Galectin-3 may be a new therapeutic target for the treatment of herpes zoster-associated pain. 相似文献