title: Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism.
abstract: The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn) treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group) and the B401 (50 mg/kg) group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg) was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO) production, levels of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), expression levels of factors governing angiogenesis (vascular endothelial growth factor), oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal), inflammation (tumor necrosis factor alpha), apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose) polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3) were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in penile corpus cavernosum. We suggest that the herbal formula B401 may serve as a potential dietotherapeutic supplement for penile toxicity or dysfunction in aging males.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Sheue-Er
authors.initials: SE
authors.lastname: Wang
authors.affiliation: Brion Research Institute of Taiwan, Taipei, Taiwan.
authors.forename: Shuenn-Jyi
authors.initials: SJ
authors.lastname: Sheu
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015386:Hazardous Substances / Q000633:toxicity*; D000075322:Heavy Metal Poisoning; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D010413:Penis / Q000187:drug effects*; D028321:Plant Preparations / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011041:Poisoning / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000975:Antioxidants; C000604562:B401 herbal formula; D004365:Drugs, Chinese Herbal; D015386:Hazardous Substances; D018836:Inflammation Mediators; D028321:Plant Preparations; D042461:Vascular Endothelial Growth Factor A; D008345:Manganese
keywords: apoptosis; herbal formula; inflammation; manganism; oxidative stress