Carlos Castillo-Henkel

Bio: Carlos Castillo-Henkel is an academic researcher from Instituto Politécnico Nacional. The author has contributed to research in topics: Phenylephrine & Aorta. The author has an hindex of 11, co-authored 24 publications receiving 295 citations.

Kidney damage after renal ablation is worsened in endothelial nitric oxide synthase -/- mice and improved by combined administration of L-arginine and antioxidants.

Abstract: SUMMARY: Aim Reduction in nitric oxide (NO) levels during kidney failure has been related to the reaction of NO with superoxide anions to yield peroxynitrite which possesses the biological activity responsible for renal damage. However, stimulation of the NO pathway ameliorates the progression of kidney failure. Thus, it is unclear whether NO prevents or acts as the compound responsible for the cytotoxicity observed during kidney failure. Methods We evaluated the development of kidney failure in animals that were wild type and deficient in endothelial NO synthase (eNOS (−/−)) and tested the effects of an antioxidant treatment and NO precursors on the generation of superoxide anion and kidney failure parameters. Results In wild-type mice, five-sixths nephrectomy increased proteinuria from 3.0 ± 0.35 to 14.5 ± 0.76 mg protein/24 h (P < 0.05), blood pressure from 83.1 ± 1.8 to 126.6 ± 1.7 mmHg (P < 0.05), and superoxide production from 1.4 ± 0.6% to 74.3 ± 0.8% (P < 0.05). The effects of five-sixths nephrectomy on the eNOS (−/−) mice were greater compared with wild-type mice. Proteinuria increased from 6.7 ± 0.5 to 22.7 ± 2.0 mg protein/24 h (P < 0.05), blood pressure increased from 93.3 ± 0.9 to 151.2 ± 3.4 mmHg (P < 0.05), and superoxide production increased from 12.9 ± 0.5% to 99.8 ± 1.3% (P < 0.05). The nitrotyrosine levels were lower in eNOS (−/−) mice as compared to wild-type mice. A combination of L-arginine and antioxidant treatment ameliorated renal damage. The effect was improved in wild-type animals. Conclusion Our data support the relevance of NO as an antagonist to superoxide in renal tissues and suggest that the loss of this mechanism promotes the progression of kidney failure.

Bioassay-guided isolation of an anti-ulcer diterpenoid from Croton reflexifolius : role of nitric oxide, prostaglandins and sulfhydryls

Abstract: Croton reflexifolius H. B. K (Euphorbiaceae) is a very common medicinal plant in the Huastecan region of Mexico that, according to local folk medicine, is considered useful in the treatment of gastritis and gastric ulcer. We have aimed to test the validity of this practice by using the experimental model of an ethanol-induced gastric ulcer in male Wistar rats. The results showed that C. reflexifolius had gastroprotector activity, that the hexane extract had the highest protective activity (64.38+/-7.72%), and that polyalthic acid isolated from this extract was the main active gastroprotector agent. Rats treated orally with polyalthic acid showed a gastroprotective effect similar to that elicited by carbenoxolone. As with carbenoxolone, the effect elicited by polyalthic acid was attenuated by pretreatment with either N(G)-nitro-L-arginine methyl ester (70 mgkg(-1), i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mgkg(-1), s.c.), a blocker of sulfhydryl groups. This suggested that the gastroprotective mechanism of this diterpenoid involved the participation of both NO and endogenous sulfhydryl groups. Contrary to carbenoxolone, the gastroprotective effect of polyalthic acid was not affected by the inhibition of prostaglandin synthesis with indometacin (10 mgkg(-1), s. c.). In conclusion, Croton reflexifolius contains compounds with gastroprotector activity. Polyalthic acid, which was isolated from this plant, was the main compound with gastroprotector activity, having effectiveness similar to that found with the use of carbenoxolone. Whereas NO and sulfhydryl groups were involved in the mechanisms of gastroprotective action of polyalthic acid, prostaglandins were not.

Androgens and cardiovascular disease.

Abstract: Globally, cardiovascular disease will continue causing most human deaths for the foreseeable future The consistent gender gap in life span of approximately 56 yr in all advanced economies must derive from gender differences in age-specific cardiovascular death rates, which rise steeply in parallel for both genders but 5-10 yr earlier in men The lack of inflection point at modal age of menopause, contrasting with unequivocally estrogen-dependent biological markers like breast cancer or bone density, makes estrogen protection of premenopausal women an unlikely explanation Limited human data suggest that testosterone exposure does not shorten life span in either gender, and oral estrogen treatment increases risk of cardiovascular death in men as it does in women Alternatively, androgen exposure in early life (perinatal androgen imprinting) may predispose males to earlier onset of atherosclerosis Following the recent reevaluation of the estrogen-protection orthodoxy, empirical research has flourished into the role of androgens in the progression of cardiovascular disease, highlighting the need to better understand androgen receptor (AR) coregulators, nongenomic androgen effects, tissue-specific metabolic activation of androgens, and androgen sensitivity Novel therapeutic targets may arise from understanding how androgens enhance early plaque formation and cause vasodilatation via nongenomic androgen effects on vascular smooth muscle, and how tissue-specific variations in androgen effects are modulated by AR coregulators as well as metabolic activation of testosterone to amplify (via 5alpha-reductase to form dihydrotestosterone acting on AR) or diversify (via aromatization to estradiol acting upon estrogen receptor alpha/beta) the biological effects of testosterone on the vasculature Observational studies show that blood testosterone concentrations are consistently lower among men with cardiovascular disease, suggesting a possible preventive role for testosterone therapy, which requires critical evaluation by further prospective studies Short-term interventional studies show that testosterone produces a modest but consistent improvement in cardiac ischemia over placebo, comparable to the effects of existing antianginal drugs By contrast, testosterone therapy has no beneficial effects in peripheral arterial disease but has not been evaluated in cerebrovascular disease Erectile dysfunction is most frequently caused by pelvic arterial insufficiency due to atherosclerosis, and its sentinel relationship to generalized atherosclerosis is insufficiently appreciated The commonality of risk factor patterns and mechanisms (including endothelial dysfunction) suggests that the efficacy of antiatherogenic therapy is an important challenge with the potential to enhance men's motivation for prevention and treatment of cardiovascular diseases

Non-genomic actions of sex steroid hormones

Abstract: Steroid hormone receptors have been traditionally considered to act via the regulation of transcriptional processes, involving nuclear translocation and binding to specific response elements, and ultimately leading to regulation of gene expression. However, novel non-transcriptional mechanisms of signal transduction through steroid hormone receptors have been identified. These so-called ‘nongenomic’ effects do not depend on gene transcription or protein synthesis and involve steroid-induced modulation of cytoplasmic or cell membrane-bound regulatory proteins. Several relevant biological actions of steroids have been associated with this kind of signaling. Ubiquitous regulatory cascades such as mitogen-activated protein kinases, the phosphatidylinositol 3-OH kinase and tyrosine kinases are modulated through non-transcriptional mechanisms by steroid hormones. Furthermore, steroid hormone receptor modulation of cell membrane-associated molecules such as ion channels and Gprotein-coupled receptors has been shown. Tissues traditionally considered as ‘non-targets’ for classical steroid actions are instead found to be vividly regulated by non-genomic mechanisms. To this aim, the cardiovascular and the central nervous system provide excellent examples, where steroid hormones induce rapid vasodilatation and neuronal survival via non-genomic mechanisms, leading to relevant pathophysiological consequences. The evidence collected in the past years indicates that target cells and organs are regulated by a complex interplay of genomic and non-genomic signaling mechanisms of steroid hormones, and the integrated action of these machineries has important functional roles in a variety of pathophysiological processes. The understanding of the molecular basis of the rapid effects of steroids is therefore important, and may in the future turn out to be of relevance for clinical purposes.

Effect of the environment on the secondary metabolic profile of Tithonia diversifolia : a model for environmental metabolomics of plants

Abstract: Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant's metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts.