RESUMO
Objective To study the toxicological mechanisms of the compatibility application of Sargassum pallidum and Glycyrrhiza uralensis on kidney in rats. Methods Rats were divided into control, Sargassum pallidum (S), Glycyrrhiza uralensis (G), and Sargassum pallidum-Glycyrrhiza uralensis extract (S-G) groups, which were respectively exposed (gavages) for 4 weeks. Then, the levels of blood urea nitrogen (BUN), serum creatinine (Scr), aldosterone, cortisol, and electrolytes in rat serum and pathological sections of kidney were detected. Six active contents of Glycyrrhiza uralensis in kidney of rats were detected by UPLC-TQ/MS method. The expression of HSD11B2 in kidney was detected by Western blotting. Results Compared with the control group, all biochemical indicators of S group had no obvious change. It was found that the level of aldosterone from G group and S-G group was significantly lower than that from control group (P < 0.05, 0.01). In contrast to the control group, S. pallidum-G. uralensis extract led to significantly increased concentration of cortisol, BUN, and Scr in serum (P < 0.05, 0.01). The level of K+ and Cl- in S-G group was significantly lower than that in control group (P < 0.05, 0.01). Pathological examination showed that the G group had mild inflammation infiltration, and a serious inflammatory response accompanied by protein tube was absolved in S-G group. Compared with the G. uralensis extract group, the combination of S. pallidum and G. uralensis significantly raised the concentration of glycyrrhetinic acid (GA) in kidney (P < 0.05).When compared to that of control group, there was an inhibited expression of HSD11B2 in the kidney of L group and S-G group. Moreover, the expression of HSD11B2 in S-G group was markedly higher than that in G group (P < 0.05). Conclusion The toxicity of S-G group was mainly result that increased accumulation of GA, and inhibited the expression of HSD11B2, which resulted the aldosterone-cortisol system disorders.
RESUMO
The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.
A síndrome de excesso aparente de mineralocorticóide (AME) é uma doença autossômica recessiva rara devido à deficiência da enzima 11β-hidroxiesterσide desidrogenase tipo 2 (11beta-HSD2). A enzima 11beta-HSD2 metaboliza o cortisol ativo a cortisona. As mutações no gene HSD11B2, que codifica a enzima, afetam sua atividade levando a um excesso de cortisol, que terá acesso inapropriado ao receptor de mineralocorticóide, competindo com a ligação da aldosterona. O gene HDS11B2 humano está localizado no cromossomo 16q22 e é formado por 5 éxons que codificam uma proteína de 405 aminoácidos. Este relato apresenta os estudos clínicos e moleculares de um paciente brasileiro do sexo masculino que nasceu prematuro depois de uma gestação sob oligodrâmnio. Recebeu o diagnóstico de AME com 26 meses de idade. Seus pais são primos em segundo grau. A caracterização molecular do gene HSD11B2 revelou a mutação p.R186C em homozigose. O paciente descrito é o segundo caso relatado de brasileiro com mutação no gene HSD11B2.