ABSTRACT
Background: Cobalt chloride can be used as an agent to stabilize hypoxia inducible factor-1α (HIF-1α) and to imitate hypoxia without low levels of oxygen inside the body. We intended to investigate if there was any regulation of renin expression by HIF-1α. Therefore, we conducted several studies to clarify this possibility starting with the induction of hypoxic mimicry in rats by intra-peritoneal (IP) injection of cobalt chloride (CoCl2) to obtain the levels and pattern of HIF-1α and renin mRNA and protein expression. Methods: Twenty-four rats were randomly divided into four groups, control group and incubation groups 2, 8, and 24 hours after intra-peritoneal injection of 30 mg CoCl2 per kg BW. After the rats were sacrificed, kidneys were excised, weighed and kidney weight compared to BW. Tissue parameters were measured such as RNA concentration, HIF-1α protein by ELISA, and renin mRNA by RT-PCR. Results: Differences between the groups in the ratios of kidney weight to BW and in the concentrations of HIF-1α protein were statistically not significant (p > 0.05). Relative expression of renin mRNA increased markedly starting 8 hours after CoCl2 IP injection (30 times over controls) and further rising until 24 hours (2465 times over controls). Correlation between HIF-1α and renin mRNA by Pearson analysis was strongly positive, but not significant (R = 0.91; p = 0.09). Conclusion: Renin gene regulation in renal hypoxic mimicry strongly correlates with HIF-1α.
Subject(s)
Mice , Kidney , Renin , ChloridesABSTRACT
Background: Amaranthus spinosus and Andrographis paniculata are traditionally used as antimalarial herbs, but the combination of both has not yet been tested. The aim of this study was to determine the schizonticidal anti-malaria effect of a combination in Plasmodium berghei-infected mice. Methods: Male mice (Balb/c strain) weighing 28-30 g, 7-8 weeks old, were randomly devided into 5 groups of 4 animals each. Group A: controls (nil) and 4 treatment groups (B, C, D, and E). Group B: Amarathus 10 mg/kgBW, group C: Andrographis 2 mg/kgBW, group D: combination of Amaranthus + Andrographis 10 mg + 2 mg/kgBW. All treatment with plant extracts was administered orally, once per day for 7 days. Group E was given chloroquine 10 mg/kgBW, once a day orally, for 3 days. Results: The body weigh increased only in group D, hemoglobin concentration increased significantly vs controls (p < 0.05) in treatment groups C, D, and E, and blood schizonticidal activity was seen in all treatment groups, highest at almost 90% in groups D and E. Survival rate was 100% in all groups. Conclusion: The combination of Amaranthus and Andrographis (10 mg + 2 mg/kgBW) exerts the same blood schizonticidal activity as chloroquine 10 mg/kgBW.
Subject(s)
Plasmodium berghei , MiceABSTRACT
Aim This study explored the expression of HIF-1α in hypoxic cardiac muscle in mice, and observed the evidence of apoptosis in hypoxia induced cardiomyocyte. Methods Male Sprague-Dawley rats, were randomized into 7 groups (n= 4 per group): control normoxia group that was exposed to atmospheric oxygen and hypoxia groups that were housed in hypoxic chambers (O2 level 8%) for 1, 3, 7, 14, 21, and 28 days respectively. Animals were sacrificed, hearts were rapidly excised, total RNA was extracted with an mRNA isolation kit and the expression of HIF-1α mRNA was then detected by real-time RT-PCR. Apoptosis was assessed by TUNEL method. Results For rat in hypoxia group, the expression of HIF-1α mRNA in cardiac myocytes was clearly up-regulated compared to the control normoxia group. Further, HIF-1α expression level elevated gradually and reached a peak at 21 days of hypoxia. No cell labeled by the TUNEL method was detected in the control group. Compared with the control group, the apoptotic index was significantly increased in the hypoxia group (P < 0.05). There was no significant correlation between the elevation of HIF-1α mRNA and the elevation of apoptotic index. Conclusion Systemic chronic hypoxia caused the elevation of HIF-1α mRNA and apoptosis in cardiac myocytes.