Tissue-specific expression of senescence biomarkers in spontaneously hypertensive rats: evidence of premature aging in hypertension.

Background: Cellular senescence is an age-related physiological process that contributes to tissue dysfunction and accelerated onset of chronic metabolic diseases including hypertension. Indeed, elevation of blood pressure in hypertension coincides with premature vascular aging and dysfunction. In addition, onsets of metabolic disturbance and osteopenia in patients with hypertension have also been reported. It is possible that hypertension enhances premature aging and causes progressive loss of function in multiple organs. However, the landscape of cellular senescence in critical tissues affected by hypertension remains elusive. Materials and Methods: Heart, liver, bone, hypothalamus, and kidney were collected from spontaneously hypertensive rats (SHR) and age- and sex-matched normotensive Wistar rats (WT) at 6, 12, 24 and 36 weeks of age (n = 10 animals/group). Changes in mRNA levels of senescence biomarkers namely cyclin-dependent kinase (CDK) inhibitors (CDKIs), i.e., Cdkn2a (encoding p16Ink4a) and Cdkn1a (encoding p21cip1) as well as senescence-associated secretory phenotypes (SASPs), i.e., Timp1, Mmp12, Il6 and Cxcl1, were determined. Additionally, bone collagen alignment and hydroxy apatite crystal dimensions were determined by synchrotron radiation small- and wide-angle X-ray scattering (SAXS/WAXS) techniques. Results: Real-time PCR revealed that transcript levels of genes encoding CDKIs and SASPs in the heart and liver were upregulated in SHR from 6 to 36 weeks of age. Expression of Timp1 and Cxcl1 was increased in bone tissues isolated from 36-week-old SHR. In contrast, we found that expression levels of Timp1 and Il6 mRNA were decreased in hypothalamus and kidney of SHR in all age groups. Simultaneous SAXS/WAXS analysis also revealed misalignment of bone collagen fibers in SHR as compared to WT. Conclusion: Premature aging was identified in an organ directly affected by high blood pressure (i.e., heart) and those with known functional defects in SHR (i.e., liver and bone). Cellular senescence was not evident in organs with autoregulation of blood pressure (i.e., brain and kidney). Our study suggested that cellular senescence is induced by persistently elevated blood pressure and in part, leading to organ dysfunction. Therefore, interventions that can both lower blood pressure and prevent cellular senescence should provide therapeutic benefits for treatment of cardiovascular and metabolic consequences.

A combination extract of kaffir lime, galangal, and lemongrass maintains blood lipid profiles, hepatocytes, and liver mitochondria in rats with nonalcoholic steatohepatitis.

Kaffir lime leaves and the rhizomes of galangal and lemongrass are the main ingredients in several Thai foods with desirable medicinal effects. Based on their beneficial activities, this study aimed to indicate the chemical properties and in vivo efficacy of a combination of the herbs at a 1:2:1 ratio in a water extract form. Its volatile constituents were analyzed by gas chromatography coupled with mass spectrometer, which mainly consists of eucalyptol, citronellal, and citral. Clinicohistopathological and electron microscopic studies demonstrated that the extract corrected blood cholesterol, LDL, HDL, and triglyceride levels similarly as simvastatin treatment in association with its antioxidative properties, as indicated by the levels of superoxide dismutase and malondialdehyde in serum and the increment of nuclear factor erythroid 2-related factor 2 levels in hepatocytes. Hepatitis was significantly less severe in rats fed the extract for 14 days than in simvastatin-treated rats. Regarding its immunomodulatory properties, the extract also accelerated hepatic resolution from steatohepatitis during hypercholesterolemia as indicated by the upregulation of vimentin, cytokeratin, and CD206+. Interestingly, liver mitochondria were also preserved in hypercholesterolemic rats treated with the extract in relation to their architecture and the expression of haloacid dehalogenase-like hydrolase domain-containing protein 3 as well as metabolic and energy regulators. Therefore, the study concluded that the water extract of kaffir lime leaves and the rhizomes of galangal and lemongrass has beneficial effects on blood cholesterol, the severity of steatohepatitis, and the maintenance of mitochondrial architecture via its antioxidative and immunomodulatory activities.

Stillbirths in Macaca fascicularis.

BACKGROUND: Stillbirths in non-human primates are a major problem and represent failure of the maternal-fetal-placental unit to maintain normal relationships because of various endogenous, undetermined or environmental factors. METHODS: Records of 236 stillborns and their dams in a Macaca fascicularis colony during a 7-year period were reviewed retrospectively. RESULTS: The 7-year stillbirth incidence was 11.99% (236 stillbirths, 1967 live births). Most (61.02%, n = 144) were of undetermined etiology. Fetal causes included trauma (22.46%, n = 53), fetal pneumonia (0.85%, n = 2) and congenital anomalies (0.42%, n = 1). Maternal causes included dystocia (9.75%, n = 23) and uterine rupture (0.42%, n = 1). Forty-nine placentas were available for histologic evaluation; there was placentitis in five, necrosis in five and placental abruption in two. Most stillbirths occurred close to term. First stillbirths usually occurred in 8- to 12-year-old animals during the first six pregnancies. CONCLUSIONS: Most stillbirths were of undetermined etiology. Fetal trauma was the most common cause.