EFFECT OF RENNIN INHIBITORS AND ANGIOTENSIN II RECEPTOR ANTAGONISTS ON LEFT VENTRICULAR HYPERTROPHY IN RENOVASCULAR HYPERTENSIVE RATS

Objective: Left ventricular (LV) hypertrophy involves numerous structural adaptations that may lead to ventricular dysfunction and eventually, heart failure. Particular emphasis is placed on the molecular mechanisms that govern the development of hypertrophy and may lead to maladaptive structural changes resulting in adverse cardiac events. This study investigates the effectiveness of Valsartan (Val) which is an angiotensinII receptor antagonist and Aliskiren (Ali) which is a direct rennin inhibitor in the treatment of cardiac remodeling resulted from renovascular hypertension, particularly left ventricular hypertrophy, and to address the molecular mechanisms underlying them.Methods: 24 male albino rats were randomly divided into 4 main groups (n=6 each), normal control rats (N), hypertensive control rats (HC), Val treated hypertensive rats (Val, 8 mg/kg/day orally) and Ali treated hypertensive rats (Ali, 25 mg/kg/day orally).Results: At the end of 4 weeks HC rats showed enhanced hypertrophic response (higher heart weight/body weight ratio) and dyslipidemia (lower high density lipoprotein "HDL-c" and higher triacyl glycerol "TAG") and a significant deletion of antioxidant enzymes in comparison with N group. The β myosin heavy chain "βMHC", regulator of calcineurin-1 "RCAN1", nuclear factor kappa B "NFκB" and inducible nitric oxide synthase "iNOS" was markedly elevated. While, α myosin heavy chain "αMHC" was markedly decreased as compared with N group. On the other hand Val treated hypertensive rats and Ali treated hypertensive rats showed a significant decrease in heart weight/body weight ratio, improved lipogram pattern and higher levels of antioxidant enzymes. While, cardiac β-MHC, RCAN-1, NFκB and iNOS were significantly decreased as compared with HC group. Both Val treated hypertensive rats and Ali treated hypertensive rats showed a significant increase in α-MHC, compared with HC groupConclusion: The results reported in this study suggested that chronic untreated hypertension induced a pathological hypertrophy. Administration of the Val or Ali individually exerted beneficial effects regarding the improved lipogram pattern and anti-oxidant enzymes levels, as well as cardiac hypertrophy and highlights the role of Val and Ali as a promising therapeutic strategy for hypertension and LV hypertrophy.Â

Prophylactic and curative effects of purslane on bile duct ligation-induced hepatic fibrosis in albino rats(a)(a)Financial support from National Organization for Drug Control and Research, Giza.

Introduction. Hepatic fibrosis is a common pathological process of chronic liver injury. Oxidative stress and inflammation may have prognostic value in disease progression.Objective. To examine the implication of both aforementioned factors in hepatic fibrosis progression and whether, the antioxidant effect of various biological active constituents such as phenolic, flavonoids and fatty acids of purslane hydro-ethanolic extract can represent a potential target for therapy.Methods. Purslane exhibited a considerable antioxidant potential in DPPH assay compared to α-tocopherol. Consequently, the current study was designed to examine the prophylactic and curative effects of purslane extract on bile duct ligation (BDL)-induced liver fibrosis in rats in comparison with silymarin as a reference hepatoprotective agent. Purslane (400 mg/kg/day) or silymarin (50 mg/kg/day) were administered orally for 4 weeks, immediately after surgery in order to evaluate the prophylactic effect and for 3 weeks starting 3 weeks after BDL in order to evaluate the curative effect. BDL significantly increased liver enzymes, total bilirubin (TB) and tumor necrosis factor-alpha (TNF-α) in serum along with malondialdehyde (MDA) in liver tissues.Results. Significant decrease in hepatic antioxidant defense system was noted in BDL-rats. Conversely, administration of purslane reversed all these biochemical parameters which were previously induced by BDL. Considerably, purslane effect was more pronounced in the prophylactic study than that in the curative one.Conclusion. The present work suggested that purslane had prophylactic and curative value on cholestasis-induced liver fibrosis through inhibition of oxidative stress, decreasing the expression of profibrogenic cytokines, collagenolytic activity and activation of hepatic stellate cells

Assessment of anthracyclin-related hyperlipidemia taurine or PDE4 inhibitor during endotoxemia

No Abstract. The Egyptian Journal of Biochemistry and Molecular Biology Vol. 23(1) 2005: 1-1