Evaluation of statins as a new therapy to alleviate chronotropic dysfunction in cirrhotic rats.

AIMS: Liver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP). Therefore, we evaluated the atorvastatin effect on the heart in cirrhotic rats. MATERIALS AND METHODS: Bile duct ligation (BDL) or sham operation performed on male Wistar rats and grouped as cirrhotic; BDL/Saline, BDL/Ator-7d(days) (Atorvastatin 15 mg/kg/day), and BDL/Ator-14d groups, or control; Sham/Saline, Sham/Ator-7d, and Sham/Ator-14d groups. Corrected QT interval (QTc interval), chronotropic responses, serum brain natriuretic peptides (BNP), heart tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and malondialdehyde (MDA) levels were studied along with atrial Ras homolog family member A (RhoA) and endothelial nitric oxide synthase (eNOS) gene expression. KEY FINDINGS: The chronotropic responses decreased in BDL/Saline and increased in BDL/Ator-7d group. The QTc interval, BNP, TNF-α, and MDA levels increased in BDL/Saline and decreased in BDL/Ator-14d group. The Nrf2 level did not change in BDL/Saline and increased in BDL/Ator-14d group. The liver inflammation and fibrosis increased in BDL/Saline and did not affect BDL/Ator-7d and BDL/Ator-14d groups. The RhoA expression was down-regulated in BDL/Saline, BDL/Ator-7d, and BDL/Ator-14d groups. The eNOS expression did not change in BDL/Saline and down-regulated in BDL/Ator-14d group. SIGNIFICANCE: Atorvastatin alleviates the chronotropic hypo-responsiveness and down-regulates the atrial RhoA and eNOS gene expression along with anti-inflammatory, antioxidant, and anti-stress effects in CCM.

Hepaotoprotective and nephroprotective activities of Pistacia integerrima fruit extract in paracetamol intoxicated male rabbits with effect on blood cells count.

The beneficial effects of Pistacia integerrima (PI) fruit methanol extract on some liver and kidney related parameters and blood cells count of paracetamol (PCM) intoxicated male rabbits were studied. Paracetamol intoxication caused remarkable increase in the serum ALT, AST and ALP levels. The PCM intoxicated rabbits that received PI extract orally at doses of 200 mg and 400 mg/kg b.w. /oral/day for 16 days showed significant reduction in serum ALT, AST and ALP levels (P<0.05). Liver microsections from PCM intoxicated rabbits treated with PI fruit methanol extract showed improvement in the liver histoarchitecture. The urine output of PCM intoxicated control rabbits group was significantly lower (P<0.05). The PCM intoxicated rabbits that received PI extract showed significant increase in urine output (P<0.05). The PCM intoxicated rabbits treated with PI extract also showed significant reduction in the levels of serum urea and creatinine (P<0.05). The renal creatinine clearance of PCM rabbits treated with PI extract improved significantly (P<0.05). Microsections of kidneys from PCM intoxicated rabbits treated with PI fruit methanol extract showed improvement in renal histoarchitecture. During this study, PI extract caused no improvement in the RBC count of PCM intoxicated rabbits. However, the extract caused significant increase in WBC and platelets count (P < 0.05) of PCM intoxicated rabbits. From the findings of the present research, it was concluded that oral administration of P. integerrima fruit methanol extract is beneficial for the liver and kidney related biochemical parameters and blood cells count of paracetamol intoxicated male rabbits.