In the present study, we investigated the hypolipidemic and hepatoprotective potential of the commercially available crushed Ajwa date seed-extract on the toxicity caused by the atorvastatin in high-fat diet (HFD)-induced hyperlipidemic rats. Male albino rats were divided into two main groups, Group I (normal control) and Group II (HFD); Group II was further divided into four subgroups: Group IIa (HFD control), Group IIb (Atorvastatin: A10)-6 rats were administered with 10 mg/kg atorvastatin daily for 30 days, Group IIc (Ajwa seed extract: AJ)-6 rats were given 1000 mg/kg Ajwa seed extract daily for 30 days, Group IId (AJ + A10)-6 rats were given Ajwa seed extract 1000 mg/kg and Atorvastatin 10 mg/kg daily for 30 days. The data obtained suggested that Ajwa seed extract lowered the serum cholesterol level in HFD rats and demonstrated the hepatoprotective effect in combination with atorvastatin by reducing the levels of ALT and AST. In conclusion, it protected the tissues from the detrimental effects of hyperglycemia and enhanced antioxidant activity. Furthermore, the dose-limiting toxicity of atorvastatin may be reduced if the Ajwa seed extract is incorporated in the current treatment regimens to treat hyperlipidemia in hypercholesteremic individuals.

Introduction: Werner syndrome is a rare genetic disorder; classical Werner syndrome is caused by mutations in the WRN gene. However, recent research has shown that LMNA gene mutations can also cause premature ageing syndromes such as atypical Werner syndrome (AWS). AWS usually manifests as muscular damage, defects in the cardiac conduction system, lipoatrophy, diabetes, atherosclerosis, and premature ageing. Clinical presentation: A 24-year-old man presented with severe abdominal aortic and peripheral artery disease and cerebral haemorrhage. He was prescribed once-daily 20 mg atorvastatin. Another large cerebral haemorrhage occurred 8 months after discharge. Although he underwent minimally invasive intracranial haematoma surgery, paralysis set in. Molecular studies showed a missense mutation within exon 5 (c.898G>C) that caused amino acid aspartate 300 to be replaced by histidine (p.Asp300His) in the LMNA gene. The patient was diagnosed with AWS. Conclusions: Haemorrhagic stroke and progeroid features may be manifestations of LMNA-linked AWS. In such cases, the patient's family history and genetic background should be investigated. WRN and LMNA gene testing of the proband and the immediate family should be considered. This case report provides a deeper understanding of the role of LMNA mutations in AWS.

The removal efficiency of pharmaceuticals in wastewater treatment plants (WWTPs) is variable and some of these compounds pass these plants almost intact and others presenting a removal efficiency close to 100%. Their incomplete removal results in a continuous discharge of pharmaceuticals into the environment. To assess the profile of contamination of influents and effluents over a day, a set of 83 pharmaceuticals were evaluated hourly in a WWTP in Leiria, Portugal. The composite samples of the influent and effluent were also collected. Concentrations varied from <MDL for ketoprofen, clarithromycin, ofloxacin, and diltiazem to 63.97 μg/L for caffeine in the WWTP influent composite sample and <MDL for clarithromycin, bupropion, and diltiazem to 2.01 μg/L for O-desmethylvenlafaxine for effluent composite sample. Concentrations in the range of μg/L were found for hydroxyibuprofen, salicylic acid, d,l-norephedrine, and caffeine in the WWTP influent, and diclofenac, carbamazepine, O-desmethylvenlafaxine in the WWTP effluents. For the samples collected hourly, thirty-eight and twenty-nine pharmaceuticals were detected in at least one WWTP sample. In the WWTP influent the total concentration of detected pharmaceuticals was higher between 15 and 22 h and lower in the period from 23 to 10 h in the morning. In the WWTP effluent, a slight variation was noticed throughout the sampling hours. Carbamazepine, fluoxetine, sertraline, atorvastatin, caffeine, simvastatin, and trazodone were the pharmaceuticals with risk quotient (RQ) >1 in WWTP influents, and carbamazepine, fluoxetine, sertraline the pharmaceuticals with an RQ > 1 in WWTP effluents.

The aim of this study was to evaluate the effects of atorvastatin and simvastatin on behavioral manifestations that followed hyperhomocysteinemia induced by special dietary protocols enriched in methionine and deficient in B vitamins (B6, B9, B12) by means of alterations in anxiety levels in rats. Simultaneously, we investigated the alterations of oxidative stress markers in rat hippocampus induced by applied dietary protocols. Furthermore, considering the well-known antioxidant properties of statins, we attempted to assess their impact on major markers of oxidative stress and their possible beneficial role on anxiety-like behavior effect in rats. The 4-week-old male Wistar albino rats were divided (eight per group) according to basic dietary protocols: standard chow, methionine-enriched, and methionine-enriched vitamins B (B6, B9, B12) deficient. Each dietary protocol (30 days) included groups with atorvastatin (3 mg/kg/day i.p.) and simvastatin (5 mg/kg/day i.p.). The behavioral testing was performed in the open field and elevated plus maze tests. Parameters of oxidative stress (index of lipid peroxidation, superoxide dismutase, catalase activity, glutathione) were determined in hippocampal tissue samples following decapitation after anesthesia. Methionine-load dietary protocols induced increased oxidative stress in rat hippocampus, which was accompanied by anxiogenic behavioral manifestations. The methionine-enriched diet with restricted vitamins B intake induced more pronounced anxiogenic effect, as well as increased oxidative stress compared to the methionine-load diet with normal vitamins B content. Simultaneous administration of statins showed beneficial effects by means of both decreased parameters of oxidative stress and attenuation of anxiety. The results obtained with simvastatin were more convincible compared to atorvastatin.

Left ventricular hypertrophy (LVH) is a pathological characteristic shared by distinct heart disorders. Atorvastatin is employed as a lipid lowering agent and its heart protection effect has been recently reported as well. Thus, the current study attempted to validate the anti-hypertrophy effect of atorvastatin as well as the associated mechanism. Hypertrophic feature was induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using angiotensin II (Ang II). Then the animals and cells were treated with atorvastatin and the effect on cardiac weight and structure as well as cell viability, surface area, and apoptosis was assessed. The mechanism associated with the anti-hypertrophy effect of atorvastatin was further explored by focusing on the AMPK/Foxo1/miR-143-3p axis. The results showed that the administration of atorvastatin significantly suppressed TAC-induced heart weight increase and attenuated cardiac structure deteriorations in rats. In in vitro assays, atorvastatin increased cell viability, and reduced cell surface area and apoptosis in Ang II-treated H9c2 cells. At molecular level, atorvastatin activated AMPK, which further promoted Foxo1 activation and suppressed miR-143-3p level. The key role of AMPK during atorvastatin treatment was further validated by subjecting Ang II-treated H9c2 cells to co-incubation of atorvastatin and Compound C, which blocked the pro-survival and anti-hypertrophy effect of atorvastatin on H9c2 cells. The findings outlined in the current study confirmed the anti-hypertrophy effect of atorvastatin and provided a preliminary explanation on the mechanism associated with the treatment: the protective effect of atorvastatin on myocardium against hypertrophy depended on miR-143-3p inhibition via AMPK and Foxo1 activation.

The aim of the present study was to examine the effects of atorvastatinon p38 phosphorylation and cardiac remodeling after myocardial infarction in rats. A total of 43 rats were randomly divided into the control, sham operation, post-modeling medication (medication) and post-modeling non-medication (non-medication) groups. The control group did not receive any treatment. Anterior descending arteries of the rats in the medication and non-medication groups were ligated, and threading at the anterior descending arteries was conducted for the rats in the sham operation group. Atorvastatin (10 mg/kg) was given daily to the rats in the medication group, and an equivalent amount of normal saline was given daily to the rats in the sham operation group. Four weeks later, the cardiac function, morphological changes in the myocardial cells, and the expression of tumor necrosis factor-α (TNF-α) and p38 in each group was detected. At 4 weeks after treatment, the myocardial infarction size, fibrosis and myocardial necrosis of the rats in the medication group was examined compared with those in the non-medication group (P<0.05). The cardiac function of the rats in the non-medication group was significantly lower than that of the rats in the control and sham groups (P<0.05), while it was obviously elevated in the medication group compared with that in the non-medication group (P<0.05). The expression of TNF-α and phosphorylated p38 of the left ventricle in the non-medication group was higher than that in the control group (P<0.05), while it was obviously reduced in the non-medication group compared with that in the control group (P<0.05). Atorvastatin can improve cardiac remodeling after myocardial infarction in rats, which may be associated with its inhibition of p38 phosphorylation and its decrease of TNF-α expression.

Statins, a class of cholesterol-lowering drugs, are currently investigated for treatment of age-related macular degeneration, a retinal disease. Herein, retinal and serum concentrations of four statins (atorvastatin, simvastatin, pravastatin, and rosuvastatin) were evaluated after mice were given a single drug dose of 60 mg/kg body weight. All statins, except rosuvastatin, were detected in the retina: atorvastatin and pravastatin at 1.6 pmols and simvastatin at 4.1 pmols. Serum statin concentrations (pmol/ml) were 223 (simvastatin), 1,401 (atorvastatin), 2,792 (pravastatin), and 9,050 (rosuvastatin). Simvastatin was then administered to mice daily for 6 weeks at 60 mg/kg of body weight dose. Simvastatin treatment reduced serum cholesterol levels by 18% and retinal content of cholesterol, lathosterol but not desmosterol by 24% and 21%, respectively. The relative contributions of retinal cholesterol biosynthesis and retinal uptake of serum cholesterol to total retinal cholesterol input were changed as well. These contributions were 79% and 21%, respectively, in vehicle-treated mice and 69% and 31%, respectively, in simvastatin-treated mice. Thus, simvastatin treatment lowered retinal cholesterol because a compensatory upregulation of retinal uptake of serum cholesterol was not sufficient to overcome the effect of inhibited retinal biosynthesis. Simultaneously, simvastatin-treated mice had a 2.9-fold increase in retinal expression of Cd36, the major receptor clearing oxidized low-density lipoproteins from Bruch's membrane. Notably, simvastatin treatment essentially did not affect brain cholesterol homeostasis. Our results reveal the statin effect on the retinal and brain cholesterol input and are of value for future clinical investigations of statins as potential therapeutics for age-related macular degeneration.