The impact of high-dose statin therapy on transendothelial neutrophil migration and serum cholesterol levels in healthy male volunteers

BackgroundHexavalent Chromium (Cr (VI)) compounds are extremely toxic and have been demonstrated to induce nephrotoxicity associated with oxidative stress in humans and animals. The wide environmental distribution of these agents lead to an increase interest of preventive effects of its adverse effects. ObjectivesThe propose of the present study was to determine the potential protective effects of simvastatin (SIMV) on Cr (VI)-induced nephrotoxicity in rat. Materials and MethodsForty-eight adult male Wistar rats (180-220 g BW) were randomly assigned to eight groups (n = 6). Group one received SIMV 20 mg/kg/day. Group two was given vehicle only. Groups three, five and seven received intraperitoneally (i.p) sodium dichromate (Cr (VI)) at doses of 8, 12 and 16 mg/kg body weight. Groups four, six and eight pretreated with the 20 mg/kg SIMV 30 minutes to prior administration of Cr (VI) at doses of 8, 12 and 16 mg/kg, respectively. The experiment repeated for eight consecutive days. Twenty-four hours after the last administration, animals were killed with overdose of sodium pentobarbital. Kidney tissues were excised for measuring malondialdehyde (MDA), glutathione (GSH) and histopathological examination. ResultsChromium induced a dose dependent elevation of MDA and reduction of GSH levels. Histopathological manifestations were observed in Cr (VI)-treated rats. SIMV administration restored Cr (VI) produced biochemical and morphological changes in rat kidney. SIMV decreased MDA values and increased GSH levels in Cr (VI)-treated rats. SIMV clearly reversed the microscopic damage, demonstrating its protective effects against Cr (VI)-induced kidney injury. ConclusionsThis observation suggests that SIMV may have a protective effect against Cr (VI)-induced oxidative stress in rat kidney.

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“…Statins are commonly used for lowering serum cholesterol levels (11). In addition, these agents have antioxidant property (12).…”

Section: Introductionmentioning

confidence: 99%

Simvastatin attenuates chromium-induced nephrotoxicity in rats

Goodarzi¹,

Karami²,

Ahmadizadeh³

2016

J Nephropathol

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“…Statins influence multiple anti-inflammatory pathways; [12][13][14] it may be that stopping statin therapy at a time of hyper-inflammation could cause rebound inflammation and adversely affect patient outcomes. There is also evidence to suggest that statins are able to modulate immune cell function, which could reduce the damaging inflammation associated with organ dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…11 Inhibition of the mevalonate pathway results in reduced production of isoprenoids, which are required for the function of small GTP-ases and therefore essential for innate and adaptive immunity pathways. [12][13][14] Suggested beneficial effects of statins include improved neutrophil function, 15,16 decreased inflammatory cell influx into the lungs, 17 reduced pro-inflammatory cytokine release, 17,18 prevention of T-cell activation 19 and reduction of local and systemic levels of C-reactive protein (CRP). 20 Based on this, preclinical and observational studies have been performed and suggest a benefit in those with infection; however, these findings have not translated to positive outcomes in randomised controlled trials (RCTs) of established severe sepsis or acute respiratory distress syndrome.…”

Section: Introductionmentioning

confidence: 99%

Statin therapy in patients with community-acquired pneumonia

et al. 2017

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Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. There is evidence of an association between improved survival from infection and statin use. The possible benefi cial effects of statins are complicated by the common use of macrolide antibiotics for pneumonia, with current guidance suggesting that concurrent macrolide and statin use is contraindicated. We conducted an observational study of statin use in patients with CAP. Of 2,067 patients with CAP, 30.4% were on statin therapy at admission. Statin users were more likely to survive the admission (p<0.001). In addition, we conducted a survey of doctors and found that knowledge regarding concurrent macrolide and statin use was lacking. These data suggest a potential role of statins in the management of CAP. Further research using high-dose statins is required to assess their safe use in subjects with mild to moderate infections.

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“…We read with interest the article by Kinsella et al published in the European Journal of Clinical Pharmacology in November 2011 [1]. We would like to congratulate the authors for exploring the potential use of high-dose statin therapy as a therapeutic intervention strategy for patients undergoing major surgeries, including cardiac surgery.…”

Section: Sirmentioning

confidence: 93%