Abstract
Background and objectivesImpaired renal function in atherosclerotic renovascular disease (ARD) may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR) regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation.MethodsMale rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each) – ARD, or ARD+BBR – according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively.ResultsCompared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS) and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ.ConclusionsWe conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating chronic renal injury in rats with ARD, and that BBR can act against proinflammatory and profibrotic responses through suppression of the NFκB signaling pathway.
Highlights
Chronic kidney injury caused by renovascular diseases would be increased over time in patients with end-stage renal disease (ESRD) [1]
We investigated whether BBR could protect against chronic renal injury in the rat models with hyperlipidemia and unilateral renal artery stenosis
Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each) – atherosclerotic renovascular disease (ARD) rats with or without administration of BBR (Sigma, St Louis, MO, USA) 150 mg/kg per day by gastric gavage, followed by a 12-week hypercholesterolemic diet to feed [5,6]
Summary
Chronic kidney injury caused by renovascular diseases would be increased over time in patients with end-stage renal disease (ESRD) [1]. The mechanisms responsible for renal damage in this disease are being vigorously sought, and effective therapeutic strategies to preserving the kidney are under intense investigation. Evidence has demonstrated that BBR could effectively regulate cholesterol metabolism, inhibit cell proliferation and act against oxidative stress properties [5,6,7,8,9]. We investigated whether BBR could protect against chronic renal injury in the rat models with hyperlipidemia and unilateral renal artery stenosis. Impaired renal function in atherosclerotic renovascular disease (ARD) may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. We hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and suppression of the pathways involved in oxidative stress, inflammation and NFkB activation
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