Abstract

Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD) on chronic aristolochic acid nephropathy (AAN) in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN), the saline-treated group (AAN + vehicle), the normal dose DFD-treated group (AAN + NDFD), the high dose DFD-treated group (AAN + HDFD), and the rosiglitazone treated group (AAN + Rosi). After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD) markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA), mitochondrial membrane potential (MMP), ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

Highlights

  • Natural and alternative medicines are widely used to treat and prevent different kinds of diseases worldwide

  • We investigated whether the Dahuang Fuzi Decoction (DFD) treatment could improve renal function in the chronic Aristolochic acid nephropathy (AAN) model

  • acids I (AA I) caused a significant loss in the kidney function as characterized by elevated levels of blood urea nitrogen (BUN), serum creatinine (Scr), and urinary protein (Upro) compared to the control group

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Summary

Introduction

Natural and alternative medicines are widely used to treat and prevent different kinds of diseases worldwide. These products, when prepared incorrectly, can result in nephrotoxicity. The patient may develop electrolyte abnormalities, proteinuria, acute kidney injury, and chronic kidney disease (CKD). Aristolochic acid nephropathy (AAN) is one of the best-known iatrogenic kidney diseases caused by Aristolochia herbal medications [1]. AAN is a rapidly progressive interstitial nephropathy that can lead to end-stage renal disease. Previous AAN studies have mostly focused on the aristolochic acids- (AA-) induced acute tubular necrosis and acute nephrotoxicity [2]. The pathological mechanisms responsible for chronic AAN are poorly understood

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