L-Citrulline Protects Against Glycerol-Induced Acute Renal Failure in Rats

Abstract

There is an increasing evidence that oxidative stress plays an important role in the pathogenesis of rhabdomyolysisinduced acute renal failure (ARF). In this study, protective effects of L-citrulline on glycerol-induced ARF in rats were investigated. Six groups of rats were employed in this study: group 1 served as a control; group 2 was only given glycerol (50%, 10 mL/kg, i.m.); group 3 was given glycerol plus dexamethasone (0.1 mg/kg, i.g.) as positive reference drug, starting at the same time as the glycerol injections; the last three groups were given glycerol plus L-citrulline (300, 600, and 900 mg/kg, i.g.) respectively, starting at the same time as the glycerol injections. The injections of glycerol were only once, and after glycerol injections the i.g. administrations of dexamethasone and L-citrulline were repeated every 24 h for 7 days. After 7 days of glycerol injections, the blood samples and kidney tissues were harvested for future biochemical and pathology analyses. The levels of creatinine (Cr) and urea nitrogen (BUN) in plasma, the content of malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), the activity of total nitric oxide synthase (TNOS), inducible nitric oxide synthase (iNOS), endothelial NO synthase (eNOS), and superoxide dismutase (SOD) were evaluated in kidney tissues. Consequently, administrations of L-citrulline improved an impaired intrarenal oxygenation and kidney function compared with the glycerol group, and prevented the renal oxidative stress damage as well as severe functional and morphological renal deterioration. Therefore, L-citrulline might have potential application in the amelioration of glycerol-induced ARF.

Evaluations of lipid peroxidation and inflammation in short‐term glycerol‐induced acute kidney injury in rats

“…Considering that most reactive oxygen species (ROS) are highly reactive and short‐lived, it is difficult to detect them in biological substances . Therefore, measurement of the end products of lipid peroxidation is one of the most widely accepted approaches for evaluating oxidative damage . 4‐HNE, which is commonly used as a marker of lipid peroxidation, as well as oxidative DNA and/or protein damage, is the major 4‐hydroxyalkenal end product generated by the decomposition of polyunsaturated fatty acids .…”

“…In sepsis‐induced AKI, TNF‐α activates inducible nitric oxide synthase (iNOS), an indicator of inflammation and stress, which lead to excessive nitric oxide (NO) production . The overproduction of iNOS‐derived NO causes kidney tubular injury in glycerol‐induced AKI . Excess NO reacts with superoxide (O 2 − ) to form peroxynitrite (ONOO − ), a presumed source of hydroxyl radicals, thus causing renal tubular damage …”

Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis

“…A previous study suggested that in some cell types, the activity of NO is influenced by the endogenous antioxidant GSH [22]. It is conceivable that GSH activity may be augmented by L-citrulline as it has been shown that pre-treatment with L-citrulline in rodents for seven consecutive days lead to an elevation in the level of GSH [23]. …”

Açai berry extract attenuates glycerol-induced acute renal failure in rats

“…Moreover, Xing et al and Liu et al reported similar results. 19,20 Many therapeutic agents have been recently used as an attempt to prevent renal damage-induced glycerol, e.g. theophylline, 16 ferulic acid 21 and montelukast.…”