Dietary arginine and N-carbamylglutamate supplementation enhances the antioxidant statuses of the liver and plasma against oxidative stress in rats

Abstract

N-Carbamylglutamate (NCG), an effective precursor of arginine (ARG), can enhance ARG synthesis, increase intestinal growth, and improve reproductive performance. However, the antioxidant effect of NCG remains largely unknown. This study aims to survey the effects of ARG and NCG supplementation on the antioxidant statuses of the liver and plasma in rats under oxidative stress. Rats were fed for 30 days with one of the three iso-nitrogenous diets: basal diet (BD), BD plus 1% ARG, and BD plus 0.1% NCG. On day 28, half of the rats fed with BD were intraperitoneally injected with 12 mg per kg body weight of diquat (diquat group) and the other half was injected intraperitoneally with sterile 0.9% NaCl solution (control group). The other diet groups also received an intraperitoneal injection of 12 mg per kg body weight of diquat, as follows: diquat + 1% ARG (DT + ARG), and diquat + 0.1% NCG (DT + NCG). Rat liver and plasma samples obtained 48 h after diquat injection were analyzed. Results indicated that diquat significantly affected the plasma conventional biochemical components (relative to the controls), which were partially alleviated in both the DT + ARG and DT + NCG groups (P < 0.05). Diquat also significantly decreased the glutathione (GSH) content (by 30.0%), and decreased anti-superoxide anion (ASA; by 13.8%) and anti-hydroxyl radical (AHR; by 38.9%) abilities in the plasma, and also decreased catalase (CAT) activity both in the liver (by 17.5%) and plasma (by 33.4%) compared with the control group. By contrast, diquat increased the malondialdehyde (MDA) content (by 23.0%) in the plasma (P < 0.05) compared with the control group. Relative to those of the diquat group, higher CAT activity and GSH content were noted in the plasma of the DT + ARG group and in the liver of both DT + ARG and DT + NCG groups (P < 0.05). Furthermore, the DT + ARG group exhibited significantly enhanced plasma ASA activity (P < 0.05). The DT + NCG group showed significantly improved total antioxidant capacity (T-AOC) in the liver and plasma (P < 0.05). Increased GSH content and elevated ASA and AHR activities were also found, but the MDA content in the plasma was depleted (P < 0.05). Compared with the DT + ARG group, the DT + NCG group showed increased liver and plasma T-AOC, enhanced plasma AHR activity, increased liver ASA activity, and decreased plasma MDA content (P < 0.05). Overall, supplementation of 1% ARG and 0.1% NCG can partially protect the liver and plasma from oxidative stress. Furthermore, compared with 1% ARG, 0.1% NCG more effectively alleviated oxidative stress.

Dietary Supplementation of L-Arginine and N-Carbamylglutamate Attenuated the Hepatic Inflammatory Response and Apoptosis in Suckling Lambs with Intrauterine Growth Retardation

“…Our results suggested that L-Arg or NCG supplementation alleviated the liver function impairment in IUGR lambs as indicated by the decreased serum activity of AST and ALT following Arg or NCG supplementation. The dietary supplementation of L-Arg or NCG has been shown to decrease the AST and ALT levels in rats under oxidative stress [51]. According to our findings, the proinflammatory cytokine concentrations in plasma (IL-1β, TNF-α, and IL-6) were markedly elevated in IUGR suckling lambs, and the plasma levels showed a consistent trend with their respective gene expression identified in this research.…”

“…The adverse effects of IUGR on the above indices of liver growth were mitigated by the L-Arg and NCG supplementation as indicated by improving the protein : DNA ratio. Previous studies highlighted the protective effect of L-Arg against hepatic cell apoptosis [50,51] probably through the upregulation of the Bcl-2 antiapoptotic gene [52]. The IUGR-induced increase in hepatocyte apoptosis was further confirmed by the upregulated Bax and Fas expression; enhanced caspase-3, 8, and 9 activities; and elevated mitochondrial cytochrome C level, as well as the downregulated Bcl-2 expression in the liver of IUGR suckling lambs of our study.…”

Short communication: Effects of dietary addition of N-carbamoylglutamate on milk composition in mid-lactating dairy cows

“…The linearly increased Pro concentration in plasma following the increased NCG addition could be attributed to the Pro synthesis from Arg in the small intestine (Bertolo et al, 2003). As a kind of functional AA, Arg has many functions, including improvement of the production of animals and modulation of the related metabolism (Wu et al, 2004;Cao et al, 2016;. Our study suggested that linearly increased NCG addition improved milk protein content, which is consistent with our previous work (Chacher et al, 2014).…”

“…In Chacher et al (2014), the cows at early-stage lactation produced 40 kg/d of milk, which may be associated with severe oxidative stress due to the high metabolism rate at this stage (Lohrke et al, 2004). In nonruminant animals, Arg is thought to be insufficient under oxidative stress, and it can alleviate oxidative stress responses by improving antioxidative status (Cao et al, 2016). It is possible that Arg is insufficient for the dairy cows under the experimental conditions of Chacher et al (2014).…”

l-Arginine Enhances Resistance against Oxidative Stress and Heat Stress in Caenorhabditis elegans

“…l -Arg concentration directly determines the activity of arginase, the production of NO, urea, citrulline and ornithine [12]. Moreover, l -Arg is also implicated in insulin resistance [13,14], heat stress [15], oxidative stress [16], and many other environmental stresses. These physiological functions of l -Arg may be attributed to its regulating effects on some aging or resistance associated genes.…”