#1373 Effect of Astragalus membranaceus normalized acute kidney injury-induced renal conditions corelated with serum carnosine
Authors: Kajiwara Kagemasa , Arai Makoto , Nogami Tatsuya 
Published: May 2024

Abstract

Background and Aims
Astragalus membranaceus (AM) exhibits various pharmacological effects against several diseases, including chronic kidney disease (CKD) (see http://nccih.nih.gov/health/astragalus). We have previously investigated the correlation between AM and acute kidney injury (AKI), which is an important factor causing CKD pathogenesis or progression. Recently, we demonstrated that old mice showed lethality in response to 20 mg/kg cis-diamminedichloroplatinum (CDDP), which is a general dose used to generate AKI in young mice. AKI also occurred in response to a reduced dose of cisplatin, which was completely reversible in young mice. The administration of AM to mice (20 mg/kg) significantly improved AKI pathology, especially in old mice treated with a reduced dose of cisplatin, thereby demonstrating the therapeutic effect of AM against age-dependent AKI pathogenicity. More recently, we found that serum carnosine levels correlated with renal conditions in AM. Here, we examined the effects associated with serum carnosine levels to prevent AKI and delay CKD progression [1].

Methods
Female C57BL/6 mice (52 weeks old) were orally administered either an AM powder mixed with sterilized 0.5% methylcellulose 400 (w/v) (AM group) or only 0.5% methylcellulose 400 (control). Four hours after the most recent dose (20 mg/kg of AM twice a day), 0.5 mg/ml CDDP (reduced dose: 10 mg/kg or 0.9% NaCl for the CG) was injected intraperitoneally into old mice. Subsequently, we measured the blood serum urea nitrogen (BUN) and creatinine (CRE) levels, which are biomarkers of AKI, and assessed histochemical changes in kidney sections stained with anti-CD3 and anti-CD68 antibodies 20 h and 3 d after CDDP injection (n = 6 per group). Thereafter, serum carnosine levels in the samples collected from each sample (n = 6 per group) were determined using a carnosine ELISA kit (Novus, NBP2-75013). Data were analyzed statistically using PRISM software, and statistical significance was set at P = 0.05.

Results
Higher susceptibility to a half CDDP dose in old mice was indicated by increased BUN levels and the histological damage caused to renal tubule epithelial cells and glomeruli; however, no pathological change was observed in younger mice. Histochemical analysis of old mice showed a significant increase in the number of CD3-positive cells following AKI induction; however, AM pretreatment ameliorated these inflammatory conditions. Our recent findings suggest that a correlation exists between the effects of AM and serum carnosine levels. Fig. 1 shows that different serum carnosine levels were observed in old control mice (white box), probably because of age-dependent pathogenesis. However, serum carnosine was concentrated to lower levels after AM administration (orange box), suggesting an age-dependent AM effect. Moreover, owing to the effect of AM on CDDP-AKI, serum carnosine levels changed transiently but significantly in old mice (blue and yellow boxes) within 20 h; this indicates that age-dependent renal conditions were improved by the AM effect and correlated with serum carnosine levels.

Conclusion
AM administration normalizes the renal pathology caused by age-dependent susceptibility to CDDP-AKI; this is particularly true for older mice, wherein serum carnosine is downregulated but concentrated. Serum carnosine can be effective in preventing AKI pathology in old mice, regardless of the AM effects. We believe that AM can prevent age-dependent accumulation of AKI pathology, thereby facilitating CKD progression.