MO342ADMINISTRATION OF ASTRAGALUS MEMBRANACEUS PREVENTED CISPLATIN-INDUCED AKI, ESPECIALLY IN OLD MICE
Authors: Kajiwara Kagemasa , Arai Makoto , Nogami Tatsuya , Nakada Yoshinobu , Nagashima Go , Tashiro Kyoka , Kinue Takaaki 
Published: May 2021

Background and Aims

Recent findings suggest that acute kidney injury (AKI), which occurs frequently but is believed to be completely reversible, is an important factor driving chronic kidney disease (CKD) pathogenesis or progression. We have investigated Astragalus membranaceus (AM), which has been shown to have various pharmacological effects on several organs (see http://nccih.nih.gov/health/astragalus). However, up to now, little evidence of its effectiveness against CKD has been provided. We hypothesized that AM could target AKI and that sustainable prevention of AKI by AM might delay pathogenesis and progression of CKD. Here we focused on AKI as a promoter of CKD progression in order to examine the effects of AM histologically and histochemically in mice.

Method

Here we used two groups of female C57BL/6 mice: one that was aged 12 weeks and one that was aged 52 weeks. After the first blood collection (of approximately 0.2 ml), the two age groups of mice were administered AM powder mixed with sterilized 0.5% methylcellulose 400 (w/v) (the AM-administered group) or sterilized 0.5% methylcellulose 400 (the control group), respectively. Two hours after the administration, 0.5 mg/ml cisplatin (20 mg/kg or 14 mg/kg) or 0.9% NaCl were injected intraperitoneally. Three days after injection, blood was collected and kidneys were harvested. We measured blood urea nitrogen (BUN) and creatinine (CRE) to detect AKI, and assessed histological change in dissected kidney sections stained with Hematoxylin-Eosin and Periodic acid-Schiff and histochemical change in sections stained with anti-CD3 and anti-CD68 antibodies. Generally, 20 mg/kg cisplatin was used to induce AKI in the experimental model.

Results

Injection with 20 mg/kg cisplatin was shown to induce AKI pathology in young mice and shorten survival in old mice, and AM administration was unable to improve AKI pathology in young mice or survival in old mice. Next, we injected mice in both age groups with 14 mg/kg cisplatin. We found that this dose significantly increased serum BUN or CRE and caused histological damage in renal tubule epithelial cells and glomeruli in old mice but not in young mice, which showed no pathological change. And Astragalus treatment in advance almost totally prevented these pathological changes in old mice. The AKI generated in old mice with 14 mg/kg of cisplatin was significantly normalized by pretreatment with AM. Next, histochemical analysis of renal CD3- and CD68-positive cells revealed both were increased in the murine AKI model induced by injection with 20 mg/kg cisplatin. Interestingly, in old mice, 14 mg/kg cisplatin-AKI increased CD3-positive cells but not CD68-positive cells. These findings suggest that AM may improve daily minor disturbances, such as AKI, that cause pathogenesis and progression of CKD especially in old age.

Conclusion

AM administration, at least in part, can reduce day-to-day AKI occurrence, but is ineffective in young kidneys. However, sustained use of AM could play a critical role in prolonging the activity of aged kidneys.

Acknowledgments

We thank the Education and Research Support Center, Tokai University, for technical assistance. This work was supported by a grant from the Japan Society for Promotion of Science JSPS KAKENHI KIBAN-C (Grant Number 16K09259) and by Tokai university general research organization grant.