EFFECT OF POTENTIAL PROBIOTICS ON ALLEVIATING CHRONIC KIDNEY DISEASE PROGRESSION USING CISPLATIN-INDUCED LANYU PORCINE MODEL
National Taiwan University, Taipei, Taiwan
Chronic kidney disease (CKD), characterized by a gradual loss of kidney function, is a global health issue that has a substantial impact on affected individuals. The symptoms of CKD are diverse and include uremia syndrome. Hemodialysis (HD) is unable to effectively eliminate protein-bound solutes as opposed to small water-soluble solutes. The accumulation of protein-bound uremic toxins, including p-cresol and indoxyl sulfate (IS), has been suggested to be related to complications and mortality in HD patients. Our previous study clearly demonstrated that the combination of three strains, Pm-1 which includes Lactobacillus plantarum subsp. plantarum, Lb. paracasei subsp. paracasei and Streptococcus salivarius subsp. thermophilus, have the better ability to reduce uremic toxin, indoxyl sulfate (IS) in MRS broth than individual strains. In vivo, we observed that oral administration of Pm-1 in cisplatin-induced acute kidney injury model significantly suppressed the accumulation of IS in the serum.
Since swine shares similar anatomic and physiologic characteristics with humans, in the present study, we developed a cisplatin-induced CKD model using Lanyu pig, a Taiwan indigenous breed, and investigated the effects of Pm-1 on preventing CKD using this model. Eight-month-old Lanyu pigs were oral administrated with either control diet, or Pm-1 in different dosages (1×109 and 1010 CFU/kg) from 90 days before cisplatin injection and throughout the whole experiment period. Cisplatin was injected intravenously via auricular vein for nine consecutive times every two days.
The results indicated that the pigs fed with high dosage of Pm-1 group showed the trend to reduce both creatinine and blood urea nitrogen (BUN) when compared with cisplatin group. The high dosage Pm-1 group also demonstrated the lower incidence of lesions including atrophy, mononuclear inflammation, cell infiltration and interstitial fibrosis in renal tubules in H&E and masson’s trichrome stain. In fecal microbiota, Pm-1 administration group had more Lactobacterium and Bifidobacterium proportion while less Clostridium when compared with cisplatin group. The high dosage Pm-1 group also decreased TNF-α production and increased level of catalase activity in plasma. However, results of IS in the blood showed no difference among treatments. According to the above results, administration of high dose Pm1 could alleviate cisplatin-induced CKD in a porcine model.
The possible mechanisms of Pm-1 action may due to competitive exclusion of pathogenic bacteria, or modulate immune system of the host as it ameliorates inflammation. Other than that, Pm-1 may possess antioxidant properties that resulted in alleviation of oxidative stress which caused by cisplatin administration.
Keywords: Lanyu pig, Cisplatin, Chronic kidney disease, Probiotics, Anti-oxidative
Wang P. (2016). Effect of potential probiotics on alleviating chronic kidney disease progression using cisplatin-induced lanyu porcine model. Conference Proceedings of IPC2016. Paper presented at the International Scientific Conference on Probiotics and Prebiotics, Budapest (p. 123.). IPC2016