Determination of the effects of adropin and spexin on inflammatory pathways in adenine induced chronic renal failure

Chronic renal failure (CRF) can be defined as a chronic and progressive loss of kidney function as a result of a reduction in glomerular filtration rate (GFR). CRF is a chronic inflammatory process. Pro-inflammatory cytokines such as IL-1β, IL-6, IL-17A, IL-21 and IL-33 also trigger renal damage, however anti-inflammatory cytokines such as IL-10, IL-13, TGF-β reduce the renal damage by supressing the inflammatory process. Spexin is a neuropeptide involved in the regulation of glucose and lipid metabolism. In addition, it also regulates cardio-renal function. Adropin is a peptide that regulates many pathways associated with glucose and lipid metabolism. It has been noted that these two peptides can regulate pathways associated with inflammation. In light of this information, our study aims to determine the effects of specsin and adropin administration on kidney damage and inflammatory process in adenine-induced CRF model. The CRF model was created by giving adenine solution to Wistar albino rats. Renal function tests were measured with an autoanalyzer. Histopathological changes in the kidney were evaluated by light microscopy after hematoxylene eosin staining. Expression of IL-1β, IL-10, IL-17A, IL-18, IL-21, IL-33, KIM-1, NGAL, TNF-α, TGF-β, TIMP-1 genes in kidney tissue were determined by real time PCR. 24-hour urine volume, serum creatinine, BUN, and urine protein levels increased in the adenine-induced CRF group compared to the control group. In addition, renal damage, TIMP-1 and IL-33 levels increased with the development of CRF. Administration of Adropin reduced 24-hour urine volume and urine protein levels compared to the CRF group. In addition, renal damage, NGAL, TIMP-1, IL-17A and IL-33 levels were reduced by administration of adropin. Similarly, administration of spexin reduced 24-hour urine volume and urine protein levels compared to the CRF group. In addition, the levels of KIM-1, TIMP-1 and IL-33 decreased with the application of spexin. Administration of Adropin+spexin showed effect in reducing levels of renal damage, KIM-1, NGAL, TIMP-1, IL-1β, IL-17A, IL-18, IL-33, TGF-β and TNF-α compared to CRF group. Our results suggest that these peptides may have protective effects on inflammation and kidney damage.