Influence of carnosine supplementation on disease progression in a rat model of focal segmental glomerulosclerosis

Abstract

In diabetic kidney disease models, carnosine supplementation ameliorates renal pathology, but its influence in other renal pathologies is less explored. Thus, using the transgenic rat TGRNeph-hAT1 with sex-dependent focal segmental glomerulosclerosis, we first tested whether renal expression levels of carnosine system components correlate with disease. Next, we assessed whether carnosine supplementation in male rats improves pathology. In 10-wk-old phenotypically healthy male and female TGRNeph-hAT1 rats, we compared the renal expression of components of the carnosine system by qRT-PCR. Next, male TGRNeph-hAT1 rats were supplemented with carnosine in drinking water for 20 wk. Subsequently, urinary parameters, renal histology, and renal gene expression of renin-angiotensin system components were assessed. Male TGRNeph-hAT1 rats exhibited less renal expression of carnosine synthase 1, oligopeptide transporter 2, and taurine transporter and higher carnosinase 1 expression than female TGRNeph-hAT1 rats at a young age, before disease starts to develop. Male, but not female, TGRNeph-hAT1 rats developed severe albuminuria, glomerular hypertrophy, and focal and segmental glomerulosclerosis on aging. Carnosine supplementation ameliorated the glomerular hypertrophy but did not affect albuminuria, renal fibrosis, and podocyte loss. Moreover, carnosine significantly reduced renin and increased angiotensin-converting enzyme 2 expression within the kidney. Carnosine treatment alleviates glomerular hypertrophy in TGRNeph-hAT1 rats but does not improve other renal pathologies. Although amelioration of glomerular hypertrophy might be explained by changes in renal renin-angiotensin system expression, further studies are warranted to assess causality.NEW & NOTEWORTHY In diabetic kidney disease models, carnosine supplementation ameliorates renal pathology, but its influence in other renal pathologies is less explored. We tested whether renal expression levels of carnosine system components correlate with disease in the model of the transgenic rat TGRNeph-hAT1 with sex-dependent focal segmental glomerulosclerosis and whether carnosine supplementation in male rats improves pathology. Our results provide evidence that carnosine feeding affects the glomerular hypertrophy and renal RAS expression.

Keywords: carnosine; focal segmental glomerulosclerosis; glomerular hypertrophy; renin-angiotensin system.