Evaluation of aging influence on renal toxicity caused by segment‐specific nephrotoxicants of the proximal tubule in rat†

Abstract

Little is known concerning the sensitivity of aged rats to xenobiotics inducing kidney damage. To increase this knowledge, the age-dependent response of the kidney to hexachloro-1 : 3-butadiene (HCBD) or potassium dichromate (chromate) was investigated. Rats were treated at different ages with a single dose of segment-specific nephrotoxicants of the proximal tubule, chosen on the basis of their specificity for S(3) and for S(1)-S(2) segments, respectively. The toxicological impact of these xenobiotics has been evaluated through biochemical and genomic markers, and histopathological investigation of kidney samples. HCBD treatment induced tubular necrosis of the S(3) segment of the proximal tubule associated with changes of toxicological markers unrelated to the age. In contrast, chromate treatment induced an increased kidney damage related to the rat age. In fact, histopathological investigation revealed that at 1 month of age tubular vacuolar degeneration was seen affecting S(1)-S(2) segments of the proximal tubule, whereas at 3 months of age tubular necrosis occurred in the same segments associated with tubular dilation of the distal portions. Consistently, biochemical analysis confirmed a direct correlation among genomic and biochemical marker variability and animal age. Altogether, the results show that during aging there is an increased sensitivity of kidney to chromate but not to HCBD-induced damage and evidence differential age-related selectivity of rats for nephrotoxic compounds. Significance for human risk assessment is discussed.

The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury

“…Structurally, the PT can be divided into three segments (S1, S2, and S3), with the former two segments are grouped as the proximal convoluted tubule and located in the renal cortex while the S3 proximal straight tubule is located in the outer medulla. Although recent studies showed that there are important axial differences in the function of the three segments of the PT [8], the precise role of each PT segment in the pathogenesis of AKI remains unclear [4,[9][10][11]. As such, we will focus the following discussion on the pathogenic role of PT as a whole in AKI without specifying which segment as the dominant site of injury under different circumstances.…”

Hyaline droplet accumulation in kidney of rats treated with hexachloro‐1:3‐butadiene: influence of age, dose and time‐course

“…After a single injection of HCBD at 100 mg kg −1 b.w, the incidence and severity of the degenerative changes affecting the S3 segment did not appear to be influenced by age, as previously described (Zanetti et al ., ). In contrast, HD accumulation in the S1/S2 segments occurred with an age‐related incidence and severity.…”

Integrative investigation of Semen Strychni nephrotoxicity and the protective effect of Radix Glycyrrhizae by a UPLC-MS/MS method based cell metabolomics strategy in HEK 293t cell lysates

“…GS is a very sensitive marker of kidney injury and ATPase plays an important role in material transport, energy transformation and message passing. 34,35 In this study, GS and ATPase were measured to reect the level of cell function. The GS and ATPase levels of cells in SSG were signicantly decreased (similar with PCG) by 78% and 25%, respectively, when compared with those in BG.…”