Morphological and histological kidney structure in diabetic rats model treated with ethanol extracts of jengkol fruit peel (Archidendron pauciflorum)

In a long term, diabetes mellitus (DM) leads to nephropathy due to glomerular hyperfiltration. One of the plant used as a diabetic drug by the community in Karangwangi Village, Cianjur Regency, West Java is the fruit peel of jengkol. Therefore, this study aims to determine the effect of the ethanolic extract of Jengkol fruit peel (EEJFP) toward the morphological and histological structure on the kidney of the diabetic rat model. The method adopted was the Randomized Design (CRD) with 6 treatments namely NC (Carboxyl Methyl Cellulose (CMC) 0.5%), PC (CMC 0.5%), Pb (Glibenclamide 5 mg/kg BW), P1, P2, and P3 (EEJFP 385; 770; and 1,540 mg/kg BW) with 4 replications for 14 consecutive days. Furthermore, the induction of diabetes with streptozotocin dose of 60 mg/Kg BW was performed intravenously in experimental animals except for the NC group. The parameters observed include relative weight, morphological, and histological structure of kidney which include glomerular diameter, Bowman space distance, and percentage of proximal tubular cell necrosis. The non-parametric and parametric data were tested by Kruskal Wallis and ANOVA test as well as Duncan's follow-up test, respectively. The results showed that there was no significant difference in the morphological structure of the kidney between treatment groups. Furthermore, the relative weights of kidney in the PC, Pb, P1, and P3 groups were larger and significantly different compared to NC and P2 also, the histological structure showed that the glomerular diameter (65.43 ± 0.7 m), Bowman space distance (4.19 ± 1.7 µm), and the percentage of proximal tubular cell necrosis (24.6 ± 5.5%) at P2 were not significantly different from NC. Based on this results, it was concluded that EEJFP has no effect on the kidney’s morphological structure, however, it decreases its relative weight and repair the kidney’s histological damage of the diabetic rat model with the optimum dose of 770 mg/kg BW.

Lipophagy deficiency exacerbates ectopic lipid accumulation and tubular cells injury in diabetic nephropathy

Autophagy-mediated lipotoxicity plays a critical role in the progression of diabetic nephropathy (DN), but the precise mechanism is not fully understood. Whether lipophagy, a selective type of autophagy participates in renal ectopic lipid deposition (ELD) and lipotoxicity in the kidney of DN is unknown. Here, decreased lipophagy, increased ELD and lipotoxcity were observed in tubular cells of patients with DN, which were accompanied with reduced expression of AdipoR1 and p-AMPK. Similar results were found in db/db mice, these changes were reversed by AdipoRon, an adiponectin receptor activator that promotes autophagy. Additionally, a significantly decreased level of lipophagy was observed in HK-2 cells, a human proximal tubular cell line treated with high glucose, which was consistent with increased lipid deposition, apoptosis and fibrosis, while were partially alleviated by AdipoRon. However, these effects were abolished by pretreatment with ULK1 inhibitor SBI-0206965, autophagy inhibitor chloroquine and enhanced by AMPK activator AICAR. These data suggested by the first time that autophagy-mediated lipophagy deficiency plays a critical role in the ELD and lipid-related renal injury of DN.

Renal effect of severe hypoxia evaluated By NGAL measurements: An in vivo and in vitro study

Purpose: To investigate possible renal damage in healthy men exposed to extreme hypobaric hypoxia, using urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentration as biomarker. The value of NGAL as a biomarker of proximal tubular cell damage under hypoxic conditions was also tested in vitro experiments. Methods: NGAL was assayed in a cohort of air cadets ( n = 16) exposed to hypobaric hypoxia in a hypobaric chamber during their training program. In all subjects, urine creatinine (Cr) and urinary NGAL levels were measured immediately before, 3, and 24 h after hypobaric environment exposure. Three in vitro experiments using proximal tubular cell cultures were also performed to measure NGAL gene expression, NGAL secretion in the culture medium and to evaluate apoptosis under two cycles of hypoxia and reoxygenation. Results: In the in vivo study, geometric means of urinary NGAL/Cr ratio measured 24 h after hypobaric hypoxia in the hypobaric chamber were significantly lower than baseline values (13.4 vs 25.9 ng/mg, p = 0.01). In cell cultures, hypoxia down-regulated NGAL gene expression without significantly changing NGAL secretion in the culture medium. Hypoxia significantly increased the percentage of apoptotic/necrotic cells, especially after the second hypoxia-reoxygenation cycle. Conclusions: Exposure to hypobaric-hypoxic environments does not cause significant and irreversible renal tubular injury in vivo and in vitro, except than in a late stage. The hypoxic insult does not seem to be mirrored by an increase of urinary NGAL in healthy men nor of NGAL gene expression in HK-2 cell culture or secretion in the culture medium in the in vitro conditions reported in the present study.