Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet‐Induced Obese Mice

Abstract

Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-α, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury.

Hydrogen sulfide ameliorates chronic renal failure in rats by inhibiting apoptosis and inflammation through ROS/MAPK and NF-κB signaling pathways

“…H 2 S has recently been recognized as an endogenous gaseous signaling molecule, along with nitric oxide and carbon monoxide 8 – 10 , 15 , 28 . A growing body of evidence indicates that H 2 S plays important and complex roles in renal physiological and pathophysiological processes 11 , 13 , 14 .…”

“…The extent of renal interstitial fibrosis (RIF) was scored from 0 to 3 as follows: 0 = absent, 1 = less than 25% of the area, 2 = 25–50% of the area, and 3 = more than 50% of the area. The RIF index was obtained by the following formula: RIF index = (0 ×  n 0 + 1 ×  n 1 + 2 ×  n 2 + 3 ×  n 3)/( n 0 +  n 1 +  n 2 +  n 3) × 100% 28 . All specimens were anonymized and evaluated in a blinded manner.…”

Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study

“…The rats were randomly divided into the following four groups, with six rats per group: control group, rats fed with standard chow; doxorubicin (DR) group, rats in which the DR-induced kidney injury model was established, rats fed with standard chow; DR+NF group, with the establishment of the DR-induced kidney injury model, fed with standard chow plus NF from week 3 onwards; HFD group, rats were fed with a diet containing 60% of its calories in fat. For comparison of the lipidemic status in the kidneys, an HFD was fed to prepare the obese animal model as a positive control in our design, which also presented kidney injury [ 50 ] in tubule-interstitial fibrosis [ 51 ], lysosomal dysfunction and lipotoxicity [ 30 ], glomerulonephropathy, and proximal tubular damage [ 52 ]. To establish the DR-induced kidney injury model, a single injection of DR at a dose of 8.5 mg/kg was administered after weighting the rats.…”

Hydrogen Sulfide Attenuates Renin Angiotensin and Aldosterone Pathological Signaling to Preserve Kidney Function and Improve Exercise Tolerance in Heart Failure

“…To date, no pharmacological therapeutic has been developed to simultaneously target both the failing heart and the injured kidney. Previous studies have reported that H 2 S therapies effectively ameliorated renal dysfunction in several animal models of kidney diseases through differential mechanisms, suggesting that H 2 S-based therapies may be efficacious in treating both the heart and the kidney in HF 14, 38, 41, 42, 43, 44, 45, 46, 47. In consistent with previous literature, we observed that the mice received Control developed type-II cardiorenal syndrome as evidenced by elevated levels of plasma creatinine and renal fibrosis at 18 weeks post TAC (39).…”