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Objective To study the protective effect and related mechanisms of short-chain fatty acid sodium acetate on hypoxia/reoxygenation (H/R)-induced injury of human renal tubular epithelial cell line HK2. Methods The H/R model was established, and HK2 cells were incubated with sodium acetate (SA) for 2 h. The survival rate of HK2 cells was detected by CCK8 assay; Enzyme activity kit was used for detection of inflammatory factors, cellular reactive oxygen species and ATP production; Flow cytometry was used to measure mitochondrial membrane potential (MMP) and mitochondrial oxidative stress products (mitoSOX) levels; Electron microscope was used to observe mitochondrial ultrastructural damage; Western blot was used to detected the expression of inflammatory signaling pathway IκB-α/NF-κB and mitochondrial energy disorder signaling pathway AMPK/PGC-1α. Results Compared with the control group, the survival rate of HK2 cells in the H/R group was significantly decreased(P＜0.05); the expression of intracellular ROS, mitoSOX and inflammatory factors was significantly increased(P＜0.05); the ultrastructure of mitochondria was severely damaged, and the content of ATP and MMP was significantly decreased(P＜0.05); it was further found that the protein expression of p-IκB-α and NF-κB-p-P65 was significantly increased while the protein expression of p-AMPK and PGC-1α was significantly decreased(P＜0.05). Compared with H/R group, SA significantly enhanced the survival rate of HK2 cells (P＜0.05); SA inhibited the release of intracellular ROS, mitoSOX and inflammatory factors; SA inhibited mitochondrial ultrastructural damage, decreased ATP and MMP (P＜0.05); SA promoted the expression of p-AMPK and PGC-1α and inhibited the expression of p-IκB-α and NF-κB-p-P65 (P＜0.05). Conclusions Sodium acetate plays a protective role with potential mechanisms of anti-inflammation, anti-oxidative stress, protection of mitochondrial structure and function of HK2 cells induced by H/R through inhibiting IκB-α/ NF-κB and activating AMPK/PGC-1α signal pathway.

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Ferroptosis is a novel form of iron‐dependent cell death that is involved in arsenic‐induced toxicity. Realgar is an arsenic‐containing Chinese medicine, which can result in nephrotoxicity because of long‐term exposure. However, it remains scientifically unknown whether Realgar is an inducer of ferroptosis in the kidney. This study investigated the role of ferroptosis in Realgar‐induced kidney toxicity in mice. ICR mice were exposed to Realgar for 28 days, and HK2 cells were exposed to Realgar in the presence or absence of treatment with ferrostatin‐1, a ferroptosis inhibitor. The ferroptosis‐related indicators were further evaluated. Realgar can cause nephrotoxicity in mice by continuous gavage for 28 days, accompanied by an increase in iron accumulation and reactive oxygen species (ROS). The reduced expression of Slc7A11 and Gpx4 further confirmed the ferroptosis mediated by Realgar. Meanwhile, Realgar disrupted the antioxidant system as evidenced by the formation of ROS leading to the inactivation of antioxidant enzymes. Realgar caused ferroptosis in a dose‐dependent manner, which was significantly reduced by ferrostatin‐1 in HK2 cells. This study revealed that Realgar‐induced ferroptosis triggered nephrotoxicity in mice and provided new clues to elucidate the mechanism of Realgar‐induced nephrotoxicity. This study investigated the mechanism of Realgar‐induced nephrotoxicity. To the best of our knowledge, this work was the first to prove Realgar caused ferroptosis in a dose‐dependent manner in vivo and in vitro, accompanied by a disruption of the antioxidant system, which provided new clues to elucidate the mechanism of Realgar‐induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Copyright of Modern Food Science & Technology is the property of Editorial Office of Modern Food Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To investigate the effects and mechanism of rehmannioside A (ReA) on diabetic nephropathy (DN) progression. Methods: Various concentrations of glucose and ReA were added to HK2 cells, and cell viability was analyzed using the 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenytetrazoliumromide (MTT) assay. Cell apoptosis, caspase 3 activity, and expression levels of BAX, Bcl-2, and cleaved poly (ADP-ribose) polymerase were evaluated to assess the effect of ReA on cell apoptosis. The effect of ReA on oxidative stress was also evaluated by assessing superoxide dismutase, catalase, and malondialdehyde levels. Lactate dehydrogenase release and reactive oxygen species levels were also measured. Finally, activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 was determined by immunoblot technique. Results: ReA significantly enhanced the survival of HK2 cells induced with high glucose (HG). In addition, ReA suppressed apoptosis and inhibited oxidative stress of HK2 cells induced with HG (p < 0.05). ReA protected against HG-induced apoptosis and oxidative stress of renal tubular epithelial cells by inhibiting the MAPK pathway (p < 0.05). Conclusion: ReA is a potential as a therapeutic agent for DN; however, in vivo and clinical investigations are required to validate this assertion. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) endangers health and is a high financial public burden worldwide. Risk of DN is positively correlated with high levels of reactive oxygen species (ROS). Carnosine, an antioxidant, actively regulates cell function and has the potential to reduce the occurrence of DN. Here, we explored whether carnosine could prevent oxidative stress in human kidney tubular epithelial (HK2) cells and, if so, the mechanisms underlying this effect. HK2 cells were cultured with the ROS hydrogen peroxide (H 2 O 2) for 24 h and then treated with carnosine. In H 2 O 2 -damaged HK2 cells, carnosine significantly increased cell viability, assessed using a Cell Counting Kit 8, increased total superoxide dismutase (T-SOD) activity, assessed using a T-SOD activity detection kit, but decreased ROS levels, assessed using a ROS-sensitive fluorescent probe. Western blotting analyses to determine the protein expression levels of BAX, BCL-2, caspase 3, and the NADPH oxidase isoforms NOX2 and NOX4, as well as confocal laser scanning microscopy to assess changes in the mitochondrial membrane potential and the relative position of mitochondria to cytochrome c , indicated that carnosine inhibited apoptosis via the mitochondrial pathway in H 2 O 2 -damaged HK2 cells. Significantly decreased NOX4 expression and increased T-SOD activity in the presence of carnosine reduced the production of intracellular ROS, relieving oxidative stress to inhibit apoptosis via the mitochondrial pathway. These findings provide molecular mechanistic insights underlying the effects of carnosine, particularly as a potential therapeutic in DN. • Significantly decreased NOX4 expression in the presence of carnosine. • Significantly increased T-SOD activity in the presence of carnosine. • Confocal laser scanning microscopy to assess changes in the mitochondrial membrane potential. • Confocal laser scanning microscopy used to localize the distribution of cytochrome c. [ABSTRACT FROM AUTHOR]

Drug encapsulation in nanocarriers such as polymeric nanoparticles (Nps) may help to overcome the limitations associated with cannabinoids. In this study, the authors' work aimed to highlight the use of electrospraying techniques for the development of carrier Nps of anandamide (AEA), an endocannabinoid with attractive pharmacological effects but underestimated due to its unfavourable physicochemical and pharmacokinetic properties added to its undesirable effects at the level of the central nervous system. The authors characterised physicochemically and evaluated in vitro biological activity of anandamide/ɛ‐polycaprolactone nanoparticles (Nps‐AEA/PCL) obtained by electrospraying in epithelial cells of the human proximal tubule (HK2), to prove the utility of this method and to validate the biological effect of Nps‐AEA/PCL. They obtained particles from 100 to 900 nm of diameter with a predominance of 200–400 nm. Their zeta potential was −20 ± 1.86 mV. They demonstrated the stable encapsulation of AEA in Nps‐AEA/PCL, as well as its dose‐dependent capacity to induce the expression of iNOS and NO levels and to decrease the Na+ /K+ ATPase activity in HK2 cells. Obtaining Nps‐AEA/PCL by electrospraying would represent a promising methodology for a novel AEA pharmaceutical formulation development with optimal physicochemical properties, physical stability and biological activity on HK2 cells. [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the crucial pathogenic factors involved in the progression of renal injury. Angiotensin (ANG) 1–7, a bioactive heptapeptide of the renin-angiotensin-aldosterone system is known to exert antioxidant and nephroprotective effects. However, the cellular mechanism involved in the beneficial effect of ANG 1–7 is not clear. Here, we assessed ANG 1–7′s effect on H 2 O 2 -mediated oxidative damage in the human proximal tubular (HK2) cells and the underlying mechanisms. HK2 cells were incubated with H 2 O 2 (500 µM, 4 h) pre-treated with and without ANG 1–7 (100 nM, 24 h), and reactive oxygen species (ROS) generation, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, apoptosis and mammalian target of rapamycin (mTOR) signaling were determined H 2 O 2 induced an increase in oxidative and ER stress together with loss of mitochondrial membrane potential, decreased ATP levels, and induced apoptosis in HK2 cells. Moreover, H 2 O 2 treatment resulted in the activation of mTOR complexes (mTORC1 and mTORC2) in these cells. ANG 1–7 significantly attenuated H 2 O 2 -induced ROS generation, ER stress and apoptosis, and also improved mitochondrial function. Additionally, pre-treatment of ANG 1–7 inhibited the H 2 O 2 -mediated mTOR activation. These effects of ANG 1–7 were blocked by co-treatment with the Mas receptor (MasR) inhibitor, A779. Furthermore, transfection of HK2 cells with Mas receptor siRNA also abolished the inhibitory effect of ANG 1–7 on mTOR activities. In conclusion, ANG 1–7 via MasR mitigates oxidative stress, suppresses mTOR signaling, and protects HK2 cells from ER stress, mitochondrial dysfunction, and apoptosis, suggesting ANG 1–7-MasR renoprotective effects. [Display omitted] • ANG 1-7 protects HK2 cells against H 2 O 2 -induced oxidative damage and cellular apoptosis. • H 2 O 2 exposure triggers the activation of mTOR complexes (mTORC1 and mTORC2) in HK2 cells. • ANG 1-7 pre-treatment inhibited the H 2 O 2 -induced mTOR activation. • The renoprotective effect of ANG 1-7 is Mas receptor dependent. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The flower of Abelmoschus manihot (Linn.) Medicus ( A. manihot), as a traditional Chinese Herbal medicine, was used widely in China with efficacy of inducing diuresis for treating strangurtia, and subdhing swelling and detoxicating. It has been reported that Huangkui capsule, prepared by the extract of the flower of A. manihot , can reduce the content of urinary protein, serum creatinine and serum urea nitrogen in nephropathy rats and processes renoprotective activity, while the action mechanism need to illuminate deeply. Aims of the study In this study, we investigated the protection effect of Huangkui capsule on tubulointerstitial fibrosis in chronic renal failure (CRF) rats and its mechanism against high glucose-induced epithelial to mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2) of its bioactive components. Materials and methods The animals were divided into normal group, CRF model group and Huangkui capsule-treated group. Hematoxylin eosin (HE) staining and Masson staining were applied to observe pathological changes in renal tissue of different groups. Biochemical indicators including serum urea nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured according to the manufacturer's instructions of kits. HK-2 cell damaged model was established to access the protection effect and action mechanism of five main flavonoids from Huangkui capsule. The experimental cells were divided into eight groups: control group, model group, positive drug group and five main flavonoids treated groups. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to determine the reactive oxygen species (ROS) in different groups. Western blot was applied to analyze the expression of pathogenesis-related proteins in different groups. Results The results stated that Huangkui capsule significantly inhibited the elevation of Scr, BUN, UP, the expression of α-smooth muscle actin (α-SMA), phosphorylation-extracellular signal-regulated kinase (p-ERK1/2), NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in adenine-induced CRF rats. The main bioactive components of quercetin (QT), hyperoside (HY), isoquercitrin (IQT), gossypetin-8- O - β -D-glucuronide (GG) and quercetin-3′- O -glucoside (QG) at the dosage of 100 µM, like NADPH oxidase inhibitor diphenyleneiodonium, exhibited a significant effect on inhibiting the expression of α-SMA, p-ERK1/2, NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in high glucose-induced HK-2 cells, especially GG. Conclusions These results demonstrated that Huangkui capsule and the flavonoids components prevent tubulointerstitial fibrosis in CRF rat involvement in the action mechanism of inhibiting NADPH oxidase/ROS/ERK pathway. [ABSTRACT FROM AUTHOR]

Enzymes of the cytochrome P450 (CYP) super-family are implicated in cadmium (Cd) −induced nephrotoxicity, however, direct evidence is lacking. This study investigated the endogenous expression of various CYP proteins together with the stress-response proteins, heme oxygenase-1 (HO-1) and metallothionein (MT) in human kidney sections and in cadmium-exposed primary cultures of human proximal tubular epithelial cells (PTC). By immunohistochemistry, the CYP members 2B6, 4A11 and 4F2 were prominently expressed in the cortical proximal tubular cells and to a lesser extent in distal tubular cells. Low levels of CYPs 2E1 and 3A4 were also detected. In PTC, in the absence of Cd, CYP2E1, CYP3A4, CYP4F2 and MT were expressed, but HO-1, CYP2B6 and CYP4A11 were not detected. A range of cadmium concentrations (0–100 μM) were utilized to induce stress conditions. MT protein was further induced by as little as 0.5 μM cadmium, reaching a 6-fold induction at 20 μM, whereas for HO-1, a 5 μM cadmium concentration was required for initial induction and at 20 μM cadmium reached a 15-fold induction. The expression of CYP2E1, CYP3A4, and CYP4F2 were not altered by any cadmium concentrations tested at 48 h. Cadmium caused a reduction in cell viability at concentrations above 10 μM. In conclusion although cultured PTC, do express CYP proteins, (CYP2E1, CYP3A4, and CYP4F2), Cd-induced cell stress as indicted by induction of HO-1 and MT does not alter expression of these CYP proteins at 48 h. [ABSTRACT FROM AUTHOR]

In the normal condition, endogenous formation of peroxynitrite ( ONOOˉ) from the interaction of nitric oxide and superoxide has been suggested to play a renoprotective role. However, the exact mechanism associated with renoprotection by this radical compound is not yet clearly defined. Although ONOOˉ usually inhibits renal tubular Na+K+ ATPase ( NKA) activity at high concentrations (micromolar to millimolar range [ μM-mM], achieved in pathophysiological conditions), the effects at lower concentrations (nanomolar range [nM], relevant in normal condition) remain unknown. To examine the direct effect of ONOOˉ on NKA activity, preparations of cellular membrane fraction from mouse renal tissue and from cultured HK2 cells (human proximal tubular epithelial cell lines) were incubated for 10 and 30 min each with different concentrations of ONOOˉ (10 nmol/L-200 μmol/L). NKA activity in these samples ( n = 5 in each case) was measured via a colorimetric assay capable of detecting inorganic phosphate. At high concentrations (1-200 μmol/L), ONOOˉ caused dose-dependent inhibition of NKA activity (−3.0 ± 0.6% and −36.4 ± 1.4%). However, NKA activity remained unchanged at 100 and 500 nmol/L ONOOˉ concentration, but interestingly, at lower concentrations (10 and 50 nmol/L), ONOOˉ caused small but significant increases in the NKA activity (3.3 ± 1.1% and 3.1 ± 0.6%). Pretreatment with a ONOOˉ scavenger, mercaptoethylguanidine ( MEG; 200 μmol/L), prevented these biphasic responses to ONOOˉ. This dose-dependent biphasic action of ONOO− on NKA activity may implicate that this radical compound helps to maintain sodium homeostasis either by enhancing tubular sodium reabsorption under normal conditions or by inhibiting it during oxidative stress conditions. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) remains one of the greatest challenges of urological oncology and is the third leading cause of death in genitourinary cancers. Surgery may be curative when patients present with localized disease. Our previous results demonstrated the autofluorescence of blood PpIX in primary RCC mouse model and an increase in fluorescence intensity as a function of growth of the subcutaneous tumor mass. In another work, a nice correlation between the growth of the tumor mass and tissue fluorescence intensity was found. The aim of this study was to evaluate the expression profile of porphyrin biosynthesis pathway-related genes of human kidney cells. We used two kidney cell lines, one normal (HK2) and another malignant (Caki-1). Endogenous and 5-aminolevolinic acid (ALA) induced protoporphyrin IX (PpIX) HK2 and Caki-1 cells were analyzed by fluorescence spectroscopy. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure mRNA of those genes. Emission spectra were obtained by exciting the samples at 405 nm. For ALA untreated cells the maximum fluorescence intensity was detected at 635 nm. The mean peak area of emission spectra in both cells types increased linearly in function of cell number. Besides, basal levels of PpIX autofluorescence of each cell concentration of HK2 samples were significantly lower than those of Caki-1 samples. For ALA-treated cells the mean PpIX spectra shows PpIX emission peak at 635 nm with a shoulder at 700 nm. Analysis of PpIX fluorescence intensity ratio between tumor cells and HK2 cells showed that fluorescence intensity was, on average, 26 times greater in tumor cells than in healthy cells. qRT-PCR revealed that in Caki-1 ALA-treated cells, PEPT gene was significantly up-regulated and FECH and HO-1 genes were significantly down regulated in comparison with HK2 ALA-treated cells. In conclusion, our results demonstrate the preferential accumulation of ALA-induced PpIX in human RCC and also indicate that PEPT1, FECH and HO-1 genes are major contributors to this accumulation. [ABSTRACT FROM AUTHOR]

Recent studies have identified that high glucose-induced renal tubular cell damage. We previously demonstrated that high glucose treatment induced oxidative stress in human renal proximal tubular epithelial cells (RPTECs), and angiotensin II type 1 (AT1) receptor blockers reduce high glucose-induced oxidative stress in RPTEC possibly via blockade of intracellular as well as extracellular AT1 receptor. However, exact roles of tumor necrosis factor (TNF)-α and AT1 receptor on high glucose-induced renal tubular function remain unclear. N-acetyl-beta-glucosaminidase (NAG), concentrations of TNF-α/angiotensin II and p22phox protein levels after high glucose treatment with or without AT1 receptor blocker or thalidomide, an inhibitor of TNF-α protein synthesis, were measured in immortalized human renal proximal tubular epithelial cells (HK2 cells). AT1 receptor knockdown was performed with AT1 receptor small interfering RNA (siRNA). High glucose treatment (30 mM) significantly increased NAG release, TNF-α/angiotensin II concentrations in cell media and p22phox protein levels compared with those in regular glucose medium (5.6 mM). Candesartan, an AT1R blocker, showed a significant reduction on high glucose-induced NAG release, TNF-α concentrations and p22phox protein levels in HK2 cells. In addition, significant decreases of NAG release, TNF-α concentrations and p22phox protein levels in HK2 cells were observed in high glucose-treated group with thalidomide. AT1R knockdown with siRNA markedly reversed high glucose, angiotensin II or TNF-α-induced p22phox protein levels in HK2 cells. TNF-α may be involved in high glucose-induced renal tubular damage in HK2 cells possibly via AT1 receptor signaling. [ABSTRACT FROM AUTHOR]

Erbin, a member of Leucine-rich repeat and PDZ-containing protein family, was found to inhibit TGF-β-induced epithelial-mesenchymal transition (EMT) in our previous study. However, the mechanism of Erbin in regulating EMT is unclear. Semaphorin protein Sema4C, with PDZ binding site at C-terminal has been recognized as a positive regulator of EMT. Here, we aimed to examine the interaction between Erbin and Sema4C. HK2 cells were treated with TGF-β1, or transfected with Erbin and (or) Sema4C. Interaction of Erbin and Sema4C was identified by immunoprecipitation. RT-PCR was used to detect the expression of Erbin and Sema4C at mRNA level after transfection. The expression levels of Erbin, Sema4C, and markers of EMT were measured by using Western blotting or ELISA. After HK2 cells were stimulated with 10 ng/mL TGF-β1 for 72 h, the protein expression levels of Erbin and Sema4C were both up-regulated, and immunoprecipitation results showed Erbin interacted with Sema4C in HK2 cells both at endogenous and exogenous levels. Furthermore, overexpression of Sema4C suppressed E-cadherin, induced vimentin and promoted fibronectin secretion, indicating Sema4C promotes the process of EMT. However, HK2 cells overexpressing Erbin were resistant to Sema4C-induced EMT. In contrast, Erbin specific siRNA promoted EMT induced by Sema4C. Taken together, these results suggest that Erbin can interact with Sema4C, and co-expression of Erbin blocks the process of Sema4C-induced EMT. [ABSTRACT FROM AUTHOR]

Abstract: An understanding of congener specific cellular absorption of PCBs is important to the study of the organ specific body burden of an individual and to their toxic effects. We have previously demonstrated that single PCB congeners induce cytotoxicity, as evidenced by decreased cellular viability and accelerated apoptotic death. There is very little, if any, information available on the differences in toxicity due to the nature of absorption of PCBs in different cells. To obtain such information human liver (HepG2) cells (in medium with 10% FBS) were exposed to 70μM of both PCB-153 (non-coplanar hexachlorobiphenyl) and PCB-77 (coplanar tetrachlorobiphenyl), and human kidney (HK2) cells in serum free medium were exposed to 80 and 40μM of PCB-153 and PCB-77 respectively, according to their LC50 values in these cells. Medium and cells were collected separately at each time interval from 30min to 48h, and PCB concentrations were analyzed in both by GC–MS using biphenyl as an internal standard following hexane:acetone (50:50) extraction. We also performed trypan blue exclusion, DNA fragmentation and fluorescence microscopic studies in assessing cell viability and apoptotic cell death. About 40% of PCB-153 (35μM, 50% of the maximum value) was detected in HepG2 cells within 30min, and it reached its highest concentration at 6h (60μM), concomitant with the PCB depletion in the medium (5μM). For PCB-77, the highest concentrations within the cells were reached at 3h. However, the absorption levels of PCB-153 and PCB-77 in HK2 cells reached their peaks at 3 and 6h respectively. Exposure of human liver and kidney cells to PCB-153 and PCB-77 caused accelerated apoptotic cell death in a time-dependent manner. The studies demonstrated that (1) liver cells initiate the absorption of PCBs much faster than kidney cells; however, the concentration reaches its maximum level much earlier in kidney cells; (2) both PCB-153 and PCB-77 induced enhanced apoptotic death in liver and kidney cells; and (3) kidney cells are more vulnerable to PCBs based on the results of apoptosis and cellular viability, even with almost similar absorption or tissue burden of PCBs. [Copyright &y& Elsevier]

Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) shows high mortality. Hydrogen sulfide (H 2 S) is essential for regulating kidney function. This study explored the role and mechanism of H 2 S in I/R-induced AKI. I/R-induced mouse model and hypoxia/reoxygenation (H/R)-induced HK2 cell model of AKI were established and treated with NaHS (H 2 S donor), MCC950 (NLRP3 inhibitor) or DL-Propargylglycine (PAG, CSE inhibitor). Serum creatinine (Cr) and blood urea nitrogen (BUN) were measured to evaluate kidney function. The pathological changes of kidney tissues were detected. H 2 S level and H 2 S synthetase activity in kidney tissues were detected. Pyroptosis was assessed by pyroptotic cell numbers and pyroptosis-related protein levels determination. HK-2 cell viability and apoptosis were measured. NLRP3 protein level was detected. The role of NLRP3/Caspase-1 was verified in vivo and in vitro after MCC950 or PAG intervention. I/R-induced mice showed elevated levels of serum Cr and BUN, and obvious pathological changes, including severe tubular dilatation, tubular cell swelling, tubular epithelial cell abscission, tubular cell necrosis and inflammatory cell infiltration. H 2 S level and H 2 S synthetase activity were decreased. Increasing the level of H 2 S by NaHS improved the pathological changes of kidney tissues and limited the number of pyroptotic cells. In vitro, NaHS could reverse H/R-induced cell injury. H 2 S suppressed cell pyroptosis and kidney injury via inhibiting the NLRP3/Caspase-1 axis. We highlighted that H 2 S prevented cell pyroptosis via suppressing the NLRP3/Caspase-1 axis, thereby inhibiting I/R-induced AKI. These findings may confer novel insights for the clinical management of I/R-induced AKI. [ABSTRACT FROM AUTHOR]